The SZMAP method computes binding free energies and the corresponding thermodynamic components for water molecules in the binding site of a protein structure [SZMAP, 1.0.0; OpenEye Scientific Software Inc.: Santa Fe, NM, USA, 2011]. In this work, the ability of SZMAP to predict water structure and thermodynamic stability is examined for the X-ray crystal structures of a series of protein–ligand complexes. SZMAP results correlate with higher-level replica exchange thermodynamic integration double decoupling calculations of the absolute free energy of bound waters in the test set complexes. In addition, SZMAP calculations show good agreement with experimental data in terms of water conservation (across multiple crystal structures) and B-factors over a subset of the test set. In particular, the SZMAP neutral entropy difference term calculated at crystallographic water positions within each of the complex structures correlates well with whether that crystallographic water is conserved or displaceable. Further...
['Alexander S. Bayden', 'Demetri T. Moustakas', 'Diane Joseph-McCarthy', 'Michelle L. Lamb']
Evaluating Free Energies of Binding and Conservation of Crystallographic Waters Using SZMAP.