抄録
An alchemical free energy method along a thermodynamic pathway was applied to calculate the binding free energy of theophylline (or caffeine) with an RNA aptamer. To keep the ligand at the binding site during the decoupling of the ligand from the surrounding environment, a distant restraining potential between the ligand's center of mass and the binding site was used. The calculated”absolute” binding affinities are in good agreement with the experimental values. We show that the alchemical free energy calculation is a powerful tool in the realm of rational computational drug design and lead optimization.
