Methods and systems are described for identification and characterization of allosteric sites in proteins and enzyme molecules. The disclosed methods allow for identification of natural and true binding sites on surface regions of protein and enzyme molecules by following the pathways of energy flow between the activity center to the surface regions. Allosteric sites are identified and ranked for their effect on target activity of the protein using computational methods. Then chemical libraries are screened to find the best candidates for drug like molecules that affect target activity of the protein or enzyme.