Choice of Adaptive Sampling Strategy Impacts State Discovery, Transition Probabilities, and the Apparent Mechanism of Conformational Changes.

ABSTRACT: Interest in atomically detailed simulations has grown significantly with recent advances in computational hardware and Markov state modeling (MSM) methods, yet outstanding questions remain that hinder their widespread adoption. Namely, how do alternative sampling strategies explore conformational space and how might this influence predictions generated from the data? Here, we seek to answer these questions for four commonly used sampling methods: (1) a single long simulation, (2) many short simulations run in parallel, (3) adaptive sampling, and (4) our recently developed goal-oriented sampling algorithm, FAST. We first develop a theoretical framework for analytically calculating the probability of discovering select states on simple landscapes, where we uncover the drastic effects of vary

SUBMITTER: Zimmerman MI 

PROVIDER: S-EPMC6571142 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature