Hamiltonian Monte Carlo with Constrained Molecular Dynamics as Gibbs Sampling

J Chem Theory Comput. 2017 Oct 10;13(10):4649-4659. doi: 10.1021/acs.jctc.7b00570. Epub 2017 Sep 27.


Compared to fully flexible molecular dynamics, simulations of constrained systems can use larger time steps and focus kinetic energy on soft degrees of freedom. Achieving ergodic sampling from the Boltzmann distribution, however, has proven challenging. Using recent generalizations of the equipartition principle and Fixman potential, here we implement Hamiltonian Monte Carlo based on constrained molecular dynamics as a Gibbs sampling move. By mixing Hamiltonian Monte Carlo based on fully flexible and torsional dynamics, we are able to reproduce free energy landscapes of simple model systems and enhance sampling of macrocycles.