Multiscale molecular dynamics simulations of rotary motor proteins
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Protein functions require specific structures frequently coupled with conformational changes. The scale of the structural dynamics of proteins spans from the atomic to the molecular level. Theoretically, all-atom molecular dynamics (MD) simulation is a powerful tool to investigate protein dynamics because the MD simulation is capable of capturing conformational changes obeying the intrinsically structural features. However, to study long-timescale dynamics, efficient sampling techniques and coarse-grained (CG) approaches coupled with all-atom MD simulations, termed multiscale MD simulations, are required to overcome the timescale limitation in all-atom MD simulations. Here, we review two examples of rotary motor proteins examined using free energy landscape (FEL) analysis and CG-MD simulations. In the FEL analysis, FEL is calculated as a function of reaction coordinates, and the long-timescale dynamics corresponding to conformational changes is described as transitions on the FEL surface. Another approach is the utilization of the CG model, in which the CG parameters are tuned using the fluctuation matching methodology with all-atom MD simulations. The long-timespan dynamics is then elucidated straightforwardly by using CG-MD simulations.
KeywordsMolecular dynamics simulation Free energy calculation Coarse-grained molecular dynamics simulation F1-ATPase V1-ATPase
This work was financially supported by Innovative Drug Discovery Infrastructure through Functional Control of Biomolecular Systems, Priority Issue 1 in Post-K Supercomputer Development from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to M.I. (Project ID: hp150269, hp160223, and hp170255); by Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS) from Japan Agency for Medical Research and Development (AMED) to M.I.; and by RIKEN Dynamic Structural Biology Project to M.I. We further thank collaborators Dr. Yuko Ito (AIST), Dr. Tomotaka Oroguchi (Keio University), Dr. Takashi Yoshidome (Tohoku University), Prof. Nobuyuki Matubayasi (Osaka Univeristy), Prof. Masahiro Kinoshita (Kyoto University), Dr. Yuta Isaka (FBRI), Dr. Yuichi Kokabu (MKI), Prof. Ichiro Yamato (Tokyo University of Science), and Prof. Takeshi Murata (Chiba University).
Compliance with ethical standards
Conflicts of interest
T. Ekimoto declares that he has no conflict of interest. M. Ikeguchi declare that he has no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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