Computational investigations on the dynamic binding effect of molecular tweezer CLR01 toward intrinsically disordered HIV-1 Nef,Biotechnology and Applied Biochemistry

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Computational investigations on the dynamic binding effect of molecular tweezer CLR01 toward intrinsically disordered HIV-1 Nef
Biotechnology and Applied Biochemistry ( IF 3.2 ) Pub Date : 2020-05-24 , DOI: 10.1002/bab.1957
Anil Bhattarai ₁ , Isaac Arnold Emerson ₁

Affiliation

Intrinsically disordered proteins (IDPs) are highly flexible molecules that undergo disorder to order transition through their interaction with other molecules. IDPs play a vital role in several biological processes ranging from molecular recognition to several human diseases through the protein–protein interaction. The dynamic flexibility of IDPs and their implications in several human diseases enable these molecules to serve as novel therapeutic targets. However, the challenging task is to develop novel drugs against IDPs because of their lack of stable structures and the nature of high conformational flexibility. In this study, we have calculated the dynamic binding effect of the supramolecular tweezer CLR01 against the intrinsically disordered HIV-1 Nef by employing molecular docking and dynamics simulation approaches. From docking results, we predicted the strong binding affinity of the tweezer with the target residues of Nef. The docking results were further validated from the molecular dynamics simulation studies confirming the conformational stability of Nef upon tweezer binding. These findings provide useful insights into the development of potent inhibitors for targeting Nef protein functions.

中文翻译：

分子镊子CLR01对内在紊乱的HIV-1 Nef的动态结合效应的计算研究

本质无序蛋白 (IDP) 是高度灵活的分子，它们通过与其他分子的相互作用经历无序到有序的转变。IDP 在多种生物过程中发挥着至关重要的作用，从分子识别到通过蛋白质-蛋白质相互作用的多种人类疾病。IDP 的动态灵活性及其在几种人类疾病中的影响使这些分子成为新的治疗靶点。然而，具有挑战性的任务是开发针对 IDP 的新型药物，因为它们缺乏稳定的结构和高构象灵活性的性质。在这项研究中，我们通过分子对接和动力学模拟方法计算了超分子镊子 CLR01 对内在紊乱的 HIV-1 Nef 的动态结合效应。从对接结果来看，我们预测了镊子与 Nef 目标残基的强结合亲和力。分子动力学模拟研究进一步验证了对接结果，证实了镊子结合后 Nef 的构象稳定性。这些发现为开发针对 Nef 蛋白功能的有效抑制剂提供了有用的见解。

更新日期：2020-05-24

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