Accurate calculation of side chain packing and free energy with applications to protein molecular dynamics.

ABSTRACT: To address the large gap between time scales that can be easily reached by molecular simulations and those required to understand protein dynamics, we present a rapid self-consistent approximation of the side chain free energy at every integration step. In analogy with the adiabatic Born-Oppenheimer approximation for electronic structure, the protein backbone dynamics are simulated as preceding according to the dictates of the free energy of an instantaneously-equilibrated side chain potential. The side chain free energy is computed on the fly, allowing the protein backbone dynamics to traverse a greatly smoothed energetic landscape. This computation results in extremely rapid equilibration and sampling of the Boltzmann distribution. Our method, termed Upside, employs a reduced model invol

SUBMITTER: Jumper JM 

PROVIDER: S-EPMC6307715 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature