Recent Advances in Maximum Entropy Biasing Techniques for Molecular Dynamics

Abstract

This review describes recent advances by the authors and others on the topic of incorporating experimental data into molecular simulations through maximum entropy methods. Methods which incorporate experimental data improve accuracy in molecular simulation by minimally modifying the thermodynamic ensemble. This is especially important where force fields are approximate, such as when employing coarse-grain models, or where high accuracy is required, such as when attempting to mimic a multiscale self-assembly process. The authors review here the experiment directed simulation (EDS) and experiment directed metadynamics (EDM) methods that allow matching averages and distributions in simulations, respectively. Important system-specific considerations are discussed such as using enhanced sampling simultaneously, the role of pressure, treating uncertainty, and implementations of these methods. Recent examples of EDS and EDM are reviewed including applications to ab initio molecular dynamics of water, incorporating environmental fluctuations inside of a macromolecular protein complex, improving RNA force fields, and the combination of enhanced sampling with minimal biasing to model peptides.

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• PLUMED: a portable plugin for free-energy calculations with molecular dynamics
• A Variational Approach to Enhanced Sampling and Free Energy Calculations
• Combining simulations and solution experiments as a paradigm for RNA force field refinement
• Improved Ab Initio Molecular Dynamics by Minimal Biasing with Experimental Data