Enhanced sampling and applications in protein folding in explicit solvent.
We report a single-copy tempering method for simulating large complex systems. In a generalized ensemble, the method uses runtime estimate of the thermal average energy computed from a novel integral identity to guide a continuous temperature-space random walk. We first validated the method in a two-dimensional Ising model and a Lennard-Jones liquid system. It was then applied to folding of three small proteins, trpzip2, trp-cage, and villin headpiece in explicit solvent. Within 0.5-1 microsecond, all three systems were reversibly folded into atomic accuracy: the alpha carbon root mean square deviations of the best folded conformations from the native states were 0.2, 0.4, and 0.4 A, for trpzip2, trp-cage, and villin headpiece, respectively.
Zhang
Cheng
C
Department of Bioengineering and Applied Physics Program, Rice University Houston, Texas 77005, USA.
Ma
Jianpeng
J
D000595:Amino Acid Sequence; D008840:Microfilament Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics
D008840:Microfilament Proteins; D010455:Peptides; D011506:Proteins; D012997:Solvents; C508725:Trp-cage peptide; C539234:Trpzip2 protein; C026615:villin