title: Exploring the parameter space of the coarse-grained UNRES force field by random search: selecting a transferable medium-resolution force field.
abstract: We explored the energy-parameter space of our coarse-grained UNRES force field for large-scale ab initio simulations of protein folding, to obtain good initial approximations for hierarchical optimization of the force field with new virtual-bond-angle bending and side-chain-rotamer potentials which we recently introduced to replace the statistical potentials. 100 sets of energy-term weights were generated randomly, and good sets were selected by carrying out replica-exchange molecular dynamics simulations of two peptides with a minimal alpha-helical and a minimal beta-hairpin fold, respectively: the tryptophan cage (PDB code: 1L2Y) and tryptophan zipper (PDB code: 1LE1). Eight sets of parameters produced native-like structures of these two peptides. These eight sets were tested on two larger proteins: the engrailed homeodomain (PDB code: 1ENH) and FBP WW domain (PDB code: 1E0L); two sets were found to produce native-like conformations of these proteins. These two sets were tested further on a larger set of nine proteins with alpha or alpha + beta structure and found to locate native-like structures of most of them. These results demonstrate that, in addition to finding reasonable initial starting points for optimization, an extensive search of parameter space is a powerful method to produce a transferable force field.
authors.affiliation: Biomolecular Physics and Modeling Group, School of Physics, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: He
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.forename: Adam
authors.initials: A
authors.lastname: Liwo
authors.forename: Harold A
authors.initials: HA
authors.lastname: Scheraga
mesh_terms: D003198:Computer Simulation; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
chemical_list: D010455:Peptides; D014364:Tryptophan