title: FF12MC: A revised AMBER forcefield and new protein simulation protocol.
abstract: Specialized to simulate proteins in molecular dynamics (MD) simulations with explicit solvation, FF12MC is a combination of a new protein simulation protocol employing uniformly reduced atomic masses by tenfold and a revised AMBER forcefield FF99 with (i) shortened CH bonds, (ii) removal of torsions involving a nonperipheral sp(3) atom, and (iii) reduced 1-4 interaction scaling factors of torsions ϕ and ψ. This article reports that in multiple, distinct, independent, unrestricted, unbiased, isobaric-isothermal, and classical MD simulations FF12MC can (i) simulate the experimentally observed flipping between left- and right-handed configurations for C14-C38 of BPTI in solution, (ii) autonomously fold chignolin, CLN025, and Trp-cage with folding times that agree with the experimental values, (iii) simulate subsequent unfolding and refolding of these miniproteins, and (iv) achieve a robust Z score of 1.33 for refining protein models TMR01, TMR04, and TMR07. By comparison, the latest general-purpose AMBER forcefield FF14SB locks the C14-C38 bond to the right-handed configuration in solution under the same protein simulation conditions. Statistical survival analysis shows that FF12MC folds chignolin and CLN025 in isobaric-isothermal MD simulations 2-4 times faster than FF14SB under the same protein simulation conditions. These results suggest that FF12MC may be used for protein simulations to study kinetics and thermodynamics of miniprotein folding as well as protein structure and dynamics. Proteins 2016; 84:1490-1516. © 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.
authors.affiliation: Computer-Aided Molecular Design Laboratory, Mayo Clinic, Rochester, MN, 55905, USA. pang@mayo.edu.
authors.forename: Yuan-Ping
authors.initials: YP
authors.lastname: Pang
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry; D007611:Aprotinin / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009113:Muramidase / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017510:Protein Folding; D058849:Protein Refolding; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D013816:Thermodynamics; D025801:Ubiquitin / Q000737:chemistry
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; C472766:Gb3 antigen; D009842:Oligopeptides; D010455:Peptides; C508725:Trp-cage peptide; D025801:Ubiquitin; C549508:YYDPETGTWY; C506175:chignolin; D007611:Aprotinin; D009113:Muramidase
keywords: BPTI; CLN025; Trp-cage; chignolin; force field; molecular dynamics simulation; protein dynamics; protein folding; protein simulation; protein structure refinement