Dewetting transitions in protein cavities

Abstract

In a previous analysis of the solvation of protein active sites, a drying transition was observed in the narrow hydrophobic binding cavity of Cox-2. With the use of a crude metric that often seems able to discriminate those protein cavities that dry from those that do not, we made an extensive search of the PDB, and identified five other proteins that, in molecular dynamics simulations, undergo drying transitions in their active sites. Because such cavities need not desolvate before binding hydrophobic ligands they often exhibit very large binding affinities. This article gives evidence that drying in protein cavities is not unique to Cox-2.