Proteins function in an aqueous environment and are evolutionarily adapted to it. Water molecules represent an integral part of protein molecules and a key determinant of protein structure, dynamics and function. Protein-water interactions govern various processes, including protein folding, enzymatic catalysis, and molecular recognition. Water does not simply fill up the available space around proteins, but occupies specific sites and forms localized clusters, determined by its hydrogen-bonding capabilities. Here we present the newly developed “Atlas of Protein Hydration” [1]. The atlas provides statistical overview of the first hydration shell of amino acid residues in different conformational states in X-ray crystal structures, and also visualization of water distribution and the location of the preferred hydration sites using JSmol applet. The positions and probabilities of the hydration sites were derived from the analysis of of a non-redundant set of 2818 high resolution protein crystal structures from the Protein Data Bank, as described in ref. [2]. Besides the crystal-based data, the atlas also contains information derived from ab initio quantum mechanics calculations. For each hydration site the position was optimized and interaction energy was calculated at the level of DFT-D (RI-TPSS/TZVP augmented with empirical dispersion term) with the solvation effects described using COSMO. These calculations show that the majority of hydration sites are located in local energy minima. The calculated interaction energies help to assess the preference of water for the individual hydration sites.
The atlas of conformation-specific hydration of amino acid residues in proteins could find applications in the development of more precise water placement algorithms in structural bioinformatics areas such as crystallographic refinement, protein structure prediction, computational drug design and protein-protein docking. The Atlas of Protein Hydration website is available at www.dnatco.org/atlas.