Design of a Molecular Dynamics Model for High-Performance Computing of Conformational Changes in Microtubule Protofilaments Associated with the Anticancer Drug Taxol

V. Fedorov, E. G. Kholina, M. Bulatov, I. Kovalenko
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Abstract

Molecular dynamics models of tubulin tetramers in complex with the anticancer drug taxol were created based on high-resolution spatial structures (PDB ID 3J6G). We tested performance of various computational architectures in molecular dynamics calculations of tubulin tetramers. We revealed the optimal computer architecture and carried out three 1 μs molecular dynamic trajectories of taxol-bound tubulin tetramer. We analyzed the conformational flexibility of tubulin tetramers in a complex with taxol, calculated the Euler angles for intra- and inter-dimer interfaces of the protofilament, as well as the degree and direction of protofilament bending. The stiffness of protofilaments was studied using the energy equipartition theorem. The results allowed us to conclude that taxol binding reduces stiffness at both the inter- and intra-dimer interfaces, which may facilitate the process of microtubule assembly.
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抗癌药物紫杉醇相关微管原丝构象变化的高性能计算分子动力学模型设计
基于高分辨率空间结构(PDB ID 3J6G)建立了微管蛋白四聚体与抗癌药物紫杉醇复合物的分子动力学模型。我们测试了各种计算架构在微管蛋白四聚体分子动力学计算中的性能。我们设计了最优的计算机结构,并对紫杉醇结合的微管蛋白四聚体进行了3个1 μs的分子动力学轨迹。我们分析了微管蛋白四聚体在紫杉醇配合物中的构象柔韧性,计算了原丝内和间二聚体界面的欧拉角,以及原丝弯曲的程度和方向。利用能量均分定理研究了原丝的刚度。结果表明,紫杉醇的结合降低了二聚体之间和内部界面的刚度,这可能有助于微管的组装过程。
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来源期刊
Mathematical Biology and Bioinformatics
Mathematical Biology and Bioinformatics Mathematics-Applied Mathematics
CiteScore
1.10
自引率
0.00%
发文量
13
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