title: Parallel Cascade Selection Molecular Dynamics (PaCS-MD) to generate conformational transition pathway.
abstract: Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is proposed as a molecular simulation method to generate conformational transition pathway under the condition that a set of "reactant" and "product" structures is known a priori. In PaCS-MD, the cycle of short multiple independent molecular dynamics simulations and selection of the structures close to the product structure for the next cycle are repeated until the simulated structures move sufficiently close to the product. Folding of 10-residue mini-protein chignolin from the extended to native structures and open-close conformational transition of T4 lysozyme were investigated by PaCS-MD. In both cases, tens of cycles of 100-ps MD were sufficient to reach the product structures, indicating the efficient generation of conformational transition pathway in PaCS-MD with a series of conventional MD without additional external biases. Using the snapshots along the pathway as the initial coordinates, free energy landscapes were calculated by the combination with multiple independent umbrella samplings to statistically elucidate the conformational transition pathways.
authors.affiliation: Department of Physics, Graduate School of Science, The University of Tokyo, Tokyo, 7-3-1, Hongo, Japan.
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Harada
authors.forename: Akio
authors.initials: A
authors.lastname: Kitao
mesh_terms: D017122:Bacteriophage T4 / Q000201:enzymology; D056004:Molecular Dynamics Simulation; D009113:Muramidase / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D009842:Oligopeptides; D012997:Solvents; C506175:chignolin; D009113:Muramidase