Analysis on the structural polymorphism of IDPs by computer simulation

2013 Fiscal Year Final Research Report

• Project Area: Target recognition and expression mechanism of intrinsically disordered protein
• Project/Area Number: 21113006
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: HIGO Junichi 大阪大学, たんぱく質研究所, 特任研究員 (80265719)
• Co-Investigator(Kenkyū-buntansha): TAKANO Mitsunori 早稲田大学, 理工学術院, 教授 (40313168) ; KIKUCHI Macoto 大阪大学, サイバーメディアセンター, 教授 (50195210)
• Project Period (FY): 2009-07-23 – 2014-03-31
• Keywords: フォールディング / ドッキング / 自由エネルギー地形

Research Abstract

Computer simulations were performed to physico-chemically understand the coupled folding and binding of intrinsically disordered proteins (IDPs). We expressed the system (IDP, its partner molecule, and solvent molecules) by an all-atom model, and an effective conformational sampling method, multicanonical molecular dynamics, was applied to the system. We visualized the fine structure of a free-energy landscape of the coupled folding and binding of the system. The free-energy landscape consisted of the native-like complex cluster and small non-native complex clusters, where free-energy barriers separated the clusters. Then, to understand the precise free-energy landscape from a more physical point of view, we used a coarse-grained model. The inter-cluster conformational transitions were explained by cooperative and competitive interactions in IDPs.

Research Products

• [Journal Article] Coupling of Lever Arm Swing and Biased Brownian Motion in Actomyosin (2014)
  • Author(s): Nie, QM., Togashi, A., Sasaki, TN., Takano, M., Sasai, M., Terada, TP
  • Journal Title: PLoS Comput Biol Volume: 10 Pages: e1003552
  • DOI: 10.1371/journal.pcbi.1003552
  • Peer Reviewed
• [Journal Article] A virtual-system coupled multicanonical molecular dynamics simulation : Principle and its application to free-energy landscape of protein-protein interaction with an all-atom model in explicit solvent (2013)
  • Author(s): Higo, J., Umezawa, K., Nakamura, H
  • Journal Title: J. Chem. Phys Volume: 138 Pages: 184106
  • DOI: 10.1063/1.4803468
  • Peer Reviewed
• [Journal Article] Structural flexibility of intrinsically disordered proteins induces stepwise target recognition (2013)
  • Author(s): Shirai, N.C., Kikuchi, M
  • Journal Title: J. Chem. Phys Volume: 139 Pages: 225103
  • DOI: 10.1063/1.4838476
  • Peer Reviewed
• [Journal Article] Frustration-induced protein intrinsic disorder (2013)
  • Author(s): Matsushita, K., Kikuchi, M
  • Journal Title: J. Chem. Phys Volume: 138 Pages: 105101
  • DOI: 10.1063/1.4794781
  • Peer Reviewed
• [Journal Article] Virtual states introduced for overcoming entropic barriers in conformational space (2012)
  • Author(s): Higo, J., Nakamura, H
  • Journal Title: Biophysics Volume: 8 Pages: 139-144
  • DOI: 10.2142/biophysics.8.139
  • Peer Reviewed
• [Journal Article] Enhanced and effective conformational sampling of protein molecular systems for their free energy landscapes (2012)
  • Author(s): Higo, J., Ikebe, J., Kamiya, N., Nakamura, H
  • Journal Title: Biophysical Rev Volume: 4 Pages: 27-44
  • DOI: 10.1007/s12551-011-0063-6
• [Journal Article] Conformational Ensembles of an Intrinsically Disordered Protein pKID with and without a KIX Domain in Explicit Solvent Investigated by All-Atom Multicanonical Molecular Dynamics (2012)
  • Author(s): Umezawa, K., Ikebe, J., Takano, M., Nakamura, H., Higo, J
  • Journal Title: Biomolecules Volume: 2 Pages: 104-121
  • DOI: 10.3390/biom2010104
  • Peer Reviewed
• [Journal Article] A Free-energy Landscape for Coupled Folding and Binding of an Intrinsically Disordered Protein in Explicit Solvent from Detailed All-atom Computations (2011)
  • Author(s): Higo, J., Nishimura, Y., Nakamura, H
  • Journal Title: J. Am. Chem. Soc Volume: 133 Pages: 10448-10458
  • DOI: 10.1021/ja110338e
  • Peer Reviewed
• [Journal Article] Theory for Trivial Trajectory Parallelization of Multicanonical Molecular Dynamics and Application to a Polypeptide in Water (2011)
  • Author(s): Ikebe, J., Umezawa, K., Kamiya, N., Sugihara, T., Yonezawa, Y., Takano, Y., Nakamura, H., Higo, J
  • Journal Title: J. Comput. Chem. Volume: 32 Pages: 1286-1297
  • DOI: 10.1002/jcc.21710
  • Peer Reviewed
• [Journal Article] Unidirectional Brownian motion observed in an in silico single molecule experiment of an actomyosin motor (2010)
  • Author(s): Takano, M., Terada, T.P., Sasai, M
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Pages: 7769-7774
  • DOI: 10.1073/pnas.0911830107
  • Peer Reviewed
• [Journal Article] Residue network in protein native structure belongs to the universality class of a three-dimensional critical percolation cluster (2009)
  • Author(s): Morita, H., Takano, M
  • Journal Title: Phys. Rev Volume: E 79 Pages: 020901®
  • DOI: 10.1103/PhysRevE.79.020901
  • Peer Reviewed
• [Book] Free-energy landscape of Intrinsically disordered proteins investigated by all-atom multicanonical molecular dynamics, Chapter 14 in "Protein Conformational Dynamics" (Han, K., Zhang, X., and Yang, M.eds.) Advances in Experimental Medicine and Biology 805 (2014)
  • Author(s): Higo, J., Umezawa, K
  • Total Pages: 331-351
  • Publisher: Springer
• [Remarks]
  • URL: http://www.tsurumi.yokohama-cu.ac.jp/IDP/