title: Modeling Structural Dynamics of Biomolecular Complexes by Coarse-Grained Molecular Simulations.
abstract: Due to hierarchic nature of biomolecular systems, their computational modeling calls for multiscale approaches, in which coarse-grained (CG) simulations are used to address long-time dynamics of large systems. Here, we review recent developments and applications of CG modeling methods, focusing on our methods primarily for proteins, DNA, and their complexes. These methods have been implemented in the CG biomolecular simulator, CafeMol. Our CG model has resolution such that ∼10 non-hydrogen atoms are grouped into one CG particle on average. For proteins, each amino acid is represented by one CG particle. For DNA, one nucleotide is simplified by three CG particles, representing sugar, phosphate, and base. The protein modeling is based on the idea that proteins have a globally funnel-like energy landscape, which is encoded in the structure-based potential energy function. We first describe two representative minimal models of proteins, called the elastic network model and the classic Go̅ model. We then present a more elaborate protein model, which extends the minimal model to incorporate sequence and context dependent local flexibility and nonlocal contacts. For DNA, we describe a model developed by de Pablo's group that was tuned to well reproduce sequence-dependent structural and thermodynamic experimental data for single- and double-stranded DNAs. Protein-DNA interactions are modeled either by the structure-based term for specific cases or by electrostatic and excluded volume terms for nonspecific cases. We also discuss the time scale mapping in CG molecular dynamics simulations. While the apparent single time step of our CGMD is about 10 times larger than that in the fully atomistic molecular dynamics for small-scale dynamics, large-scale motions can be further accelerated by two-orders of magnitude with the use of CG model and a low friction constant in Langevin dynamics. Next, we present four examples of applications. First, the classic Go̅ model was used to emulate one ATP cycle of a molecular motor, kinesin. Second, nonspecific protein-DNA binding was studied by a combination of elaborate protein and DNA models. Third, a transcription factor, p53, that contains highly fluctuating regions was simulated on two perpendicularly arranged DNA segments, addressing intersegmental transfer of p53. Fourth, we simulated structural dynamics of dinucleosomes connected by a linker DNA finding distinct types of internucleosome docking and salt-concentration-dependent compaction. Finally, we discuss many of limitations in the current approaches and future directions. Especially, more accurate electrostatic treatment and a phospholipid model that matches our CG resolutions are of immediate importance.
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University , Sakyo, Kyoto 6068502, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Takada
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University , Sakyo, Kyoto 6068502, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kanada
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University , Sakyo, Kyoto 6068502, Japan.
authors.forename: Cheng
authors.initials: C
authors.lastname: Tan
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University , 650 W 168 Street New York, New York 10032, United States.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Terakawa
authors.affiliation: Department of Physics, Nanjing University , Nanjing 210093, China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Li
authors.affiliation: Advanced Center for Computing and Communication, RIKEN , Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Kenzaki
mesh_terms: D004247:DNA / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins; D004247:DNA