title: Ab initio folding of proteins with all-atom discrete molecular dynamics.
abstract: Discrete molecular dynamics (DMD) is a rapid sampling method used in protein folding and aggregation studies. Until now, DMD was used to perform simulations of simplified protein models in conjunction with structure-based force fields. Here, we develop an all-atom protein model and a transferable force field featuring packing, solvation, and environment-dependent hydrogen bond interactions. We performed folding simulations of six small proteins (20-60 residues) with distinct native structures by the replica exchange method. In all cases, native or near-native states were reached in simulations. For three small proteins, multiple folding transitions are observed, and the computationally characterized thermodynamics are in qualitative agreement with experiments. The predictive power of all-atom DMD highlights the importance of environment-dependent hydrogen bond interactions in modeling protein folding. The developed approach can be used for accurate and rapid sampling of conformational spaces of proteins and protein-protein complexes and applied to protein engineering and design of protein-protein interactions.
authors.affiliation: Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.forename: Douglas
authors.initials: D
authors.lastname: Tsao
authors.forename: Huifen
authors.initials: H
authors.lastname: Nie
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Dokholyan
mesh_terms: D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D006860:Hydrogen Bonding; D008840:Microfilament Proteins / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D008840:Microfilament Proteins; C026615:villin