Enhanced sampling and applications in protein folding in explicit solvent

Abstract

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 folded into atomic accuracy: the alpha carbon root mean square deviations of the best folded conformations from the native states were 0.2 A, 0.4 A, and 0.4 A, for trpzip2, trp-cage, and villin headpiece, respectively.

60 pages, 13 figures

References in corpus (4)

• Canonical sampling through velocity-rescaling
• Simulation via Direct Computation of Partition Functions
• Enhanced sampling in generalized ensemble with large gap of sampling parameter: case study in temperature space random walk
• Unbiased estimators for spatial distribution functions of classical fluids

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