Using sketch-map coordinates to analyze and bias molecular dynamics simulations

Gareth A. Tribello, Michele Ceriotti, Michele Parrinello

Research output: Contribution to journalArticle

84 Citations (Scopus)
237 Downloads (Pure)

Abstract

When examining complex problems, such as the folding of proteins, coarse grained descriptions of the system drive our investigation and help us to rationalize the results. Oftentimes collective variables (CVs), derived through some chemical intuition about the process of interest, serve this purpose. Because finding these CVs is the most difficult part of any investigation, we recently developed a dimensionality reduction algorithm, sketch-map, that can be used to build a low-dimensional map of a phase space of high-dimensionality. In this paper we discuss how these machine-generated CVs can be used to accelerate the exploration of phase space and to reconstruct free-energy landscapes. To do so, we develop a formalism in which high-dimensional configurations are no longer represented by low-dimensional position vectors. Instead, for each configuration we calculate a probability distribution, which has a domain that encompasses the entirety of the low-dimensional space. To construct a biasing potential, we exploit an analogy with metadynamics and use the trajectory to adaptively construct a repulsive, history-dependent bias from the distributions that correspond to the previously visited configurations. This potential forces the system to explore more of phase space by making it desirable to adopt configurations whose distributions do not overlap with the bias. We apply this algorithm to a small model protein and succeed in reproducing the free-energy surface that we obtain from a parallel tempering calculation.

Original languageEnglish
Pages (from-to)5196-5201
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number14
DOIs
Publication statusPublished - 03 Apr 2012

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