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We have carried out a large-scale biomolecular quantum chemical computation on the complexes of HIV-1 protease with six different peptidomimetic HIV-1 inhibitors by employing the ab initio fragment molecular orbital (FMO) method at MP2/6-31G calculation level, in order to clarify a relationship between the computed binding energy ΔE for the HIV-1 protease complexes and the clinically measured pharmacokinetic parameters such as maximum drug concentration (Cmax) and area under the drug concentration-time curve (AUC), both of which may be used as indications for drug effects of HIV-1 inhibitors. The FMO calculations indicate that the inhibitor bearing a negatively large binding energy has relatively large values of Cmax and AUC. In addition, similar FMO computations on the complexes of a human protease renin with two HIV-1 protease inhibitors, Ritonavir and Saquinavir, show that the binding energy for Ritonavir with many side effects is negatively larger than that for Saquinavir with few side effects.
Research papers (academic journals)
