Efficient potential of mean force calculation from multiscale simulations: Solute insertion in a lipid membrane

Abstract

The determination of potentials of mean force for solute insertion in a lipid membrane by means of all-atom molecular dynamics simulations is often hampered by sampling issues. Recently, a multiscale method has been proposed to leverage the conformational ensemble of a lower-resolution model as starting point for higher resolution simulations. In this work, we analyze the efficiency of this method by comparing its predictions for propanol insertion into a lipid membrane against conventional atomistic umbrella sampling simulation results. The multiscale approach is confirmed to provide accurate results with a gain of one order of magnitude in computational time. We then investigate the role of the coarse-grained representation. We find that the accuracy of the results is tightly connected to the presence of a good configurational overlap between the coarse-grained and atomistic models-a general requirement when developing multiscale simulation methods.

Keywords: Drug-membrane systems; Enhanced sampling; Multiscale simulations; Potential of mean force.