ESTIMATION OF BINDING FREE-ENERGIES FOR HIV PROTEINASE-INHIBITORS BY MOLECULAR-DYNAMICS SIMULATIONS

Absolute binding free energies for three inhibitors of HIV-1 proteinas e were estimated from molecular dynamics simulations by a recently rep orted linear approximation procedure. The results were in fairly good agreement,vith experimental binding data. Two of the inhibitors were v ery similar and, for comparison, their relative free energies of bindi ng were also calculated by free energy perturbation methods, giving vi rtually the same result. Effects of cutoff radii and charge states of the protein model were examined. The effects of pH on binding of one o f the inhibitors were predicted.