title: Domain Motion Enhanced (DoME) Model for Efficient Conformational Sampling of Multidomain Proteins.
abstract: Large conformational changes of multidomain proteins are difficult to simulate using all-atom molecular dynamics (MD) due to the slow time scale. We show that a simple modification of the structure-based coarse-grained (CG) model enables a stable and efficient MD simulation of those proteins. "Motion Tree", a tree diagram that describes conformational changes between two structures in a protein, provides information on rigid structural units (domains) and the magnitudes of domain motions. In our new CG model, which we call the DoME (domain motion enhanced) model, interdomain interactions are defined as being inversely proportional to the magnitude of the domain motions in the diagram, whereas intradomain interactions are kept constant. We applied the DoME model in combination with the Go model to simulations of adenylate kinase (AdK). The results of the DoME-Go simulation are consistent with an all-atom MD simulation for 10 μs as well as known experimental data. Unlike the conventional Go model, the DoME-Go model yields stable simulation trajectories against temperature changes and conformational transitions are easily sampled despite domain rigidity. Evidently, identification of domains and their interfaces is useful approach for CG modeling of multidomain proteins.
authors.affiliation: RIKEN Advanced Institute for Computational Science, 6-7-1 minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 640-0047, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Kobayashi
authors.affiliation: RIKEN Advanced Institute for Computational Science, 6-7-1 minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 640-0047, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsunaga
authors.affiliation: Graduate School of Information Science, Nagoya University , Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Koike
authors.affiliation: Graduate School of Information Science, Nagoya University , Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan.
authors.forename: Motonori
authors.initials: M
authors.lastname: Ota
authors.affiliation: RIKEN Advanced Institute for Computational Science, 6-7-1 minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 640-0047, Japan.|RIKEN Quantitative Biology Center, 7-1-26 minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 640-0047, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sugita
mesh_terms: D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins