Decomposing the energetic impact of drug-resistant mutations: the example of HIV-1 protease-DRV binding.
Decomposing the energetic impact of drug-resistant mutations: the example of HIV-1 protease-DRV binding.
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分解耐药突变的能量影响：HIV-1 蛋白酶与 DRV 结合的例子。
DOI：
10.1007/978-1-61779-465-0_32
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Schiffer C
中科院分区：
文献类型：
--
作者：
Cai Y;Schiffer C
HIV-1蛋白酶是治疗艾滋病的主要药物靶点。随着耐药HIV-1蛋白酶变体的出现，了解耐药机制变得至关重要。计算方法可以提供更多的细节以外的晶体学和等温滴定量热法的酶结合。Darunavir是FDA最新批准的HIV-1蛋白酶抑制剂。在这种情况下，对与WT蛋白酶和ACT（一种耐药变体）结合的DRV进行自由能分量分析，以评估DRV的每个原子对结合亲和力的贡献。这些信息可以有助于新的HIV-1蛋白酶抑制剂的合理设计。
HIV-1 protease is a major drug target for AIDS therapy. With the appearance of drug-resistant HIV-1 protease variants, understanding the mechanism of drug resistance becomes critical. Computational methods can provide more details about inhibitor-protease binding other than crystallography and isothermal titration calorimetry. Darunavir is the latest FDA approved HIV-1 protease inhibitor. In this context, the free energy component analysis is performed on the DRV binding to WT protease and ACT, a drug resistant variant, to evaluate contribution of each atoms of DRV to the binding affinity. This information can contribute to the rationale design of new HIV-1 protease inhibitors.