小分子非肽类HIV蛋白酶抑制剂的计算机辅助分子设计

COMPUTER AIDED MOLECULAR DESIGN OF SMALL NONPEPTIDIC HIV 1 PROTEASE INHIBITORS

目的 :探索性研究和设计小分子非肽类HIV蛋白酶抑制剂。方法 :计算机辅助药物设计的分子对接方法。结果 :设计的一系列非肽小分子既有抑制酶的活性 ,又因模拟结合水而具高特异性 ,同时由于去除了肽的性质而提高了口服生物利用度。其中 ,Ppe3j和Bps96 2e可作为候选先导物。 结论 :非肽小分子蛋白酶抑制剂有望成为具有较高口服生物利用度而又不失高活性和高特异性的抗HIV病毒药。

AIM: Studies of small nonpeptidic HIV protease inhibitors based on the 3D structure of the active site of the enzyme. METHODS: Docking algorithm of computer aided molecular design as described in this paper. It is a cycle, consisting of molecular building, energy minimization, auto docking and evaluation of interaction energy, according to the correlation reported lately between the observed in vitro enzyme inhibition and the interaction energy. RESULTS: The series of nonpeptidic small compounds have been modeled and optimized in the binding cavity of HIV protease. Most of the designed molecules in this paper are predicted that they not only inhibit the enzyme, but also have high specificity due to the simulation of bound water. In addition, they seem to have better oral bioavailability for lack of peptide nature. CONCLUSION: Small nonpeptidic molecules are expected to become HIV protease inhibitors with high activity, specificity and good oral bioavailability.