Estimation of binding free energies for HIV proteinase inhibitors by molecular dynamics simulations

Absolute binding free energies for three inhibitors of HIV–1proteinase were estimated from molecular dynamics simulationsby a recently reported linear approximation procedure. The resultswere in fairly good agreement with experimental binding data.Two of the inhibitors were very similar and, for comparison,their relative free energies of binding were also calculatedby free energy perturbation methods, giving virtually the sameresult Effects of cutoff radii and charge states of the proteinmodel were examined. The effects of pH on binding of one ofthe inhibitors were predicted.