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[摘要]：energy (LIE) method are used here to predict binding modes and affinities for a set of 43 non-nucleoside inhibitors to HIV-1 reverse transcriptase. Starting from a crystallog. structure, the binding modes of 43 inhibitors are predicted using automated docking. The Goldscore scoring function and the LIE method are then used to det. the relative binding free energies for the inhibitors. The Goldscore scoring function does not reproduce the relative binding affinities for the inhibitors, while the std. parametrization of the LIE method reproduces the exptl. binding free energies for 39 inhibitors with an R2 = 0.70 and an unsigned av. error of 0.8 kcal/mol. The present calcns. provide a validation of the combination of docking, MD, and LIE as a powerful tool in structure-based drug design, and the methodol. is easily scalable for attaining a higher throughput of compds. |
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