SiteAlign: a simple and fuzzy method to measure similarity between binding sites

A novel method to measure distances between druggable protein cavities is presented . Starting from user-defined ligand binding sites, a set of eight topological and physicochemical properties are projected from cavity-lining protein residues to an 80 triangle-discretised sphere placed at the centre of the binding site, thus defining a cavity fingerprint. Representing binding site properties onto a discretised sphere presents many advantages: (i) a normalised distance between binding sites of different sizes may be easily derived by summing up the normalised differences between the 8 computed descriptors; (ii) a structural alignment of two proteins is simply done by systematically rotating/translating one mobile sphere around one immobile reference; (iii) a certain degree of fuzziness in the comparison is reached by projecting global amino acid properties (e.g., charge, size, functional groups count, distance to the site centre) independently of local rotameric/tautomeric states of cavity-lining residues.