title: Folding Trp-cage to NMR resolution native structure using a coarse-grained protein model.
abstract: We develop a coarse-grained protein model with a simplified amino acid interaction potential. Using this model, we perform discrete molecular dynamics folding simulations of a small 20-residue protein--Trp-cage--from a fully extended conformation. We demonstrate the ability of the Trp-cage model to consistently reach conformations within 2-angstroms backbone root-mean-square distance from the corresponding NMR structures. The minimum root-mean-square distance of Trp-cage conformations in simulations can be <1 angstroms. Our findings suggest that, at least in the case of Trp-cage, a detailed all-atom protein model with a molecular mechanics force field is not necessary to reach the native state of a protein. Our results also suggest that the success of folding Trp-cage in our simulations and in the reported all-atom molecular mechanics simulation studies may be mainly due to the special stabilizing features specific to this miniprotein.
authors.affiliation: Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina 27599, USA. fding@unc.edu
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Buldyrev
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Dokholyan
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001703:Biophysics / Q000379:methods*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D010455:Peptides; D011506:Proteins; C508725:Trp-cage peptide; D014364:Tryptophan; D011392:Proline