Multiscale methods for macromolecular simulations

Abstract

Summary In this article we review the key modelling tools available for simulating biomolecular systems. We consider recent developments and representative applications of mixed quantum mechanics / molecular mechanics (QM/MM), Elastic Network Models (ENM), coarse-grained molecular dynamics and grid based tools for calculating interactions between essentially rigid protein assemblies. We consider how the different length scales can be coupled, both in a sequential fashion (e.g. a coarse-grained or grid model using parameterisation from MD simulations), and via concurrent approaches, where the calculations are performed together and together control the progress of the simulation. We suggest how the concurrent coupling approach familiar in the context of QM/MM calculations can be generalised, and describe how this has been done in the CHARMM macromolecular simulation package.