Iida, S.

Molecular binding sites of a protein tell us how to target the protein from their structural information, which is required for structure-based drug design. However, regardless of their importance, some binding sites, called cryptic binding (CB) sites, are not always readily apparent in the absence of ligands. The identification of CB sites from protein structures remains challenging, and no standard method has been proposed for this purpose. In this study, inspired by the observation of X-ray protein structures with noble gases, particularly xenon, I evaluate a xenon-based CB site identification strategy from their apo states. I performed atomistic molecular dynamics simulations of apo proteins with known CB sites in the presence of xenons. The simulations have revealed that xenons are likely to occupy not only apparent binding sites but also CB sites, implying that they serve as a probe to explore binding sites.