A computational procedure for determining energetically favorable binding sites on biologically important macromolecules

Abstract

The interaction of a probe group with a protein of known structure is computed at sample positions throughout and around the macromolecule, giving an array of energy values. The probes include water, the methyl group, amine nitrogen, carboxy oxygen and hydroxyl. Contour surfaces at appropriate energy levels are calculated for each probe and displayed by computer graphics together with the protein structure. Contours at negative energy levels delineate regions of attraction between probe and protein, and are found at known ligand binding clefts in particular. The contours also enable other regions of attraction to be identified and facilitate the interpretation of protein-ligand energetics. They may be of value for drug design.