EFFECTIVE METHODS FOR ESTIMATION OF BINDING-ENERGIES IN COMPUTER-AIDED DRUG DESIGN

The development of an efficient and accurate method for computer-aided drug design presents a major challenge for computational chemistry. T he present work addresses this challenge by examining the accuracy and speed of several alternative strategies. Previous studies of the bind ing of ligands to the MC603 antibody and new studies of ligand binding to endothiapepsin are considered. It is found that the semimacroscopi c version of the Protein Dipoles Langevin Dipoles method (the PDLD/S m ethod) approach can provide qualitative results with reasonable execut ion times. Much more time is required for the linear response approxim ation, although it yields accurate results in some cases. Overall, it is still not clear what generation of computers will be needed for rel iable and fast drug screening. Nevertheless, computer simulation is cl early useful for correlation X-ray structures of enzyme-inhibitor comp lexes with the corresponding binding energies.