Updated on 2024/03/28

写真a

 
WAKO, Hiroshi
 
Affiliation
Faculty of Social Sciences
Job title
Professor Emeritus
Degree
Dr. of Science ( Waseda University )

Research Experience

  • 1993
    -
    Now

    Waseda University, Professor

  • 1988
    -
    1993

    Waseda University, Assistant Professor

  • 1986
    -
    1988

    Waseda University, Lecturer

  • 1985
    -
    1986

    Juntendo University, Research Assistant

  • 1982
    -
    1985

    Waseda University, Research Assistant

  • 1978
    -
    1981

    Cornell University, Post-doctoral associate

▼display all

Education Background

  •  
    -
    1978

    Waseda University   Graduate School, Division of Science and Engineering   Physics and Applied Physics  

  •  
    -
    1973

    Waseda Universsity   Faculty of Science and Engineering   Department of Physics  

Professional Memberships

  •  
     
     

    The Chem-Bio Informatics Society

  •  
     
     

    Japanese Society for Bioinformatics

  •  
     
     

    Protein Science Society of Japan

  •  
     
     

    The Physical Society of Japan

  •  
     
     

    The Biophysical Society of Japan

Research Areas

  • Biophysics

Research Interests

  • Protein folding, Bioinformatics

 

Papers

  • Dynamic properties of oligomers that characterize low-frequency normal modes

    Hiroshi Wako, Shigeru Endo

    Biophysics and Physicobiology   16 ( 0 ) 220 - 231  2019  [Refereed]

    Authorship:Lead author

    DOI

    Scopus

    2
    Citation
    (Scopus)
  • Normal mode analysis calculation for a full-atom model with a smaller number of degrees of freedom for huge protein molecules

    Shigeru Endo, Hiroshi Wako

    Biophysics and Physicobiology   16 ( 0 ) 205 - 212  2019  [Refereed]

    DOI

    Scopus

  • A study of CDR3 loop dynamics reveals distinct mechanisms of peptide recognition by T-cell receptors exhibiting different levels of cross-reactivity

    Yuko Tsuchiya, Yoshiki Namiuchi, Hiroshi Wako, Hiromichi Tsurui

    Immunology   153 ( 4 ) 466 - 478  2018.04  [Refereed]

     View Summary

    T-cell receptors (TCRs) can productively interact with many different peptides bound within the MHC binding groove. This property varies with the level of cross-reactivity of TCRs
    some TCRs are particularly hyper cross-reactive while others exhibit greater specificity. To elucidate the mechanism behind these differences, we studied five TCRs in complex with the same class II MHC (1Ab)-peptide (3K), that are known to exhibit different levels of cross-reactivity. Although these complexes have similar binding affinities, the interface areas between the TCR and the peptide–MHC (pMHC) differ significantly. We investigated static and dynamic structural features of the TCR–pMHC complexes and of TCRs in a free state, as well as the relationship between binding affinity and interface area. It was found that the TCRs known to exhibit lower levels of cross-reactivity bound to pMHC using an induced-fitting mechanism, forming large and tight interfaces rich in specific hydrogen bonds. In contrast, TCRs known to exhibit high levels of cross-reactivity used a more rigid binding mechanism where non-specific π-interactions involving the bulky Trp residue in CDR3β dominated. As entropy loss upon binding in these highly degenerate and rigid TCRs is smaller than that in less degenerate TCRs, they can better tolerate changes in residues distal from the major contacts with MHC-bound peptide. Hence, our dynamics study revealed that differences in the peptide recognition mechanisms by TCRs appear to correlate with the levels of T-cell cross-reactivity.

    DOI

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    9
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  • Normal mode analysis as a method to derive protein dynamics information from the Protein Data Bank

    Hiroshi Wako, Shigeru Endo

    Biophysical Reviews   9 ( 6 ) 877 - 893  2017.12  [Refereed]

     View Summary

    Normal mode analysis (NMA) can facilitate quick and systematic investigation of protein dynamics using data from the Protein Data Bank (PDB). We developed an elastic network model-based NMA program using dihedral angles as independent variables. Compared to the NMA programs that use Cartesian coordinates as independent variables, key attributes of the proposed program are as follows: (1) chain connectivity related to the folding pattern of a polypeptide chain is naturally embedded in the model
    (2) the full-atom system is acceptable, and owing to a considerably smaller number of independent variables, the PDB data can be used without further manipulation
    (3) the number of variables can be easily reduced by some of the rotatable dihedral angles
    (4) the PDB data for any molecule besides proteins can be considered without coarse-graining
    and (5) individual motions of constituent subunits and ligand molecules can be easily decomposed into external and internal motions to examine their mutual and intrinsic motions. Its performance is illustrated with an example of a DNA-binding allosteric protein, a catabolite activator protein. In particular, the focus is on the conformational change upon cAMP and DNA binding, and on the communication between their binding sites remotely located from each other. In this illustration, NMA creates a vivid picture of the protein dynamics at various levels of the structures, i.e., atoms, residues, secondary structures, domains, subunits, and the complete system, including DNA and cAMP. Comparative studies of the specific protein in different states, e.g., apo- and holo-conformations, and free and complexed configurations, provide useful information for studying structurally and functionally important aspects of the protein.

    DOI

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    40
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    (Scopus)
  • New tools and functions in data-out activities at Protein Data Bank Japan (PDBj)

    Akira R. Kinjo, Gert-Jan Bekker, Hiroshi Wako, Shigeru Endo, Yuko Tsuchiya, Hiromu Sato, Hafumi Nishi, Kengo Kinoshita, Hirofumi Suzuki, Takeshi Kawabata, Masashi Yokochi, Takeshi Iwata, Naohiro Kobayashi, Toshimichi Fujiwara, Genji Kurisu, Haruki Nakamura

    Protein Science   27 ( 1 ) 95 - 102  2017.09  [Refereed]

     View Summary

    © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society The Protein Data Bank Japan (PDBj), a member of the worldwide Protein Data Bank (wwPDB), accepts and processes the deposited data of experimentally determined biological macromolecular structures. In addition to archiving the PDB data in collaboration with the other wwPDB partners, PDBj also provides a wide range of original and unique services and tools, which are continuously improved and updated. Here, we report the new RDB PDBj Mine 2, the WebGL molecular viewer Molmil, the ProMode-Elastic server for normal mode analysis, a virtual reality system for the eF-site protein electrostatic molecular surfaces, the extensions of the Omokage search for molecular shape similarity, and the integration of PDBj and BMRB searches.

    DOI PubMed

    Scopus

    62
    Citation
    (Scopus)
  • Memorial Issue for Professor Nobuhiko Saitô

    Yura Kei, Wako Hiroshi

    Biophysics and Physicobiology   13 ( 0 ) 243 - 243  2016

    DOI CiNii

    Scopus

  • Characterization of protein folding by a Φ-value calculation with a statistical-mechanical model

    Wako Hiroshi, Abe Haruo

    Biophysics and Physicobiology   13 ( 0 ) 263 - 279  2016  [Refereed]

     View Summary

    <p>The Φ-value analysis approach provides information about transition-state structures along the folding pathway of a protein by measuring the effects of an amino acid mutation on folding kinetics. Here we compared the theoretically calculated Φ values of 27 proteins with their experimentally observed Φ values; the theoretical values were calculated using a simple statistical-mechanical model of protein folding. The theoretically calculated Φ values reflected the corresponding experimentally observed Φ values with reasonable accuracy for many of the proteins, but not for all. The correlation between the theoretically calculated and experimentally observed Φ values strongly depends on whether the protein-folding mechanism assumed in the model holds true in real proteins. In other words, the correlation coefficient can be expected to illuminate the folding mechanisms of proteins, providing the answer to the question of which model more accurately describes protein folding: the framework model or the nucleation-condensation model. In addition, we tried to characterize protein folding with respect to various properties of each protein apart from the size and fold class, such as the free-energy profile, contact-order profile, and sensitivity to the parameters used in the Φ-value calculation. The results showed that any one of these properties alone was not enough to explain protein folding, although each one played a significant role in it. We have confirmed the importance of characterizing protein folding from various perspectives. Our findings have also highlighted that protein folding is highly variable and unique across different proteins, and this should be considered while pursuing a unified theory of protein folding.</p>

    DOI CiNii

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    3
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  • Calculation of Free-Energy Profiles, Folding Rates, and Phi-Values by Means of a Simple Statistical-Mechanical Model of Protein Folding

    H. Wako, H. Abe

    Advances in Protein Folding Research/ Nova Science Publisher     19 - 63  2015

  • Normal mode analysis based on an elastic network model for biomolecules in the protein data Bank, which uses dihedral angles as independent variables

    Hiroshi Wako, Shigeru Endo

    Computational Biology and Chemistry   44   22 - 30  2013  [Refereed]

     View Summary

    Abstract We have developed a computer program, named PDBETA, that performs normal mode analysis (NMA) based on an elastic network model that uses dihedral angles as independent variables. Taking advantage of the relatively small number of degrees of freedom required to describe a molecular structure in dihedral angle space and a simple potential-energy function independent of atom types, we aimed to develop a program applicable to a full-atom system of any molecule in the Protein Data Bank (PDB). The algorithm for NMA used in PDBETA is the same as the computer program FEDER/2, developed previously. Therefore, the main challenge in developing PDBETA was to find a method that can automatically convert PDB data into molecular structure information in dihedral angle space. Here, we illustrate the performance of PDBETA with a protein-DNA complex, a protein-tRNA complex, and some non-protein small molecules, and show that the atomic fluctuations calculated by PDBETA reproduce the temperature factor data of these molecules in the PDB. A comparison was also made with elastic-network-model based NMA in a Cartesian-coordinate system. © 2013 Elsevier Ltd. All rights reserved.

    DOI PubMed

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    27
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  • Dynamic features of homodimer interfaces calculated by normal-mode analysis

    Yuko Tsuchiya, Kengo Kinoshita, Shigeru Endo, Hiroshi Wako

    PROTEIN SCIENCE   21 ( 10 ) 1503 - 1513  2012.10  [Refereed]

     View Summary

    Knowledge of the dynamic features of protein interfaces is necessary for a deeper understanding of proteinprotein interactions. We performed normal-mode analysis (NMA) of 517 nonredundant homodimers and their protomers to characterize dimer interfaces from a dynamic perspective. The motion vector calculated by NMA for each atom of a dimer was decomposed into internal and external motion vectors in individual component subunits, followed by the averaging of time-averaged correlations between these vectors over atom pairs in the interface. This averaged correlation coefficient (ACC) was defined for various combinations of vectors and investigated in detail. ACCs decrease exponentially with an increasing interface area and r-value, that is, interface area divided by the entire subunit surface area. As the r-value reflects the nature of dimer formation, the result suggests that both the interface area and the nature of dimer formation are responsible for the dynamic properties of dimer interfaces. For interfaces with small or medium r-values and without intersubunit entanglements, ACCs are found to increase on dimer formation when compared with those in the protomer state. In contrast, ACCs do not increase on dimer formation for interfaces with large r-values and intersubunit entanglements such as in interwinding dimers. Furthermore, relationships between ACCs for intrasubunit atom pairs and for intersubunit atom pairs are found to significantly differ between interwinding and noninterwinding dimers for external motions. External motions are considered as an important factor for characterizing dimer interfaces.

    DOI

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    4
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    (Scopus)
  • Promode-oligomer: Database of normal mode analysis in dihedral angle space for a full-atom system of oligomeric proteins

    Hiroshi Wako, Shigeru Endo

    Open Bioinformatics Journal   6 ( 1 ) 9 - 19  2012  [Refereed]

     View Summary

    The database ProMode-Oligomer (http://promode.socs.waseda.ac.jp/promode_oligomer) was constructed by collecting normal-mode-analysis (NMA) results for oligomeric proteins including protein-protein complexes. As in the ProMode database developed earlier for monomers and individual subunits of oligomers (Bioinformatics vol. 20, pp. 2035-2043, 2004), NMA was performed for a full-atom system using dihedral angles as independent variables, and we released the results (fluctuations of atoms, fluctuations of dihedral angles, correlations between atomic fluctuations, etc.). The vibrating oligomer is visualized by animation in an interactive molecular viewer for each of the 20 lowest-frequency normal modes. In addition, displacement vectors of constituent atoms for each normal mode were decomposed into two characteristic motions in individual subunits, i.e., internal and external (deformation and rigid-body movements of the individual subunits, respectively), and then the mutual movements of the subunits and the movement of atoms around the interface regions were investigated. These results released in ProMode-Oligomer are useful for characterizing oligomeric proteins from a dynamic point of view. The analyses are illustrated with immunoglobulin light- and heavy-chain variable domains bound to lysozyme and to a 12-residue peptide. © Wako and Endo.

    DOI

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    3
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    (Scopus)
  • Ligand-induced conformational change of a protein reproduced by a linear combination of displacement vectors obtained from normal mode analysis

    Hiroshi Wako, Shigeru Endo

    BIOPHYSICAL CHEMISTRY   159 ( 2-3 ) 257 - 266  2011.12  [Refereed]

     View Summary

    The conformational change of a protein upon ligand binding was examined by normal mode analysis (NMA) based on an elastic-network model (ENM) for a full-atom system using dihedral angles as independent variables. Specifically, we investigated the extent to which conformational change vectors of atoms from an apo form to a holo form of a protein can be represented by a linear combination of the displacement vectors of atoms in the apo form calculated for the lowest-frequency m normal modes (m = 1, 2, ..., 20). In this analysis, the latter vectors were best fitted to the former ones by the least-squares method. Twenty-two paired proteins in the holo and apo forms, including three dimer pairs, were examined. The results showed that, in most cases, the conformational change vectors were reproduced well by a linear combination of the displacement vectors of a small number of low-frequency normal modes. The conformational change around an active site was reproduced as well as the entire conformational change, except for some proteins that only undergo significant conformational changes around active sites. The weighting factors for 20 normal modes optimized by the least-squares fitting characterize the conformational changes upon ligand binding for these proteins. The conformational changes sampled around the apo form of a protein by the linear combination of the displacement vectors obtained by ENM-based NMA may help solve the flexible-docking problem of a protein with another molecule because the results presented herein suggest that they have a relatively high probability of being involved in an actual conformational change. (C) 2011 Elsevier B.V. All rights reserved.

    DOI

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    28
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  • Study of Folding/Unfolding Kinetics of Lattice Proteins by Applying a Simple Statistical Mechanical Model for Protein Folding

    H. Wako, H. Abe

    Protein Folding / Nova Science Publisher     349 - 376  2011

  • Prediction of protein motions from amino acid sequence and its application to protein-protein interaction

    Shuichi Hirose, Kiyonobu Yokota, Yutaka Kuroda, Hiroshi Wako, Shigeru Endo, Satoru Kanai, Tamotsu Noguchi

    BMC STRUCTURAL BIOLOGY   10 ( 20 )  2010.07  [Refereed]

     View Summary

    Background: Structural flexibility is an important characteristic of proteins because it is often associated with their function. The movement of a polypeptide segment in a protein can be broken down into two types of motions: internal and external ones. The former is deformation of the segment itself, but the latter involves only rotational and translational motions as a rigid body. Normal Model Analysis (NMA) can derive these two motions, but its application remains limited because it necessitates the gathering of complete structural information.
    Results: In this work, we present a novel method for predicting two kinds of protein motions in ordered structures. The prediction uses only information from the amino acid sequence. We prepared a dataset of the internal and external motions of segments in many proteins by application of NMA. Subsequently, we analyzed the relation between thermal motion assessed from X-ray crystallographic B-factor and internal/external motions calculated by NMA. Results show that attributes of amino acids related to the internal motion have different features from those related to the B-factors, although those related to the external motion are correlated strongly with the B-factors. Next, we developed a method to predict internal and external motions from amino acid sequences based on the Random Forest algorithm. The proposed method uses information associated with adjacent amino acid residues and secondary structures predicted from the amino acid sequence. The proposed method exhibited moderate correlation between predicted internal and external motions with those calculated by NMA. It has the highest prediction accuracy compared to a naive model and three published predictors.
    Conclusions: Finally, we applied the proposed method predicting the internal motion to a set of 20 proteins that undergo large conformational change upon protein-protein interaction. Results show significant overlaps between the predicted high internal motion regions and the observed conformational change regions.

    DOI

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    14
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  • Folding/unfolding kinetics of lattice proteins studied using a simple statistical mechanical model for protein folding, I: Dependence on native structures and amino acid sequences

    Haruo Abe, Hiroshi Wako

    PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS   388 ( 17 ) 3442 - 3454  2009.09  [Refereed]

     View Summary

    The folding/unfolding kinetics of a three-dimensional lattice protein was studied using a simple statistical mechanical model for protein folding that we developed earlier. We calculated a characteristic relaxation rate for the free energy profile starting from a completely unfolded structure (or native structure) that is assumed to be associated with a folding rate (or an unfolding rate). The chevron plot of these rates as a function of the inverse temperature was obtained for four lattice proteins, namely, proteins a1, a2, b1, and b2, in order to investigate the dependency of the folding and unfolding rates on their native structures and amino acid sequences. Proteins a1 and a2 fold to the same native conformation, but their amino acid sequences differ. The same is the case for proteins b1 and b2, but their native conformation is different from that of proteins a1 and a2. However, the chevron plots of proteins a1 and a2 are very similar to each other, and those of proteins b1 and b2 differ considerably. Since the contact orders of proteins b1 and b2 are identical, the differences in their kinetics should be attributed to the amino acid sequences and consequently to the interactions between the amino acid residues. A detailed analysis revealed that long-range interactions play an important role in causing the difference in the folding rates. The chevron plots for the four proteins exhibit a chevron rollover under both strongly folding and strongly unfolding conditions. The slower relaxation time on the broad and flat free energy surfaces of the unfolding conformations is considered to be the main origin of the chevron rollover, although the free energy surfaces have features that are rather complicated to be described in detail here. Finally, in order to concretely examine the relationship between changes in the free energy profiles and the chevron plots, we illustrate some examples of single amino acid substitutions that increase the folding rate. (C) 2009 Elsevier B.V. All rights reserved.

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    10
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  • 2P-041 Roles of individual amino acid residues in folding/unfolding kinetics of lattice proteins studied with a simple statistical mechanical model(Protein:Property,The 47th Annual Meeting of the Biophysical Society of Japan)

    Abe Haruo, Wako Hiroshi

    Seibutsu Butsuri   49   S113  2009

    DOI CiNii

  • 3P-052 Relationship between folding topology and kinetics using a statistical mechanical model for 3D lattice proteins to circular permutants(The 46th Annual Meeting of the Biophysical Society of Japan)

    Abe Haruo, Wako Hiroshi

    Seibutsu Butsuri   48   S135  2008

    DOI CiNii

  • Single amino acid substitutions in lattice proteins using statistical mechanical model for protein folding

    Hiroshi Wako, Haruo Abe

    JOURNAL OF THE PHYSICAL SOCIETY OF JAPAN   76 ( 10 ) 104801  2007.10  [Refereed]

     View Summary

    The folding of lattice proteins with single amino acid substitutions was studied using a statistical mechanical model for protein folding. All possible single amino acid substitutions were analyzed for two different native conformations, and two amino acid sequences foldable to the given native conformation were considered for each native conformation. First, the transition temperature change Delta T-m(xi(i)) with the conformational energy change Delta E(xi(i)) caused by the substitution of the amino acid residue type xi(i) at the i-th residue was examined. Although both Delta E(xi(i)) and Delta Tm(xi(i)) strongly depend on the amino acid sequence (as a result, these two changes for the two proteins with different amino acid sequences foldable to the same native conformation differ considerably from each other), it is indicated that the correlations between Delta E(xi(i)) and Delta T-m(xi(i)) for the given residue i of the two proteins are mainly determined by their native conformations and are less dependent on their amino acid sequences. We classified the residues into three groups according to the coefficient of regression chi(i) of Delta T-m(xi(i)) on Delta E(xi(i)), i.e., the susceptibility of the conformational stability to the amino acid substitutions. Some of the residues in two of the three groups, which have clear correlations between Delta E(xi(i)) and Delta T-m(xi(i)) but have different chi(i)'s, are clustered to form domains in the native conformations. The residues in the third group, in which Delta T-m(xi(i)) is independent of Delta E(xi(i)), are located in the loop and terminal regions. Secondly, phi(eta, xi(i)), which is defined by referring to the Phi value that characterizes the transition state, but into which the progress variable of protein folding eta is introduced in this study, was examined for the mutants described above. It is shown that phi(eta, xi(i)) can reveal the states of individual amino acid residues and characterize their cooperative behaviors not only in the transition state but also at various stages of the folding process.

    DOI

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    7
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  • Statistical mechanical theory of protein conformation and its transition

    Yukio Kobayashi, Hiroshi Wako, Nobuhiko Saito

    JOURNAL OF THE PHYSICAL SOCIETY OF JAPAN   76 ( 7 ) 074802  2007.07  [Refereed]

     View Summary

    The statistical mechanical theory of the structural transitions of proteins is developed in accordance with the island model by considering the hydrophobic interactions and the entropy factors while connecting the two hydrophobic residues. The proteins treated here are apo-alpha-lactalbumin (IB9O), lysozyme (1LZ1), ferrocytochrome c (1CYC), cytochrome c (isozyme 1) (1YCC), chymotrypsin inhibitor 2 (202), and ubiquitin (1UBQ). Among them, according to the experiments, 202 and 1UBQ do not exhibit intermediate structures (two-state model), but others do exhibit intermediate structures that are sometimes termed molten globules (three-state model). The theory related to these facts is given in terms of the island model, specifically IB9O and 1LZ1. The stability or instability of the intermediate structures is explained by the effects of entropy during folding and the amino acid sequence. The intermediate structure is composed of several stable islands, which become unstable during unfolding.

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    6
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  • 2P115 Statistical mechanical analyses of roles of individual amino acid residues in stability and kinetics of folding of 3D lattice proteins(Proteins-stability, folding, and other physicochemical properties,Poster Presentations)

    Abe Haruo, Wako Hiroshi

    Seibutsu Butsuri   47   S141  2007

    DOI CiNii

  • Analyses of simulations of three-dimensional lattice proteins in comparison with a simplified statistical mechanical model of protein folding

    H. Abe, H. Wako

    PHYSICAL REVIEW E   74 ( 1 ) 011913  2006.07  [Refereed]

     View Summary

    Folding and unfolding simulations of three-dimensional lattice proteins were analyzed using a simplified statistical mechanical model in which their amino acid sequences and native conformations were incorporated explicitly. Using this statistical mechanical model, under the assumption that only interactions between amino acid residues within a local structure in a native state are considered, the partition function of the system can be calculated for a given native conformation without any adjustable parameter. The simulations were carried out for two different native conformations, for each of which two foldable amino acid sequences were considered. The native and non-native contacts between amino acid residues occurring in the simulations were examined in detail and compared with the results derived from the theoretical model. The equilibrium thermodynamic quantities (free energy, enthalpy, entropy, and the probability of each amino acid residue being in the native state) at various temperatures obtained from the simulations and the theoretical model were also examined in order to characterize the folding processes that depend on the native conformations and the amino acid sequences. Finally, the free energy landscapes were discussed based on these analyses. (c) 2006 American Institute of Physics.

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  • 1P100 Effect of single amino acid substitutions on kinetic properties of folding studied by a statistical mechanical model of lattice proteins(3. Protein folding and misfolding (I),Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)

    Abe Haruo, Wako Hiroshi

    Seibutsu Butsuri   46 ( 2 ) S171  2006

    DOI CiNii

  • Analyses of simulations of three-dimensional lattice proteins in comparison with a simplified statistical mechanical model of protein folding

    H. Abe, H. Wako

    Physical Review E - Statistical, Nonlinear, and Soft Matter Physics   74 ( 1 )  2006  [Refereed]

     View Summary

    Folding and unfolding simulations of three-dimensional lattice proteins were analyzed using a simplified statistical mechanical model in which their amino acid sequences and native conformations were incorporated explicitly. Using this statistical mechanical model, under the assumption that only interactions between amino acid residues within a local structure in a native state are considered, the partition function of the system can be calculated for a given native conformation without any adjustable parameter. The simulations were carried out for two different native conformations, for each of which two foldable amino acid sequences were considered. The native and non-native contacts between amino acid residues occurring in the simulations were examined in detail and compared with the results derived from the theoretical model. The equilibrium thermodynamic quantities (free energy, enthalpy, entropy, and the probability of each amino acid residue being in the native state) at various temperatures obtained from the simulations and the theoretical model were also examined in order to characterize the folding processes that depend on the native conformations and the amino acid sequences. Finally, the free energy landscapes were discussed based on these analyses. © 2006 The American Physical Society.

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    25
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  • ProMode: a database of normal mode analyses on protein molecules with a full-atom model

    H Wako, M Kato, S Endo

    BIOINFORMATICS   20 ( 13 ) 2035 - 2043  2004.09  [Refereed]

     View Summary

    Motivation: Although information from protein dynamics simulation is important to understand principles of architecture of a protein structure and its function, simulations such as molecular dynamics and Monte Carlo are very CPU-intensive. Although the ability of normal mode analysis (NMA) is limited because of the need for a harmonic approximation on which NMA is based, NMA is adequate to carry out routine analyses on many proteins to compute aspects of the collective motions essential to protein dynamics and function, Furthermore, it is hoped that realistic animations of the protein dynamics can be observed easily without expensive software and hardware, and that the dynamic properties for various proteins can be compared with each other.
    Results: ProMode, a database collecting NMA results on protein molecules, was constructed. The NMA calculations are performed with a full-atom model, by using dihedral angles as independent variables, faster and more efficiently than the calculations using Cartesian coordinates. In ProMode, an animation of the normal mode vibration is played with a free plug-in, Chime (MDL Information Systems, Inc.). With the full-atom model, the realistic three-dimensional motions at an atomic level are displayed with Chime. The dynamic domains and their mutual screw motions defined from the NMA results are also displayed. Properties for each normal mode vibration and their time averages, e.g. fluctuations of atom positions, fluctuations of dihedral angles and correlations between the atomic motions, are also presented graphically for characterizing the collective motions in more detail.

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    47
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  • Application of a statistical mechanical model for protein folding to a three-dimensional lattice protein

    H Abe, H Wako

    JOURNAL OF THE PHYSICAL SOCIETY OF JAPAN   73 ( 5 ) 1143 - 1146  2004.05  [Refereed]

     View Summary

    A statistical mechanical model for protein folding is applied to the three-dimensional lattice protein using a foldable amino acid sequence. The key to the model lies in the concept of its local structure, defined as a continuous region which takes the same local conformation as in the native conformation, and in the assumption of the absence of interactions between local structures. The partition function is precisely calculated for a given native conformation without any adjustable parameters. The model can well reproduce the equilibrium thermodynamic quantities obtained from the simulation.

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    9
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  • Environment-dependent and position-specific frequencies of amino acid occurrences in α-helices

    H. Wako, J. An, A. Sarai

    Chem-Bio Info. J   3 ( 2 ) 58 - 77  2003  [Refereed]

     View Summary

    By using the method to define a local structural motif of proteins by the Delaunay tessellation proposed by Wako and Yamato (Protein Eng. 11, 981-990 (1998)), we analyzed environment-dependent and position-specific frequencies of amino-acid occurrences in α-helices. In that method the three-dimensional structure of a protein molecule is uniquely divided into non-overlapping Delaunay tetrahedrons, each vertex of which is occupied by one of the comprising residues. A code is then assigned to each tetrahedron so as to characterize the local structure containing it. The tetrahedrons located in the interior of the α-helices are assigned 36 kinds of codes. The differences in the codes reflect the existence and absence of four residues surrounding the relevant region of the α-helix. In other words, the environment of the α-helix can be differentiated by these codes. Accordingly, we analyzed the frequencies of amino acid occurrences on each vertex of the tetrahedrons for each of these codes. Such data provide information about possible amino acid substitutions specific to a vertex position (i.e., a position in the α-helix) for a given code (i.e., environment around the α-helix). Furthermore, the principal component analysis was carried out to reveal general features of the amino acid occurrences in the α-helices. In relation to these results, such frequencies at the N- and C-terminals of the α-helix are also discussed.

    DOI CiNii

  • Analysis of protein structural motifs in terms of sets of codes representing local structures

    J. An, H. Wako, A. Sarai

    Molecular Biology   35 ( 6 ) 905 - 910  2001.11  [Refereed]

     View Summary

    An amino acid sequence pattern conserved among a family of proteins is called motif. It is usually related to the specific function of the family. On the other hand, functions of proteins are realized through their 3D structures. Specific local structures, called structural motifs, are considered as related to their functions. However, searching for common structural motifs in different proteins is much more difficult than for common sequence motifs. We are attempting in this study to convert the information about the structural motifs into a set of one-dimensional digital strings, i.e., a set of codes, to compare them more easily by computer and to investigate their relationship to functions more quantitatively. By applying the Delaunay tessellation to a 3D structure of a protein, we can assign each local structure to a unique code that is defined so as to reflect its structural feature. Since a structural motif is defined as a set of the local structures in this paper, the structural motif is represented by a set of the codes. In order to examine the ability of the set of the codes to distinguish differences among the sets of local structures with a given PROSITE pattern that contain both true and false positives, we clustered them by introducing a similarity measure among the set of the codes. The obtained clustering shows a good agreement with other results by direct structural comparison methods such as a superposition method. The structural motifs in homologous proteins are also properly clustered according to their sources. These results suggest that the structural motifs can be well characterized by these sets of the codes, and that the method can be utilized in comparing structural motifs and relating them with function.

    DOI

    Scopus

  • Sampling efficiency of molecular dynamics and Monte Carlo method in protein simulation

    H Yamashita, S Endo, H Wako, A Kidera

    CHEMICAL PHYSICS LETTERS   342 ( 3-4 ) 382 - 386  2001.07  [Refereed]

     View Summary

    Molecular dynamics (MD) and Monte Carlo (MC) method were compared in terms of the sampling efficiency in protein simulations. In the comparison, both methods use torsion angles as the degrees of freedom and the same force field, ECEPP/2. The MC method used here is the force-bias scaled-collective-variable Monte Carlo (SCV MC) [A. Kidera, Int. J. Quant. Chem. 75 (1999) 207], which corresponds to a finite step size extension to Brownian dynamics. It is shown that MD has about 1.5 times larger sampling efficiency. This difference is attributed to the inertia force term in MD, which does not exist in MC. (C) 2001 Elsevier Science B.V. All rights reserved.

  • Analysis of structural motifs of proteins using sets of codes, describing local structures

    J. An, H. Wako, A. Sarai

    Mol. Biol. (Mosk)   35   1056 - 1062  2001  [Refereed]

  • Significance of a two-domain structure in subunits of phycobiliproteins revealed by the normal mode analysis

    H Kikuchi, H Wako, K Yura, M Go, M Mimuro

    BIOPHYSICAL JOURNAL   79 ( 3 ) 1587 - 1600  2000.09  [Refereed]

     View Summary

    Phycobiliproteins are basic building blocks of phycobilisomes, a supra-molecular assembly for the light-capturing function of photosynthesis in cyanobacteria and red algae. One functional form of phycobiliproteins is a trimeric form consisting of three identical units having C-3 symmetry, with each unit composed of two kinds of subunits, the alpha-subunit and beta-subunit. These subunits have similar chain folds and can be divided into either globin-like or X-Y helices domains. We studied the significance of this two-domain structure for their assembled structures and biological function (light-absorption) using a normal mode analysis to investigate dynamic aspects of their three-dimensional structures. We used C-phycocyanin (C-PC) as an example, and focused on the interactions between the two domains. The normal mode analysis was carried out for the following two cases: 1) the whole subunit, including the two domains; and 2) the globin-like domain alone. By comparing the dynamic properties, such as correlative movements between residues and the fluctuations of individual residues, we found that the X-Y helices domain plays an important role not only in the C-3 symmetry assemblies of the subunits in phycobiliproteins, but also in stabilizing the light absorption property by suppressing the fluctuation of the specific Asp residues near the chromophore. Interestingly, the conformation of the X-Y helices domain corresponds to that of a module in pyruvate phosphate dikinase (PPDK). The module in PPDK is involved in the interactions of two domains, just as the X-Y helices domain is involved in the interactions of two subunits. Finally, we discuss the mechanical construction of the C-PC subunits based on the normal mode analysis.

  • Novel method to detect a motif of local structures in different protein conformations

    H Wako, T Yamato

    PROTEIN ENGINEERING   11 ( 11 ) 981 - 990  1998.11  [Refereed]

     View Summary

    In order to detect a motif of local structures in different protein conformations, the Delaunay tessellation is applied to protein structures represented by C-alpha atoms only. By the Delaunay tessellation the interior space of the protein is uniquely divided up into Delaunay tetrahedra whose vertices are the C-alpha atom positions. Some edges of the tetrahedra are virtual bonds connecting adjacent residues' C-alpha atoms along the polypeptide chain and others indicate interactions between residues nearest neighbouring in space. The rules are proposed to assign a code, i.e., a string of digits, to each tetrahedron to characterize the local structure constructed by the vertex residues of one relevant tetrahedron and four surrounding it. Many sets comprised of the local structures with the same code are obtained from 293 proteins, each of which has relatively low sequence similarity with the others, The local structures in each set are similar enough to each other to represent a motif, Some of them are parts of secondary or supersecondary structures, and others are irregular, but definite structures. The method proposed here can find motifs of local structures in the Protein Data Bank much more easily and rapidly than other conventional methods, because they are represented by codes. The motifs detected in this method can provide more detailed information about specific interactions between residues in the local structures, because the edges of the Delaunay tetrahedra are regarded to express interactions between residues nearest neighbouring in space.

  • A comparative study of dynamic structures between phage 434 Cro and repressor proteins by normal mode analysis

    H Wako, M Tachikawa, A Ogawa

    PROTEINS-STRUCTURE FUNCTION AND GENETICS   26 ( 1 ) 72 - 80  1996.09  [Refereed]

     View Summary

    Two DNA binding proteins, Cro and the amino-terminal domain of the repressor of bacteriophage 434 (434 Cro and 434 repressor) that regulate gene expression and contain a helix-turn-helix (HTH) motif responsible for their site-specific DNA recognition adopt very similar three-dimensional structures when compared to each other. To reveal structural differences between these two similar proteins, their dynamic structures, as examined by normal mode analysis, are compared in this paper. Two kinds of structural data, one for the monomer and the other for a complex with DNA, for each protein, are used in the analyses. From a comparison between the monomers it is found that the interactions of Ala-24 in 434 Cro or VaI-24 in 434 repressor, both located in the HTH motif, with residues 44, 47, 48, and 51 located in the domain facing the motif, and the interactions between residues 17, 18, 28, and 32, located in the PITH motif, cause significant differences in the correlative motions of these residues. From the comparison between the monomer and the complex with DNA for each protein, it was found that the first helix in the HTH motif is distorted in the complex form. While the residues in the HTH motif in 434 Cro have relatively larger positive correlation coefficients of motions with other residues within the HTH motif, such correlations are not large in the HTH motif of 434 repressor. It is suggestive to their specificity because the 434 repressor is less specific than 434 Cro, Although a structural comparison of proteins has been performed mainly from a static or geometrical point of view, this study demonstrates that the comparison from a dynamic point of view, using the normal mode analysis, is useful and convenient to explore a difference that is difficult to find only from a geometrical point of view, especially for proteins very similar in structure. (C) 1996 Wiley-Liss, Inc.

  • Conformational analysis of nucleic acid molecules with flexible furanose rings in dihedral angle space

    M Tomimoto, N Go, H Wako

    JOURNAL OF COMPUTATIONAL CHEMISTRY   17 ( 7 ) 910 - 917  1996.05  [Refereed]

     View Summary

    The computational algorithm that works in the coordinate space of dihedral angles (i.e., bond lengths and bond angles are kept fixed and only rotatable dihedral angles are treated as independent variables) is extended to deal with the pseudorotational motion of furanose rings by introducing a variable of pseudorotation. Then, this algorithm is applied to a distance geometry calculation that generates three-dimensional (3D) structures that are consistent with given constraints of interatomic distances. This method efficiently generates 3D structures of an RNA hairpin loop which satisfy a set of experimental NMR data. (C) 1996 by John Wiley & Sons, Inc.

  • New implementation of and the modeling by the extended simulated annealing process to structures of T4 lysozyme mutants at the 86th residue

    S Endo, J Higo, K Nagayama, H Wako

    JOURNAL OF COMPUTATIONAL CHEMISTRY   17 ( 4 ) 476 - 488  1996.03  [Refereed]

     View Summary

    The extended simulated annealing process (ESAP) is a useful method for modeling the partial structure of proteins [J. Higo et al., Biopolymers, 32, 33 (1992)]. In ESAP, a protein molecule is divided into two parts: small, flexible fragments constituting the concerned partial structure, and the remaining part, for which the structure is kept rigid during the simulation. We have improved the program of ESAP so that it can be adapted to general macromolecules. Any sidechain on the rigid part can be set to rotate. Soft repulsion between van der Waals spheres is introduced to avoid conformational trapping into local minima. This improved program was tested for modeling structural changes caused by eight kinds of amino acid mutation at the 86th residue in T4 lysozyme. For each mutant we obtained a model structure that was close to the X-ray structure. The root mean square (rms) deviations from the X-ray structure were 0.3 to 0.8 Angstrom for all heavy atoms and about 0.2 Angstrom for the main-chain atoms. We also modeled the structure of an Ile mutant, for which the X-ray structure has not yet been reported. ESAP can be used to model structural changes due to a single residue mutation in proteins. (C) 1996 by John Wiley & Sons, Inc.

  • FEDER/2 - PROGRAM FOR STATIC AND DYNAMIC CONFORMATIONAL ENERGY ANALYSIS OF MACRO-MOLECULES IN DIHEDRAL ANGLE SPACE

    H WAKO, S ENDO, K NAGAYAMA, N GO

    COMPUTER PHYSICS COMMUNICATIONS   91 ( 1-3 ) 233 - 251  1995.09  [Refereed]

     View Summary

    The computer program, FEDER/2, has been developed to carry out static and dynamic conformational energy analysis of macromolecules by treating dihedral angles as independent variables. The original program, FEDER (ii. Wake and N. GS, J. Comput. Chem. 8 (1987) 625), developed to rapidly calculate first and second derivatives of a conformational energy function with respect to dihedral angles for a single one protein molecule, has been extended by generalizing the tree representation and by revising the program. The tree topology of a molecular system, which is essential to this program, is defined in terms of rigid &apos;unit&apos; and rotatable &apos;bond&apos;. Then, algorithms and formulae based on the tree topology are developed to calculate the first and second derivatives. In this revised version of the program we have constructed a library of units, from which a set of data required for a given specific system of molecules is generated. By separating such parts of the program that take care of specifics of various molecular systems into a form of data in the library of units, the main part of the program to calculate the first and second derivatives has become general enough to be applicable to wider types of molecules.

  • SECONDARY STRUCTURE PREDICTION OF BETA-SUBUNITS OF THE GONADOTROPIN-THYROTROPIN FAMILY FROM ITS ALIGNED SEQUENCES USING ENVIRONMENT-DEPENDENT AMINO-ACID SUBSTITUTION TABLES AND CONFORMATIONAL PROPENSITIES

    H WAKO, S ISHII

    BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY   1247 ( 1 ) 104 - 112  1995.02  [Refereed]

     View Summary

    The secondary structures of beta-subunits of the glycoprotein hormone family, LH (luteinizing hormone), CG (chorionic gonadotropin), FSH (follicle stimulating hormone), TSH (thyroid stimulating hormone), and GTH I/GTH II (two types of fish gonadotropins), are predicted by comparing an amino-acid substitution pattern at equivalent sites in their aligned sequences with environment-dependent amino-acid substitution tables and conformational propensities calculated from other protein families whose three-dimensional structures are known. According to the prediction results, together with other structural information obtained from experiments, the following points come up as important structural features of the beta-subunits of this family; The regions assigned to regular secondary structures (one alpha-helix and three beta-strands) are considered to constitute a core of the beta-subunits. They involve interaction sites with carbohydrate and alpha-subunit. Out of the six disulfide bonds formed in the beta-subunit, four are located together on one side of the core, and the other two on the opposite side. The two regions assumed to be a receptor binding region from experiments (therefore, species-specific regions) are predicted as loops located on the same side of the beta-subunit in this study. Some of the predicted loops are rich in proline residues. While the positions of proline residues are conserved in the family generally, there are hormone- or species-specific ones in the loop that is assumed to take part in receptor binding. The possible importance of proline residues in hormone or species specificity is discussed. (After submitting the manuscript the X-ray crystal structure of human CG was published. In order to evaluate the prediction, the original manuscript is kept intact and a comparison has been made between the prediction results and the crystal structure in an appendix)

  • Dynamic Relationships among Economic Variables Examined by the Embedding Method

    T. Inaba, Y. Nagai, H. Wako

    Dynamical Systems and Chaos (N. Aoki et al. ed.) / World Scientific    1995

  • THE RECOGNITION OF PROTEIN-STRUCTURE AND FUNCTION FROM SEQUENCE - ADDING VALUE TO GENOME DATA

    ACW MAY, MS JOHNSON, SD RUFINO, H WAKO, ZY ZHU, R SOWDHAMINI, N SRINIVASAN, MA RODIONOV, TL BLUNDELL

    PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES   344 ( 1310 ) 373 - 381  1994.06  [Refereed]

     View Summary

    The explosion of DNA sequence data from genome projects presents many challenges. For instance, we must extend our current knowledge of protein structure and function so that it can be applied to these new sequences. The derivation of rules for the relationships between sequence and structure allow us to recognize a common fold by the use of tertiary templates. New techniques enable us to begin to meet the challenge of rule-based modelling of distantly related proteins. This paper describes an integrated and knowledge-based approach to the prediction of protein structure and function which can maximize the value of sequence information.

  • USE OF AMINO-ACID ENVIRONMENT-DEPENDENT SUBSTITUTION TABLES AND CONFORMATIONAL PROPENSITIES IN STRUCTURE PREDICTION FROM ALIGNED SEQUENCES OF HOMOLOGOUS PROTEINS .2. SECONDARY STRUCTURES

    H WAKO, TL BLUNDELL

    JOURNAL OF MOLECULAR BIOLOGY   238 ( 5 ) 693 - 708  1994.05  [Refereed]

  • USE OF AMINO-ACID ENVIRONMENT-DEPENDENT SUBSTITUTION TABLES AND CONFORMATIONAL PROPENSITIES IN STRUCTURE PREDICTION FROM ALIGNED SEQUENCES OF HOMOLOGOUS PROTEINS .1. SOLVENT ACCESSIBILITY CLASSES

    H WAKO, TL BLUNDELL

    JOURNAL OF MOLECULAR BIOLOGY   238 ( 5 ) 682 - 692  1994.05  [Refereed]

  • MOLECULAR-BIOLOGY OF GONADOTROPINS

    S ISHII, H ANDO, H WAKO, Y KUBOTA

    AVIAN ENDOCRINOLOGY     123 - 133  1993  [Refereed]

  • DISTANCE-CONSTRAINT APPROACH TO HIGHER-ORDER STRUCTURES OF GLOBULAR-PROTEINS WITH EMPIRICALLY DETERMINED DISTANCES BETWEEN AMINO-ACID-RESIDUES

    H WAKO, Y KUBOTA

    JOURNAL OF PROTEIN CHEMISTRY   10 ( 2 ) 233 - 243  1991.04  [Refereed]

     View Summary

    An analysis of higher-order structures of globular proteins by means of a distance-constraint approach is presented. Conformations are generated for each of 21 test proteins of small and medium sizes by optimizing an objective function f = SIGMA-SIGMA-w(ij)(d(ij) - &lt;d(ij)&gt;)2, where d(ij) is a distance between residues i and j in a calculated conformation, &lt;d(ij)&gt; is an assigned distance to the (ij) pair of residues which is determined based on the statistics of known three-dimensional structures of 14 proteins in the earlier study, and w(ij) is a weighting factor. &lt;d(ij)&gt; involves information about hydrophobicity and hydrophilicity of each amino acid residue and about connectivity of a polypeptide chain. In these calculations, only the amino acid sequence is used as input data specific to a calculated protein. With respect to higher-order structures regenerated in the optimized conformations, the following properties are analyzed: (a) N14 of a residue, defined as the number of residues surrounding the residue located within a sphere of radius of 14 angstrom; (b) root-mean-square differences of the global and localconformations from the corresponding X-ray conformations; (c) distance profiles in the short and medium ranges; and (d) distance maps. The effects of supplementary information about locations of secondary structures and disulfide bonds are also examined to discuss the potential ability of this methodology to predict the three-dimensional structures of globular proteins.

  • A NEW VERSION OF DADAS (DISTANCE ANALYSIS IN DIHEDRAL ANGLE SPACE) AND ITS PERFORMANCE

    S ENDO, H WAKO, K NAGAYAMA, N GO

    COMPUTATIONAL ASPECTS OF THE STUDY OF BIOLOGICAL MACROMOLECULES BY NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY   225   233 - 251  1991  [Refereed]

  • Protein conformation in terms of conformational energy analysis.

    H. Wako

    Protein Structural Analysis, Folding and Design (H.. Hatano ed.) / Japan Scientific Societies Press and Elsevier     3 - 17  1990

  • MONTE-CARLO SIMULATIONS OF A PROTEIN MOLECULE WITH AND WITHOUT HYDRATION ENERGY CALCULATED BY THE HYDRATION-SHELL MODEL

    H WAKO

    JOURNAL OF PROTEIN CHEMISTRY   8 ( 6 ) 733 - 747  1989.12  [Refereed]

  • DYNAMIC STRUCTURES OF GLOBULAR-PROTEINS WITH RESPECT TO CORRELATIVE MOVEMENTS OF RESIDUES CALCULATED IN THE NORMAL MODE ANALYSIS

    H WAKO

    JOURNAL OF PROTEIN CHEMISTRY   8 ( 5 ) 589 - 607  1989.10  [Refereed]

  • A FRACTAL MODEL OF PROTEIN CONFORMATIONS AND SPECTRAL EXPONENTS FOR THE DENSITIES OF LOW-FREQUENCY NORMAL-MODES OF VIBRATION

    H WAKO

    JOURNAL OF THE PHYSICAL SOCIETY OF JAPAN   58 ( 6 ) 1926 - 1929  1989.06  [Refereed]

  • Inspection of three-dimensionalstructures of proteins with dynamical information from the normal modeanalysis.

    H. Wako

    Protein Seq. Data Anal.   2   175 - 180  1989  [Refereed]

  • ALGORITHM FOR RAPID CALCULATION OF HESSIAN OF CONFORMATIONAL ENERGY FUNCTION OF PROTEINS BY SUPERCOMPUTER

    H WAKO, N GO

    JOURNAL OF COMPUTATIONAL CHEMISTRY   8 ( 5 ) 625 - 635  1987.07  [Refereed]

  • DEVELOPMENT OF SOFTWARE TOOLS FOR PROTEIN-STRUCTURE DESIGN

    H NAKAMURA, T YAMAZAKI, H ABE, T NOGUCHI, Y SENO, H WAKO, N GO

    JOURNAL OF MOLECULAR GRAPHICS   4 ( 3 ) 180 - 181  1986.09  [Refereed]

  • MONTE-CARLO STUDY ON LOCAL AND SMALL-AMPLITUDE CONFORMATIONAL FLUCTUATION IN HEN EGG-WHITE LYSOZYME

    H WAKANA, H WAKO, N SAITO

    INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH   23 ( 3 ) 315 - 323  1984  [Refereed]

  • UNFOLDING OF TERTIARY STRUCTURES OF PROTEINS

    H WAKANA, H YOKOMIZO, H WAKO, Y ISOGAI, K KOSUGE, N SAITO

    INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH   23 ( 6 ) 657 - 670  1984  [Refereed]

  • CIS-TRANS ISOMERIZATION OF PROLINE IN THE PEPTIDE (HIS-105-VAL-124) OF RIBONUCLEASE-A CONTAINING THE PRIMARY NUCLEATION SITE

    MR PINCUS, F GEREWITZ, H WAKO, HA SCHERAGA

    JOURNAL OF PROTEIN CHEMISTRY   2 ( 2 ) 131 - 146  1983  [Refereed]

  • STATISTICAL MECHANICAL TREATMENT OF ALPHA-HELICES AND EXTENDED STRUCTURES IN PROTEINS WITH INCLUSION OF SHORT-RANGE AND MEDIUM-RANGE INTERACTIONS

    H WAKO, N SAITO, HA SCHERAGA

    JOURNAL OF PROTEIN CHEMISTRY   2 ( 3 ) 221 - 249  1983  [Refereed]

  • Hydrophobic interaction and the prediction of the tertiary structures of proteins.

    N. Saito, H. Wako, T. Akutsu, Y. Oyama

    Studies Phys. Theor. Chem.   27   325 - 338  1983

  • VISUALIZATION OF THE NATURE OF PROTEIN FOLDING BY A STUDY OF A DISTANCE CONSTRAINT APPROACH IN TWO-DIMENSIONAL MODELS

    H WAKO, HA SCHERAGA

    BIOPOLYMERS   21 ( 3 ) 611 - 632  1982  [Refereed]

  • Distance-constraint approachto protein folding. I. Statistical analysis of protein conformations interms of distances between residues.

    H. Wako, H.A. Scheraga

    J. Protein Chem.   1   5 - 45  1982  [Refereed]

  • Distance-constraint approachto protein folding. II. Prediction of three-dimensional structure of bovinepancreatic trypsin inhibitor

    H. Wako, H.A. Scheraga

    J. Protein Chem.   1   85 - 117  1982  [Refereed]

  • ON THE USE OF DISTANCE CONSTRAINTS TO FOLD A PROTEIN

    H WAKO, HA SCHERAGA

    MACROMOLECULES   14 ( 4 ) 961 - 969  1981  [Refereed]

  • Statistical mechanical theoryof the protein conformation I. General considerations and the applicationto homopolymers.

    H. Wako, N. Saito

    J. Phys. Soc. Jpn   44   1931 - 1938  1978  [Refereed]

  • Statistical mechanical theoryof the protein conformation II. Folding pathway for protein.

    H. Wako, N. Saito

    J. Phys. Soc. Jpn   44   1939 - 1945  1978  [Refereed]

  • Tertiary structures of gastrin-like tetrapeptides.

    T. Yamada, H. Wako, N. Saito, Y. Isogai, H. Watari

    Int. J. Pept. Protein Res.   8   607 - 614  1976  [Refereed]

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Books and Other Publications

  • Study of Folding/Unfolding Kinetics of Lattice Proteins by Applying a Simple Statistical Mechanical Model for Protein Folding

    H. Wako, H. Abe

    Nova Biomedical  2011.01 ISBN: 9781617619229

  • 科学技術は社会とどう共生するか(分担執筆): 「科学技術ジャーナリストの課題」(パネルディスカッションの記録)

    高橋真理子, 渡部潤一, 輪湖 博, 小山慶太

    東京電機大学出版局  2009.04 ISBN: 9784501624309

  • トポロジーデザイニング 新しい幾何学からはじめる物質・材料設計(分担執筆): 「タンパク質のモチーフ構造解析 」

    輪湖 博

    (株)エヌ・ティー・エヌ  2009.04

  • バイオインフォマティクス事典 (分担執筆): 「構造エネルギー最適化法」「基準振動解析」の項目

    輪湖 博

    共立出版  2006.06

  • 複雑系の構造と予測 (分担執筆): 「タンパク質分子の立体構造転移」

    輪湖 博, 安部晴男

    共立出版  2006.06

  • 物理学辞典三訂版 (分担執筆): 「アンフィンゼンのドグマ」「タンパク質の折りたたみ過程」「ディスタンス・ジオメトリー」の項目

    輪湖 博

    培風館  2005.09

  • 社会人間学 (分担執筆): 「生命倫理学と人間行動」

    那須 政玄, 輪湖 博

    成文堂  1997

  • タンパク質のかたちと物性 (分担執筆): 「タンパク質という複雑系へのアプローチ」

    輪湖 博

    共立出版  1997

  • 時間と変化の経済学 (共訳)

    有賀裕二, 浅田統一郎, 稲葉敏夫, 輪湖 博

    中央大学出版部  1994

  • アイザック・アシモフの科学と発見の年表 (共訳)

    小山慶太, 輪湖 博

    丸善  1992

  • 『Computational Aspects of the Study of Biological Macromolecules by Nuclear Magnetic Resonance Spectroscopy』(分担執筆)、A new version of DADAS(Distance Analysis in Dihedral Angle Space)and its performance(共著)

    Plenum  1991

  • 機能性食品タンパク質工学ハンドブック (分担執筆): 「タンパク質の高次構造と機能-計算化学・計算物理学からのアプローチ」

    輪湖 博

    サイエンスフォーラム  1991

  • 『Protein Structural Analysis, Folding and Design』(分担執筆)、Protein Conformation in terms of conformational energy analysis

    Japan Scientific Societies Press &amp; Elsvier  1990

  • 遺伝情報の科学

    輪湖 博

    成文堂  1990

  • 計算物理学と計算化学 (分担執筆): 「蛋白質の立体構造シミュレーション」(共著)

    輪湖 博, 郷 信広

    海文堂  1988

  • BASICによる生物 (共著)

    荻原利彦, 小林謙三, 永井喜則, 土屋尚, 輪湖 博

    共立出版  1987

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Presentations

  • タンパク質の基準振動モードのネットワーク解析:中心性指標Betweennessと活性部位

    第17回日本蛋白質科学会年会 

    Presentation date: 2017.06

  • タンパク質の基準振動モードのネットワーク解析:中心性指標の計算

    第54回日本生物物理学会年会 

    Presentation date: 2016.11

  • T細胞受容体による特異的および交差反応的な抗原認識機構の解明

    第54回日本生物物理学会年会 

    Presentation date: 2016.11

  • 二面角系基準振動解析プログラムの巨大分子への適用―側鎖自由度の固定

    第16回日本蛋白質科学会年会 

    Presentation date: 2016.06

  • 動的構造解析に基づく特異性および交差性を有するTCRの抗原認識機構の解明

    第16回日本蛋白質科学会年会 

    Presentation date: 2016.06

  • 二面角系基準振動解析プログラムの並列化と巨大分子への適用

    第53回日本生物物理学会年会 

    Presentation date: 2015.09

  • 結晶環境における弾性ネットワークモデルを用いた非等方性温度因子の再現

    第52回日本生物物理学会年会 

    Presentation date: 2014.09

  • PDBETA ver. 2: 弾性ネットワークモデルによる基準振動解析計算のためのGUIアプリケーション

    第14回日本蛋白質科学会年会 

    Presentation date: 2014.06

  • 結晶環境における弾性ネットワークモデルを用いた高分解能X線構造における温度因子の再現

    第51回日本生物物理学会年会 

    Presentation date: 2013.10

  • Ensemble Docking Simulation for β-2 Adrenergic Receptor Using Elastic Network Model

    CBI学会2013年大会 

    Presentation date: 2013.10

  • 基準振動解析に基づくホモダイマー相互作用面の動的な特徴

    第13回日本蛋白質科学会年会 

    Presentation date: 2013.06

  • 弾性ネットワークモデルによる基準振動モードを取り込んだβ2アドレナリンGPCRのアンサンブルドッキングシミュレーション

    第13回日本蛋白質科学会年会 

    Presentation date: 2013.06

  • 結晶中のタンパク質分子に対する2面角系弾性ネットワークモデル

    第13回日本蛋白質科学会年会 

    Presentation date: 2013.06

  • 弾性ネットワークモデルを利用したβ2アドレナリン受容体のアンサンブルドッキング

    第50回日本生物物理学会年会 

    Presentation date: 2012.09

  • リガンド結合に伴う多量体タンパク質の三次構造および四次構造変化の基準振動解析

    第12回 日本蛋白質科学会年会 

    Presentation date: 2012.06

  • 水和自由エネルギーを考慮したタンパク質の弾性ネットワークモデル

    第12回 日本蛋白質科学会年会 

    Presentation date: 2012.06

  • Development and Releasing of New Databases forProtein Dynamics: ProMode-Oligomer and ProMode-Elastic.

    Presentation date: 2011.11

  • Characterization of a conformational change of protein with elastic-network-model based normal mode analysis in dihedral angle space.

    17th International Biophysics Congress 

    Presentation date: 2011.10

  • Conformational change reproduced by a linear combination of displacement vectors obtained from normal mode analysis

    Presentation date: 2011.09

  • 二面角系弾性ネットワークモデルによる基準振動解析:タンパク質−DNA複合体における内部運動と外部運動

    第11回日本蛋白質科学会年会 

    Presentation date: 2011.06

  • 基質結合にともなうタンパク質の構造変化の基準振動解析による再現

    第11回日本蛋白質科学会年会 

    Presentation date: 2011.06

  • ProMode-Elastic: database of elastic-network-model based normal mode analysis

    InCob 2010 

    Presentation date: 2010.09

  • Structure deviation analyses of proteins complexed with various ATP analogs.

    InCob 2010 

    Presentation date: 2010.09

  • ミオシンモータードメインにおけるATP加水分解反応機構の分子軌道法研究

    第48回日本生物物理学会年会 

    Presentation date: 2010.09

  • リング状の5量体タンパク質の基準振動解析

    第48回日本生物物理学会年会 

    Presentation date: 2010.09

  • 二面角系弾性ネットワークモデルによる基準振動解析:DNA 結合タンパク質への適用

    第10回日本蛋白質科学会年会 

    Presentation date: 2010.06

  • 水素結合を考慮したタンパク質の弾性ネットワークモデルの精密化

    第10回日本蛋白質科学会年会 

    Presentation date: 2010.06

  • アミノ酸配列からのタンパク質揺らぎ領域予測と蛋白質間相互作用への適用

    第47回日本生物物理学会年会 

    Presentation date: 2009.10

  • 基準振動に基づく蛋白質・蛋白質相互作用の動的特徴の解析

    第47回日本生物物理学会年会 

    Presentation date: 2009.10

  • フォールディングキネティクスにおけるアミノ酸残基の役割—格子タンパク質に統計力学モデルを適用して—

    第47回日本生物物理学会年会 

    Presentation date: 2009.10

  • 基準振動解析データベースPDBηおよびProMode-Oligomerの開発

    第47回日本生物物理学会年会 

    Presentation date: 2009.10

  • ATP加水分解中のミオシン内残基間距離の相対変化のPDBデータを用いた研究

    第47回日本生物物理学会年会 

    Presentation date: 2009.10

  • 基準振動に基づく蛋白質複合体界面の動的構造の解析

    第9回日本蛋白質科学会 

    Presentation date: 2009.05

  • ATP加水分解におけるミオシンモータードメインの局所構造変化の相関

    日本生物物理学会第46回年会 

    Presentation date: 2008.12

  • タンパク質の主鎖トポロジーとフォールディングキネティクスとの関係—3次元格子タンパク質の円順列変異体に統計力学モデルを適用して

    日本生物物理学会第46回年会 

    Presentation date: 2008.12

  • 二面角系での弾性ネットワークモデルによる基準振動解析の評価

    日本生物物理学会第46回年会 

    Presentation date: 2008.12

  • 基準振動解析における結合モードに基づくタンパク質複合体の動的構造の分類

    日本生物物理学会第46回年会 

    Presentation date: 2008.12

  • コンタクトオーダーとフォールディング速度との関係−3次元格子タンパク質の円順列変異体に統計力学モデルを適用して

    第8回日本蛋白質科学会年会 

    Presentation date: 2008.06

  • 二面角系での弾性ネットワークモデルによる基準振動解析

    第8回日本蛋白質科学会年会 

    Presentation date: 2008.06

  • タンパク質複合体の基準振動における結合モードの解析

    第8回日本蛋白質科学会年会 

    Presentation date: 2008.06

  • アミノ酸配列情報を用いた蛋白質運動性の予測

    第8回日本蛋白質科学会年会 

    Presentation date: 2008.06

  • 蛋白質2分子複合体の基準振動の包括的解析

    日本生物物理学会第45回年会 

    Presentation date: 2007.12

  • ProModeを利用したタンパク質の基準振動解析プログラムの開発

    日本生物物理学会第45回年会 

    Presentation date: 2007.12

  • フォールディンぐの安定性とキネティクスにおけるアミノ酸残基の役割−3次元格子タンパク質に統計力学モデルを適用して

    日本生物物理学会第45回年会 

    Presentation date: 2007.12

  • アミノ酸配列からのタンパク質の構造揺らぎ領域の予測

    日本生物物理学会第45回年会 

    Presentation date: 2007.12

  • ATPアナログ結合ミオシン結晶データのパッチ解析による構造比較

    日本生物物理学会第45回年会 

    Presentation date: 2007.12

  • アミノ酸置換によるファールディング速度の変化−格子タンパク質に統計力学モデルを適用して−

    第7回日本蛋白質科学会年会 

    Presentation date: 2007.05

  • 立体構造不定領域のあるタンパク質の動的構造の解析とデータベースProModeへの取り込み

    第7回日本蛋白質科学会年会 

    Presentation date: 2007.05

  • ProModeユーザーのための基準振動解析プログラムの開発

    第7回日本蛋白質科学会年会 

    Presentation date: 2007.05

  • Effect of single amino acid substitutions on kinetic properties of folding studied by a statistical mechanical model of lattice proteins

    Fifth East Asian Biopyhsics Symposium 

    Presentation date: 2006.11

  • Structural alignment with Delaunay codes characterizing local structures and structural motifs identified by the alignment

    Fifth East Asian Biopyhsics Symposium 

    Presentation date: 2006.11

  • Normal mode analyses of multimeric proteins with symmetry in dihedral angle space

    Fifth East Asian Biopyhsics Symposium 

    Presentation date: 2006.11

  • Dynamic structures of proteins characterized by networks formed by connecting positively correlated residues in normal mode vibrations

    Fifth East Asian Biopyhsics Symposium 

    Presentation date: 2006.11

  • Comparisons between dynamic properties of homologous protein structure in ProMode (Database of normal mode analyses on proteins)

    GIW2005 

    Presentation date: 2005.12

  • 基準振動解析による相同なタンパク質の動的構造の比較

    日本生物物理学会第43回年会 

    Presentation date: 2005.11

  • 異種及び同種2量体タンパク質の基準振動解析

    日本生物物理学会第43回年会 

    Presentation date: 2005.11

  • アミノ酸置換による熱力学量の変化と折れたたみ機構

    第5回日本蛋白質科学会年会 

    Presentation date: 2005.06

  • ドロネー四面体分割を用いた局所構造に基づくタンパク質構造分類の考察

    第5回日本蛋白質科学会年会 

    Presentation date: 2005.06

  • 相同タンパク質の動的構造II.同一スーパーファミリー内での比較

    第5回日本蛋白質科学会年会 

    Presentation date: 2005.06

  • 相同タンパク質の動的構造I.ヒトリゾチームの動的構造に対するアミノ酸置換の影響

    第5回日本蛋白質科学会年会 

    Presentation date: 2005.06

  • Reflection of knowledge information in ProMode (a database of normal mode analyses on proteins)

    GIW2004 

    Presentation date: 2004.12

  • 完全グラフを利用したタンパク質のrigid domainの同定とSCOPへの応用

    日本生物物理学会第42回年会 

    Presentation date: 2004.12

  • ProMode−知見情報の基準振動アニメーションへの反映

    日本生物物理学会第42回年会 

    Presentation date: 2004.12

  • 格子タンパク質におけるアミノ酸置換による熱力学量の変化

    日本生物物理学会第42回年会 

    Presentation date: 2004.12

  • アミノ酸置換に伴うタンパク質の動的構造の変化−ヒトリゾチーム変異体における基準振動解析−

    日本生物物理学会第42回年会 

    Presentation date: 2004.12

  • ドロネー四面体コードを用いたタンパク質構造分類

    日本生物物理学会第42回年会 

    Presentation date: 2004.12

  • ドロネー四面体分割を用いたタンパク質構造比較

    FIT2004 

    Presentation date: 2004.09

  • Development of Energy-Minimization and Molecular Simulation Algorithm Considering Solvation Effects in Dihedral Angles Space

    The 1st Pacific-Rim International Conference on Protein Science 

    Presentation date: 2004.04

  • A Statictical Mechanical Model for Protein Folding: A Study on Three-Dimensional Lattice Proteins

    The 1st Pacific-Rim International Conference on Protein Science 

    Presentation date: 2004.04

  • ProMode: a collection and comparison of normal mode analysis results of protein molecules

    The 1st Pacific-Rim International Conference on Protein Science 

    Presentation date: 2004.04

  • Improvements in ProMode (a database of normal mode analyses of proteins)

    GIW2003 

    Presentation date: 2003.12

  • 溶媒効果を取り込んだ蛋白質エネルギー極小化アルゴリズムの2面角系への拡張

    第26回溶液化学シンポジウム 

    Presentation date: 2003.10

  • タンパク質フォールディング過程における天然接触ペアと非天然接触ペアの出現頻度と役割

    日本生物物理学会第41回年会 

    Presentation date: 2003.09

  • 単体・複合体の立体構造変化の解析による分子認識機構解析

    日本生物物理学会第41回年会 

    Presentation date: 2003.09

  • 2面角系における溶媒効果を取り込んだ蛋白質エネルギー極小化アルゴリズムの開発

    日本生物物理学会第41回年会 

    Presentation date: 2003.09

  • ProModeの開発と動的ドメインの解析

    日本生物物理学会第41回年会 

    Presentation date: 2003.09

  • 島模型によるタンパク質の構造変化の統計力学

    第3回日本蛋白質科学会年会 

    Presentation date: 2003.06

  • データベースを利用したタンパク質の分子認識機構の解析

    第3回日本蛋白質科学会年会 

    Presentation date: 2003.06

  • ProMode: タンパク質の基準振動データベースの解析−動的ドメインの同定−

    第3回日本蛋白質科学会年会 

    Presentation date: 2003.06

  • ProMode: A database of normal mode analysis of proteins.

    GIW2002 

    Presentation date: 2002.12

  • データベースを利用したタンパク質の分子認識機構の解析

    日本生物物理学会第40回年会 

    Presentation date: 2002.11

  • タンパク質フォールディングの統計力学モデル

    日本生物物理学会第40回年会 

    Presentation date: 2002.11

  • 複数鎖からなるタンパク質の基準振動解析

    日本生物物理学会第40回年会 

    Presentation date: 2002.11

  • タンパク質の基準振動解析データベースProMode

    日本生物物理学会第40回年会 

    Presentation date: 2002.11

  • パッチ解析におけるパッチ構成アミノ酸の統計的分析

    日本生物物理学会第40回年会 

    Presentation date: 2002.11

  • 蛋白質立体構造データベースの国際的運営(wwPDB)と高度化:PDBj

    第2回日本蛋白質科学会年会 

    Presentation date: 2002.06

  • 蛋白質の分子認識に伴う構造変化データベースの構築と解析

    第2回日本蛋白質科学会年会 

    Presentation date: 2002.06

  • 3次元格子タンパク質のフォールディングのモンテカルロ・シミュレーションと統計力学モデル

    第2回日本蛋白質科学会年会 

    Presentation date: 2002.06

  • Promode:タンパク質の基準振動解析データベースの作成

    第2回日本蛋白質科学会年会 

    Presentation date: 2002.06

  • 3次元格子タンパク質の再生・変性転移における局所構造

    日本生物物理学会第39回年会 

    Presentation date: 2001.10

  • 自由な局所構造模型による3次元格子タンパク質の折れたたみ過程

    日本生物物理学会第39回年会 

    Presentation date: 2001.10

  • タンパク質の分子認識に伴う構造変化データベースの構築と解析

    日本生物物理学会第39回年会 

    Presentation date: 2001.10

  • PROSITEパターン近傍の局所構造の解析

    日本生物物理学会第39回年会 

    Presentation date: 2001.10

  • Geometrical analysis of protein structures

    4-th International Conferenece on Biological Physics 

    Presentation date: 2001.07

  • Rigid local structure motifs in proteins detected by the Delaunay tessellation method.

    4-th International Conferenece on Biological Physics 

    Presentation date: 2001.07

  • Exploration of the structural space of proteins by molecular dynamics directed initially to normal modes

    4-th International Conferenece on Biological Physics 

    Presentation date: 2001.07

  • 同じ生構造(三次元格子タンパク質)をもつ二つのアミノ酸配列の再生・変性転移のモンテカルロ・シミュレーション

    第1回日本蛋白質科学会年会 

    Presentation date: 2001.06

  • 基準振動で方向づけられた分子動力学によるタンパク質構造空間の探索

    第1回日本蛋白質科学会年会 

    Presentation date: 2001.06

  • PROSITEパターンを含むrigidな局所構造の同定

    第1回日本蛋白質科学会年会 

    Presentation date: 2001.06

  • 複数のDelaunay四面体からなる局所構造モチーフの探索法の開発

    「タンパク質高次構造に基づくゲノム情報科学」第1回公開ワークショップ 

    Presentation date: 2001.01

  • p53の疎水性側鎖がオリゴマー化ドメインの3次構造に及ぼす影響

    第37回ペプチド討論会 

    Presentation date: 2000.10

  • タンパク質の基準振動で方向づけられた分子動力学

    日本生物物理学会第38回年会 

    Presentation date: 2000.09

  • 3次元格子タンパク質の再生・変性転移のモンテカルロ・シミュレーションと自由な局所構造模型

    日本生物物理学会第38回年会 

    Presentation date: 2000.09

  • 立体構造モチーフの表現と探索

    日本生物物理学会第38回年会 

    Presentation date: 2000.09

  • Analysis of structural motifs in proteins

    BGRS 2000 

    Presentation date: 2000.08

  • 分子動力学によるタンパク質の基準振動間のエネルギー移動の解析

    蛋白合同年会・東京2000(第12回日本蛋白工学会年会) 

    Presentation date: 2000.06

  • 蛋白質立体構造モチーフ解析

    蛋白合同年会・東京2000(第12回日本蛋白工学会年会) 

    Presentation date: 2000.06

▼display all

Research Projects

  • Development of intra-molecule dynamic structure network analysis method to characterize protein dynamics

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2016.04
    -
    2019.03
     

    Wako Hiroshi, ENDO Shigeru, TSUCHIYA Yuko

     View Summary

    We have performed normal mode analysis for many proteins for understanding their dynamic structures. Using these results, we defined an intra-molecular dynamic protein structure network (dPSN) for characterizing them. We applied this method to various types of proteins such as enzymes, allosteric proteins, and oligomeric proteins and found that a centrality measure, betweenness, is the most effective property because it is well correlated with structural and functional characteristics of amino acid residues. Since the motions of the lowest-frequency normal modes are related to functional motions of a protein, we defined dPSN individually for such normal modes and revealed the significant features of their motions. For example, the residues with high betweenness were found in active sites of enzyme proteins, in an allosteric pathway between an active and effective sites, and on the inter-subunit interface of oligomeric proteins, implying effectiveness of this method

  • Normal mode analysis of proteins using an elastic network model in dihedral angle space

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2006
    -
    2008
     

    WAKO Hiroshi, ENDO Shigeru

  • Analyses of binding normal modes in protein complexes and registration to the database ProMode

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2005
    -
    2007
     

    ENDO Shigeru, WAKO Hiroshi

     View Summary

    When an internal coordinate as a dihedral angle is used as the degree of freedom of a molecule, a decrease of the number of variables is favorable to calculation of normal modes in the molecule. However the normal mode analysis for a system of multiple molecules was hardly carried out because the handling of the external degree of freedom is complicated. To analyze more protein complexes in PDB without exception preferably the program in a dihedral angle system that we have developed heretofore was upgraded.In the normal mode analysis of a complex the displacement of each atom relative to the center of mass of a molecule in the complex, called internal motion, is obtained by applying an Eckart condition just to the molecule. The external motion is the difference between the normal mode of the whole complex and the internal motion. We defined the translation-rotation component in the motion of the center of mass of the molecule as the average of the external motion of all the atoms within the molecule and then analyzed binding normal modes which have large translation-rotation component. In the analyzed dozens kinds of protease-inhibitor complexes and antigen-antibody ones the mode with a significant translational motion existed hardly and the rotational component is localized only to a few modes. It is suggested that the dynamic structure of the complex could be classified from the distribution of binding normal modes. The analyzed results was registered in ProMode (the database of normal mode analyses of proteins) and introduced to the public. Web pages that display the internal motion, the external motion, and those correlation for each molecule was added to the database server

  • A comparative study of dynamic structures of proteins by using normal mode analysis database.

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2003
    -
    2005
     

    WAKO Hiroshi, ENDO Shigeru

     View Summary

    In this study we considered that a comparative study of normal mode analysis for wild-type and mutant lysozymes and for several proteins in the same superfamily could provide some valuable information about dynamic structures of proteins.1.In the study of lysozymes it was found that the changes in the dynamic structures (defined as changes in fluctuations of the amino acid residues here) of the mutant lysozymes from the wild-type one had little correlation with those in the static structures. In order to reveal the basic changes caused by amino acid substitutions we performed a principal component analysis of the fluctuations of amino acid residues with the various mutant lysozymes. As a result, it was found that the domain motions are essential to the fluctuations of the individual amino acid residues. Furthermore, it was found that the correlative movements of the specific atom pairs in the active site should be maintained for the activity of the mutant lysozymes.2.In the comparative study of homologous proteins, the proteins were structurally aligned and then the fluctuations of the amino acids were compared at the equivalent sites. Although their amino acid sequences considerably differed in some cases (but their folds were very similar), the fluctuations of the amino acid residues at the equivalent sites in the secondary structure regions agreed well not only qualitatively but also quantitatively with each other. On the other hand, in the loop regions, since the fluctuations were essentially larger and affected by the insertion and deletion of amino acid residues, the changes in the fluctuations differed quantitatively. Furthermore, the dynamic domains were compared. The common regions constructing the dynamic domains among the homologous proteins were detected by visually inspecting their structures best-fitted. Such regions are considered to form a nucleus in the dynamic structure of the superfamily. This kind of observation can be obtained only when several proteins derived from the database we constructed are compared

  • Classification and analysis of local structure motifs in protein conformations

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    1999
    -
    2001
     

    WAKO Hiroshi

     View Summary

    In order to reveal a principal of protein architectures we identified local structure motifs commonly found in different protein conformations and analyzed them. For this purpose we used the method developed by ourselves, in which Delaunay tessellation is applied to protein conformations and codes are assigned to Delaunay tetrahedrons to characterize the local structures containing them. In this research we carried out the following.(1) The rules to assign the Delaunay codes were modified so that they could represent characteristics of the local structures more properly and be applied to the proteins constructed with more than one chain.(2) A new algorithm was developed to detect a local structural motif consisting of more than one tetrahedron.(3) Application 1 : We prepared to construct local-structure database.(4) Application 2 : Making use of the local-structure codes site-dependent and environment-dependent frequencies of amino acid occurrences were examined for α-helix.(5) Application 3 : We defined a hydrophobic core as the local structure containing a Delaunay tetrahedron with four vertices occupies by the hydrophobic amino acid residues. Then such structures were studied.(6) Application 4 : Using local structure codes, the method was developed to classify proteins with the same amino acid sequence motif with each other in more detail.(7) Application 5 : Using the algorithm described in (2) we analyzed the characteristics of the relatively larger local structures observed in homologous or non-homologous proteins

  • The dynamic structure of protein molecules based on coupling among normal modes

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    1999
    -
    2000
     

    ENDO Shigeru, WAKO Hiroshi

     View Summary

    This research aims to investigate complicated motions of a protein systematically by the molecular dynamics with the initial velocity in the direction of each normal mode of a protein molecule from the viewpoint that linear movement of normal modes is extended to the nonlinear range. In normal mode analyses, since the number of variables describing the three-dimensional structure of a molecule decreased, internal coordinates like dihedral angles were often used. The dihedral angle coordinate system was also used for the program of molecular dynamics (FEDER/3) which we have developed.Molecular dynamics were performed in all the directions along about 300 normal modes lower than 200cm^<-1>, respectively for 434Cro and 434 repressor, and P22c2 repressor, which are homologous proteins. When the temperature per each mode was 300K (about 0.7 K for the whole molecule), the movement initialized with a mode faster than 40cm^<-1> resulted in harmonic oscillation with the fiequency expected from the mode. In higher temperature it was observed that the energy in a mode was dissipated to other modes, in which the energy had a tendency to move to modes roughly corresponding to the second harmonic. In the dynamics initialized with a mode slower than 40cm^<-1>, it was observed also in 300K that the tertiary structure was transferred to that around an energy minimum other than the energy minimum where the normal mode analysis was done. Energy minimization from low-energy states in the trajectories, which started from several different normal modes, however converged to the same energy minimum. That is, the number of energy minima near the native structure was not so many, for example of 434Cro, ones which were able to be transferred at 300K and at 1500K were seven and 32, respectively. It was proved that using this protocol the energy minima near the native structure can be systematically explored even in complicated multidimensional structural space of a protein

  • Evolution of Gonadotropic Hormones : Molecular and Morphological Approaches

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    1998
    -
    2000
     

    ISHII Susumu, WAKO Hiroshi, KAWASAKI Daisuke, ARAI Yuta, KIKUYAMA Sakae, ISHIGAKI Haruo

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    A.Evolution of pituitary glycoprotein hormone alpha subunit in vertebrates1) cDNAs encoding the alpha subunits of lungfishes, elasmobranchs, an acipenser, amphibians and reptiles were cloned and the primary structures of the subunit molecules were deduced.2) By comparing the molecular structures, we supposed that the evolution speed of the alpha subunit was extremely faster in actinopterygian fishes than in the other vertebrate lineages. We also found a fact indicating that the evlolution speed of the alpha subunit molecule was faster in the anamnian lineage than in the amniote linage.B.Evolution of gonadotropin beta subunits in vertebrates1) We also cloned cDNAs for the gonadotropin beta subunits in a lungfish, amphibians and reptilians, and the primary structure of these molecules were deduced..2) We found that the luteinizing hormone (LH) beta subunits were more diversified than the follicle-stimulating hormone (FSH) beta subunits in vertebrates. The evolution speed of the LH beta subunit was supposed to be faster in amuniotes than in anamunians.C.Our study strongly suggests that the gonadotropin subunit molecules have evolved with different speeds among the hormone or subunit species and also among the animal groups in vertebrates. Pituitary structure also shows similar variations as in the molecules

  • Administration of researches on principles of protein architecture

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    1995
    -
    1999
     

    GO Nobuhiro, KUWAJIMA Kunihiro, WAKO Hiroshi, YUTANI Katsuhide, KITAO Akio, KIDERA Akinori

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    The research project, "Principle of Protein Architecture," has continued its activity during FY1995-1998 for the purpose of pursuing an evolutional and/or physicochemical solution to the question "how the information of protein's three dimensional structure and function is coded in its amino acid sequence."When starting this project, we had relied on the hypothesis that the variety of protein folds is limited to a rather small number, about one thousand. Based on such a hypothesis, we imagined a realization of the prediction of protein structures using the 'threading' method. The results of the research done for the four years show adual and significant improvements in terms of the practical goal of prediction, but with no clear-cut success, indicating the essentially complex nature of the problem.Together with organizing such forefront research efforts, we contributed significantly to the activation of the related fleldsin Japan. To the open workshop we organized annually, more than 400 participants and more than 200 poster presentations were contributed.In FY1999, we carried out of activities of organizing the research results made during the four years and disseminating them widely to academic and more general public. In particular we (1) prepared publication of a monograph covering the research results, and (2) organized an open workshop. (1) We have carried out planning of publication of the research results as a special volume of "Protein, Enzyme and Nucleic Acid," which is one of the most important review journal in Japan. We had editorial meetings twice in order to discuss the basic concept of the planned volume. We will soon propose the publication to the publisher. (2) At first we organized an open workshop, which is a continuation of a series of symposia we have had organized annually during the tenure of the Grant-in-Aid Scientific Research, also this year on June 14 at Kanagawa Prefectural Hall. The workshop was very active, having more than 350 participants

  • Protein structure, comparison, prediction, and design

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    1995
    -
    1999
     

    GO Nobuhiro, YURA Kei, NISHIKAWA Ken, WAKO Hiroshi, YOMO Tetsuya, ISHIMORI Koichiro

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    Natural history group (Go, Yura, Wako, Nishikawa, Mitaku, and Umeyama)From a classification of the spatial arrangements of the secondary structure elements, Go discovered 'the symmetry rule', whish states that apair of similar protein folds, having no common ancestor, tend to possessan internal symmetry in their fold. Yura found two types of 'modules', a phosphate binding module observed commonly in polymerases and transcription factors, and a substrate-specificity determining module of peroxidases. A newly developed method for detecting similarity in the atomic level revealed a lot of similar ATP binding structures in totally different folds (Go). Wako developed an efficient algorithm of expressing the local environment by a code representation. A new secondary structure prediction method was developed by Nishikawa, who applied the threading method for this purpose. As for the structural prediction for membrane bound proteins, Mitaku improved his method to predict the structure of bacteriorhodopsin correctly. Umeyama established a fully automated algorithm of homology modeling, which is estimated to give a sufficient accuracy.Design group (Yomo and Ishimori)Yomo found in random mutagenesis experiments on catalase that the thermal stability and activity of the protein is extremely robust against mutations, and that a possibility of the functional optimization by the evolutional engineering technique can enormously enhanced by the elongation of the chain length. The concept of 'module' was applied to produce chimera hemoglobin, which was synthesized by exchanging its modules each other. From such chimera proteins, Ishimori confirmed that the structural unit, module, works not only as the unit of maintaining the protein stability, but also as a unit for realizing the function of hemoglobin

  • Evolution of pituitary hormones

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    1992
    -
    1995
     

    ISHII Susumu, ISHIGAKI Haruo, KUBOKAWA Kaoru, KIKUCHI Motoshi, WAKO Hiroshi, KIKUYAMA Sakae

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    We have cloned cDNAs encoding precursor molecules of luteinizing hormone (LH) beta subunits of the chicken and Japanese quail, the beta subunit of follicle-stimulating hormone of Japanese quail and alpha subunits of the Japanese quail, bullfrog, toad and Australian lung-fish. Using these data and data of other vertebrate species reported, we compared the primary structure of the molecules among vertebrate species. The primary structure of the alpha subunits was highly conserved and that of the beta subunits was less conserved. We also predicted the secondary sturctures of the alpha and beta subunits of these gonadotropins and thyrotropins. It was very well coincided among vertebrate species in both subunits. We concluded that the three dimensional structure is more highly conserved than the primary structure in vertebrates. We constructed a phylogenic tree of the beta subunits of gonadotropins and thyrotropin. It was found that follicle-stimulating hormone is more closely related to thyrotropin than luteinizing hormone. This is different from the classic grouping of members of the gonadotropin/thyrotropin family in which follicle-stimulating hormone and luteinizing hormone used to be categorized together as gonadotropin and thyrotropin was separated from gonadotropin. We also found that the alpha subunit of Australian lung-fish is more closely related to alpha subunits of tetrapod vertebrates than to those of teleosts. A similar result was obtained in neurohypophyseal hormone precursor molecules

  • 蛋白質の高次構造研究のためのユーティリティ・プログラムの開発

    日本学術振興会  科学研究費助成事業

    Project Year :

    1987
     
     
     

    輪湖 博

  • アミノ酸残基間の空間的距離の情報から蛋白質の立体構造を推測する方法の開発

    日本学術振興会  科学研究費助成事業

    Project Year :

    1986
     
     
     

    輪湖 博

  • 立体構造エネルギー解析法による蛋白質の三次構造に関する研究

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    蛋白質分子の立体構造エネルギー解析法とよばれるものには、立体構造エネルギー極小化,規準振動解析,モンテ・カルロ法,分子動力学等があるが、これらを統合した、総合的な蛋白質解析システムを構築することをめざして研究を進めている。このうち、エネルギー極小化に関してはほぼ完成の域に達しているので、本年度は、規準振動解析を集中的に行なった。1.蛋白質に関する実験結果を理解する上で、X線結晶構造解析で得られた立体構造を観察することが重要な役割を担っていることは明らかである。この「静的描像に対し、規準振動解析は「動的描像を付加することができる。確かに、モンテ・カルロ法や分子動力学に比べ適用範囲の限界が狭い難点はあるが、一方で、計算が手軽であるという十分意義のある長所がある。リボヌクレアーゼ,フラボドキシンなどいくつかの蛋白質について、各原子の常温でのゆらぎ,原子対のゆらぎの相関,二面角のゆらぎ等を計算し、蛋白質それぞれの立体構造の特徴(折れたたみのタイプ,ドメイン構造,モジュール構造,二次構造等)がどのように反映するかを調べた。その結果、規準振動解析の有効性を確認することができた。2.蛋白質分子のような複雑な系のしくみを解明するための方法論というものは必ずしも確立されているとは言えないが、天然構造に外から何らかの摂動を加え、その応答を調べるのは一つの方法であろう。本年度は、その発想のもとに、BPTIという蛋白質について、天然構造で形成されている3本のS-S結合のうち1本、2本あるいは3本を切断した場合、分子内のゆらぎがどう変化するかを計算することによって、天然構造における3本のS-S結合の役割を調べた。その結果、立体構造を保持するのに重要と思われるものと、むしろ、折れたたみの過程において重要であろうと思われるものとがあることが明らかになった

  • タンパク質の立体構造の計算機による解析法の開発とそれを用いた立体構造の解析

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    1.タンパク質の立体構造解析プログラムFEDER/2の開発(1)タンパク質のみを対象としたプログラムFEDERを、ツリ-構造をもつ分子一般に拡張するため、アルゴリズムとデ-タ構造の改良を行った。(2)真空中だけでなく、水溶液中のシミュレ-ションも行うことができるようにするため、水和殻モデルによる水和エネルギ-の計算機能を追加した。(3)値の大きな極小植からの回避は極小化法の重要な機能の一つであるが、可変目的関数法、シミュレ-ティド・アニ-リング法、モンテカルロ法、linearized embedding法などの手法を適用できるよう改良した。(4)複数鎖からなる系を取り扱うことができるように、現在プログラムを改良中である。2.タンパク質の立体構造の解析(1)基準振動解析によって、動的視点から、タンパク質のドメイン構造を研究した。(2)真空中と水和エネルギ-を考慮した系でシミュレ-ションを行い、その比較研究を行った。(3)オキシトシンの溶液中のNMR距離解析デ-タをもとに立体構造決定の問題を取り扱い、その構造の多形性について研究を行った。(4)立体構造既知のタンパク質から統計的解析によって得られた経験的な距離情報が、アミノ酸配列だけから高次構造を推定しようとするときどれだけの情報量をもつか研究した。(5)極小化法を改良するために、BPTIのX線結晶構造をもとにNMR距離解析の擬似デ-タを作成し、初期値の問題、立体構造エネルギ-の問題などを研究した

  • ゲノム情報からのタンパク質構造の分類と予測

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    ゲノムにコードされた全タンパク質を対象に、立体構造予測をはじめとする既存の配列データ解析ツールを動員した自動解析を行い、その結果をGTOPデータベースとして公開している。実験的に解明されるゲノム配列の増大にともない、GTOPに収録された生物種は昨年の70種から101種へと拡大した。なかでも真核生物では新たに分裂酵母、フグ、マウス(cDNA)を追加した。なお、これら以外に27種のファージも加えた。GTOPの応用研究としては、昨年行った大腸菌ゲノム中の偽遺伝子の同定に関する研究に続き、本年度は主に多細胞真核生物に的を絞り、選択的スプライシングによって生成されるタンパク質は立体構造的にみてどのような影響を受けるか、という問題意識のもとにデータ解析を行った。この研究では元データとなる完全長cDNA配列の信頼性に問題がある(実験エラーの可能性)ため解析が進めにくく、信頼が置けると思われる配列データのみに絞り込み、解析結果をまとめてつつある。第2のテーマとして、GTOPの構造予測結果をもとに、全ゲノム配列が決定されている生物種を対象に、ドメインの組合せパターンを網羅的に調べた。その中で特に原核生物が持つドメインの組合せパターンに着目して生物種間の比較を行った結果、エキソン・シャッフリングを起こし得ない原核生物の構造遺伝子でも進化の過程でドメインの組合せパターンが変化した例がいくつか見出された。第3のテーマとして、タンパク質の局所構造の性格をダイナミクスの観点から明らかにするために、基準振動解析を利用した研究を行った。具体的には、各基準振動モードについて、各原子ペアのゆらぎベクトルの内積をとり、正の相関が強い原子がそれぞれ一つの集合を構成するようクラスター化する方法を開発し、解析を行った。これによって、ダイナミクスの観点からタンパク質ドメインを定義することを可能とした

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Internal Special Research Projects

  • 基準振動解析によるタンパク質ダイナミクスの比較研究

    2002  

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     タンパク質立体構造の構築原理を明らかにし、構造と機能の関係を理解することは、構造生物学、バイオインフォーマティクスなどにおけるポスト・ゲノムの重要な研究課題の一つである。そこでは、静的構造のみならず、動的構造を考慮した研究が不可欠であることが広く認識されているものの、ダイナミクスに関する研究の多くは個別のタンパク質に関するもので、より多くのタンパク質のダイナミクスを比較研究することによって、より大局的な視点から解析したものは殆んどないのが現状である。そこで本研究では、われわれが現在構築中のタンパク質の基準振動解析データベースを利用して、多くのタンパク質の動的構造を比較し、立体構造の構築原理、そして構造・機能相関の問題にアプローチすることを目的として研究を行ってきた。 本年度は、まず、より多くのタンパク質について基準振動解析を行い、そのデータを蓄積した。 その上で、タンパク質の立体構造を構成する部品としての局所構造の性格をダイナミクスの観点から明らかにするために、各基準振動モードについて、各原子ペアのゆらぎベクトルの内積をとり、正の相関が強い原子がそれぞれ一つの集合を構成するようクラスター化することによってドメインを定義する方法を開発した。これまで、動的なドメインを定義する方法にはDynDomというソフトがよく使われているが、この方法では、見た目あきらかにドメインが存在すると思われる場合でも定義されない場合が多く、その後の解析ができないという欠点があった。本研究で開発した方法はそれを補うことができ、ダイナミクスの観点からドメインを定義し、タンパク質立体構造の構築原理を考える上で、新たな視点を提供することができると思う。今後、得られたドメインを分類し、性格付けしていく予定である。

  • 二面角空間でのタンパク質の分子動力学シミュレーション

    1997  

     View Summary

    タンパク質の立体構造をその立体構造エネルギーという観点から解析し、研究するために、これまで、エネルギーの最小化、基準振動解析、モンテカルロ・シミュレーションを二面角を変数として実行するプログラムFEDERの開発を行ってきた。しかし、二面角を変数とする分子動力学計算に関しては、変数の3乗に比例する計算量が必要と考えられ、実用的でなかったため、プログラムの開発を見送ってきた経緯がある。しかし、近年、変数の1乗に比例する計算量で可能なアルゴリズムが相次いで発表されたことを受けて、われわれのプログラムFEDERにもその機能を付加し、分子動力学シミュレーションを行ってみることとした。 結果的に2つのアルゴリズムを試すこととなった。最初に採用したJainらのアルゴリズムは、シミュレーションを続けるうちに運動量が変動し、計算が不安定になる欠点があることがわかった。そこで新たにMazurらのアルゴリズムを採用したプログラムを開発した。こちらは、運動量保存がアルゴリズム的に保証されており、現在までに行ったテストの結果では、少なくとも通常の環境設定でのシミュレーションはJainらのものより安定に進行することがわかった。しかし、非常にエネルギーが高い初期値、非常な高温、非常に大きな系でのシミュレーションにはついてはまだ十分に検討しておらず、改良が必要となる可能性もある。また、並行して、最小エネルギー構造のまわりでの基準振動モードにそったゆらぎのシミュレーションについてもテスト計算を行った。 今後、プログラムの改良とともに、具体的なタンパク質を設定してシミュレーションを行う予定である。