Robust Classification of “Relevant” Water Molecules in Putative Protein Binding Sites
Alessio Amadasi, J. Andrew Surface, Francesca Spyrakis, Pietro Cozzini, Andrea Mozzarelli, Glen E. Kellogg · Journal of Medicinal Chemistry · 2008
A statistically validated protocol to identify “relevant” water molecules in protein binding sites using HINT score and a geometric descriptor termed Rank is described. In training, conservation/nonconservation was modeled for 86% of the waters. For the test set, 87% of waters were correctly classified (92% when crystallographic resolution was ≤2.0 Å). Conserved waters make at least two hydrogen bonds with protein and gain 0.6−2.0 kcal mol −1 more binding energy than nonconserved waters.