首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Some insights into mechanism for binding and drug resistance of wild type and I50V V82A and I84V mutations in HIV-1 protease with GRL-98065 inhibitor from molecular dynamic simulations.
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Some insights into mechanism for binding and drug resistance of wild type and I50V V82A and I84V mutations in HIV-1 protease with GRL-98065 inhibitor from molecular dynamic simulations.

机译:通过分子动力学模拟,了解了GRL-98065抑制剂与HIV-1蛋白酶中的野生型以及I50V V82A和I84V突变的结合和耐药性的机制。

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摘要

The single mutations I50V, V82A and I84V are considered as the key residue mutations of the HIV-1 protease drug resistance. The rank of calculated absolute binding free energies using MM-PBSA method is in excellent agreement with experimental result. Enthalpic and entropic balance is analyzed to explain resistance in I50V and V82A having a higher entropic contribution than in the wild type (WT) complex. The reduced van der Waals energy explains the drug resistance of I84V to GRL-98065. Detailed binding free energies between GRL-98065 and individual protein residues are calculated to provide insights into the inhibitor-protein binding and drug-resistant mechanism. Our results show I50V and V82A have larger structural changes than I84V compared with WT.
机译:单个突变I50V,V82A和I84V被认为是HIV-1蛋白酶耐药性的关键残基突变。使用MM-PBSA方法计算的绝对结合自由能的等级与实验结果非常吻合。分析了焓和熵的平衡以解释在I50V和V82A中具有比野生型(WT)复合体更高的熵贡献的抗性。降低的范德华能量解释了I84V对GRL-98065的耐药性。计算了GRL-98065与各个蛋白质残基之间的详细结合自由能,以深入了解抑制剂与蛋白质的结合及耐药机制。我们的结果表明,与WT相比,I50V和V82A具有比I84V更大的结构变化。

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