Seminar
Ab initio molecular dynamics studies of targets for anti-AIDS therapy
Dr. Paolo CarloniInternational School for Advanced Studies
Trieste,
Italy
Friday, June 4, 1999
3:00 pm
3269 Beckman Institute
Molecular dynamics calculations based on force-fields are a very useful tool for designing more powerful drugs and for improving our understanding of molecular similarity and pharmacophores. However, the force-field approach is not devoid of problems, which lie in the complex physical-chemistry of the intermolecular interactions. Indeed, it is becoming increasingly clear, from both experiment and theory, that quantum-mechanical effects can be very important in ligand-receptor interactions and enzyme-inhibitor binding. Here we will report recent findings from our studies on targets for anti-AIDS drugs, the HIV-1 protease and HIV-1 reverse transcriptase enzymes. Our calculations, based on the density functional theory/molecular dynamics (Car-Parrinello) method, suggest that bond-forming - bond-breaking processes (such as the low-barrier hydrogen bonds) and charge transfer effects play an important role for the enzymatic function and for the binding of drugs.
