Enhanced Conformational Sampling Using Replica Exchange with Collective-Variable Tempering

J Chem Theory Comput. 2015 Mar 10;11(3):1077-85. doi: 10.1021/ct5009087.

Abstract

The computational study of conformational transitions in RNA and proteins with atomistic molecular dynamics often requires suitable enhanced sampling techniques. We here introduce a novel method where concurrent metadynamics are integrated in a Hamiltonian replica-exchange scheme. The ladder of replicas is built with different strengths of the bias potential exploiting the tunability of well-tempered metadynamics. Using this method, free-energy barriers of individual collective variables are significantly reduced compared with simple force-field scaling. The introduced methodology is flexible and allows adaptive bias potentials to be self-consistently constructed for a large number of simple collective variables, such as distances and dihedral angles. The method is tested on alanine dipeptide and applied to the difficult problem of conformational sampling in a tetranucleotide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / chemistry*
  • Dipeptides / chemistry*
  • Molecular Conformation
  • Molecular Dynamics Simulation*
  • RNA / chemistry*

Substances

  • Dipeptides
  • RNA
  • Alanine