G. De FABRITIIS
Computational Biochemistry and Biophysics Lab (GRIB-IMIM/UPF), Barcelona Biomedical Research Park (PRBB), C/Dr Aiguader 88, 08003 Barcelona, Spain
J. VILLÀ-FREIXA
Computational Biochemistry and Biophysics Lab (GRIB-IMIM/UPF), Barcelona Biomedical Research Park (PRBB), C/Dr Aiguader 88, 08003 Barcelona, Spain
P. V. COVENEY
Centre for Computational Science, Department of Chemistry, University College London, 20 Gordon street, London WC1H 0AJ, United Kingdom

Permeation of small molecules across membrane channels can be measured by a multiscale computational protocol based on Brownian dynamics and the potential of mean force formalism. In this article we look at ways to compute the potential of mean force by reusing pre-existing molecular dynamics trajectories via a protocol centered on instantaneous forward/reverse transformations. We apply the method to the energetics of water across the narrow channel formed by Gramicidin A and reproduce several features of the energy barrier across the channel albeit at a coarse level of detail due to limits imposed by the exponential averages intrinsic to the method and the small size of the channel. The implications for ions and less dense systems are briefly discussed.

Multiscale modelling; forward-reverse transformations; potential of mean force