Distribution of water around L-amino acid side chains: Computational and statistical analysis

The structure of water around proteins makes significant contributions to protein folding and stability, as well as function. Furthermore, knowledge of water structure is important for refining protein structures determined by X-ray and neutron diffraction analyses. Knowledge of structural propensities for water in protein crystals can thus provide further insights into protein structure and dynamics, as well as additional parameters for refinement in diffraction analyses, which ultimately improves the accuracy of derived molecular models. In the present work, stable conformations of water molecules around amino acid side chains have been calculated using density functional theory. Actual distributions of water molecules around amino acid side chains have also been mined from a validated, non-redundant subset of the Protein Data Bank, compiled as of March 2004. We present the results from these theoretical calculations and statistical analyses, which show strong agreement for the distances, locations, as well as orientations of water molecules around the 20 L-amino acid side chains. These distribution data suggest that water structures around amino acid side chains exhibit propensities that can be used for gaining deeper functional insights, as well as to parameterize and improve refinement in both X-ray and neutron diffraction analyses.