We discuss strategies to improve the sampling of protein conformational space during molecular simulations.   Firstly, it is shown that a principal component analysis of energy-weighted normal modes in Cartesian coordinates can be used to improve the description of the dynamics of protein substructures.   The method can operate with either atomistic or coarse-grained models of the protein.  An implicit reverse coarse-graining allows the dynamics of all-atoms to be recovered when a coarse-grained model is used. Secondly, we present methods of harmonic vibrational analysis in delocalised internal coordinates.   It is shown that long-rangeinternal coordinates may be especially suitable for describing low frequency global deformation modes in proteins. The methods presented here are expected to be useful in protein-ligand and protein-protein docking and in biasing molecular dynamics simulations.

Predicting large-scale conformational changes in proteins using harmonic vibrational analyses

241st National Meeting (2011)

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