This approach thus received a continuous interest on account of its prime importance for lead discovery or lead optimization, but it was recently largely boosted up with the development of huge chemical databases and the need for efcient tools in highthroughput virtual screening. Determining, ab initio, the molecules the most able to tightly bind a specic target is of great interest for prioritizing synthesis of the putative most active (potential) new drugs and avoids wasting time and money on compounds that will reveal uninteresting for the practical application looked for.