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:一种探讨HIV-1蛋白酶野生型和I50V V82a和I84V突变的结合和耐药机理机制,用CLL-98065抑制剂与分子动态模拟。

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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:单一突变I50V,V82A和I84V被认为是HIV-1蛋白酶耐药性的关键残留突变。 使用MM-PBSA方法计算的计算绝对结合能量的等级与实验结果很好。 分析焓和熵平衡以解释具有比野生型(WT)复合物更高的熵贡献的I50V和V82a的抵抗力。 减少的范德瓦尔斯能量解释了I84V至GRL-98065的耐药性。 计算GRL-98065和单个蛋白质残留物之间的详细结合能量,以提供抑制剂 - 蛋白质结合和耐药机制的见解。 我们的结果显示,与WT相比,I50V和V82A具有比I84V更大的结构变化。

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