Bespoke Bias for Obtaining Free Energy Differences within Variationally Enhanced Sampling

J McCarty and O Valsson and M Parrinello, JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 12, 2162-2169 (2016).

DOI: 10.1021/acs.jctc.6b00125

Obtaining efficient sampling of multiple metastable states through molecular dynamics and hence determining free energy differences is central for understanding many important phenomena. Here we present a new biasing strategy, which employs the recent variationally enhanced sampling approach (Valsson and Parrinello Phys. Rev. Lett. 2014, 113, 090601). The bias is constructed from an intuitive model of the local free energy surface describing fluctuations around metastable minima and depends on only a few parameters which are determined variationally such that efficient sampling between states is obtained. The bias constructed in this manner largely reduces the need of finding a set of collective variables that completely spans the conformational space of interest, as they only need to be a locally valid descriptor of the system about its local minimum. We introduce the method and demonstrate its power on two representative examples.

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