CLIX: A search algorithm for finding novel ligands capable of binding proteins of known three-dimensional structure

A computer algorithm, CLIX, capable of searching a crystallographic database of small molecules for candidates which have both steric and chemical likelihood of binding a protein of known three‐dimensional structure is presented. The algorithm is a significant advance over previous strategies which consider solely steric or chemical requirements for binding. The algorithm is shown to be capable of predicting the correct binding geometry of sialic acid to a mutant influenzavirus hemagglutinin and of proposing a number of potential new ligands to this protein.