title: Residue-specific force field based on the protein coil library. RSFF1: modification of OPLS-AA/L.
abstract: Traditional protein force fields use one set of parameters for most of the 20 amino acids (AAs), allowing transferability of the parameters. However, a significant shortcoming is the difficulty to fit the Ramachandran plots of all AA residues simultaneously, affecting the accuracy of the force field. In this Feature Article, we report a new strategy for protein force field parametrization. Backbone and side-chain conformational distributions of all 20 AA residues obtained from protein coil library were used as the target data. The dihedral angle (torsion) potentials and some local nonbonded (1-4/1-5/1-6) interactions in OPLS-AA/L force field were modified such that the target data can be excellently reproduced by molecular dynamics simulations of dipeptides (blocked AAs) in explicit water, resulting in a new force field with AA-specific parameters, RSFF1. An efficient free energy decomposition approach was developed to separate the corrections on ϕ and ψ from the two-dimensional Ramachandran plots. RSFF1 is shown to reproduce the experimental NMR (3)J-coupling constants of AA dipeptides better than other force fields. It has a good balance between α-helical and β-sheet secondary structures. It can successfully fold a set of α-helix proteins (Trp-cage and Homeodomain) and β-hairpins (Trpzip-2, GB1 hairpin), which cannot be consistently stabilized by other state-of-the-art force fields. Interestingly, the RSFF1 force field systematically overestimates the melting temperature (and the stability of native state) of these peptides/proteins. It has a potential application in the simulation of protein folding and protein structure refinement.
authors.affiliation: Laboratory of Computational Chemistry and Drug Design, Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School , Shenzhen 518055, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Jiang
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Zhou
authors.forename: Yun-Dong
authors.initials: YD
authors.lastname: Wu
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D004151:Dipeptides / Q000737:chemistry*; D018398:Homeodomain Proteins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008962:Models, Theoretical; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity; D014867:Water / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D004151:Dipeptides; D018398:Homeodomain Proteins; C034284:IgG Fc-binding protein, Streptococcus; D010455:Peptides; D011506:Proteins; C508725:Trp-cage peptide; C539234:Trpzip2 protein; D014867:Water