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.

References in corpus (10)

• PLUMED 2: New feathers for an old bird
• PLUMED: a portable plugin for free-energy calculations with molecular dynamics
• A Variational Approach to Enhanced Sampling and Free Energy Calculations
• Enhanced Sampling in the Well-Tempered Ensemble
• Bayesian ensemble refinement by replica simulations and reweighting
• Combining simulations and solution experiments as a paradigm for RNA force field refinement
• Empirical corrections to the Amber RNA force field with Target Metadynamics
• Improved Ab Initio Molecular Dynamics by Minimal Biasing with Experimental Data
• A maximum likelihood algorithm for the estimation and renormalization of exponential densities
• Combining Enhanced Sampling with Experiment Directed Simulation of the GYG peptide

Cited by in corpus (3)

• Infinite Switch Simulated Tempering in Force (FISST)
• Inferring Spatial Source of Disease Outbreaks using Maximum Entropy
• Simulation-Based Inference with Approximately Correct Parameters via Maximum Entropy