Gaussian Accelerated Molecular Dynamics: Unconstrained Enhanced Sampling and Free Energy Calculation

A Gaussian accelerated molecular dynamics (GaMD) approach for simultaneous enhanced sampling and free energy calculation of biomolecules is presented. By constructing a boost potential that follows Gaussian distribution, accurate reweighting of the GaMD simulations is achieved using cumulant expansion to the second order. Here, GaMD is demonstrated on three biomolecular model systems: alanine dipeptide, chignolin folding, and ligand binding to the T4-lysozyme. Without the need to set predefined reaction coordinates, GaMD enables unconstrained enhanced sampling of these biomolecules. Furthermore, the free energy profiles obtained from reweighting of the GaMD simulations allow us to identify distinct low-energy…

• HH
  Howard Hughes Medical Institute
• NO
  NIH Office of the Director

  Award: DP2-OD007237
• NI
  National Institute of General Medical Sciences

  Awards: GM31749, 1U01GM111528
• DO
  Division of Molecular and Cellular Biosciences

  Award: MCB1020765