Identification of protein stability patches that pinpoint key structural or functional sites

The ability to locate in silico, in a protein structure, the active site, the binding site or the initiation site of conformational changes is important for understanding the functional mechanisms and is a prerequisite for the rational prediction of targeted mutations or for protein design. The amino acids in these sites have been optimized during evolution to fulfill a specific function, but not necessarily to improve stability. We present a program able to detect residues that are optimal or non-optimal against thermodynamic stability and to group them into patches. We apply this program to bovine seminal ribonuclease, a member of a well-studied enzyme family that binds RNA and undergoes 3D domain swapping under certain conditions.