Analytical shape computation of macromolecules: II. Inaccessible cavities in proteins.

The structures of proteins are well-packed, yet they contain numerous cavities which play key roles in accommodating small molecules, or enabling conformational changes. From high-resolution structures it is possible to identify these cavities. We have developed a precise algorithm based on alpha shapes for measuring space-filling-based molecular models (such as van der Waals, solvent accessible, and molecular surface descriptions). We applied this method for accurate computation of the surface area and volume of cavities in several proteins. In addition, all of the atoms/residues lining the cavities are identified. We use this method to study the structure and the stability of proteins, as well as to locate cavities that could contain structural water molecules in the proton transport pathway in the membrane protein bacteriorhodopsin.