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三磷酸腺苷结合盒式转运体的分子模拟
Molecular Simulations of ATP-Binding Cassette Transporters
三磷酸腺苷结合盒式(ATP binding cassete, ABC)转运体是一类与生物体的生理过程和疾病密切相关的膜蛋白,它们利用水解ATP释放的能量实现底物的跨膜转运。虽然研究者已对ABC转运体进行了广泛而深入的研究,但是由于ABC转运体结构的复杂性,导致许多实验技术在ABC转运体的研究中受到较大限制。分子模拟技术可以弥补实验技术的不足,已成为不可或缺的研究工具。本文综述了近年来分子模拟技术同源模建、分子对接和分子动力学模拟在ABC转运体的三维结构模建,底物结合位点确定以及构象转换分子机理的解析等研究领域的最新进展。最后总结了分子模拟技术在ABC转运体研究中所遇到的挑战和拟解决办法。
The ATP-binding cassette (ABC) transporters are integral membrane proteins that can use the energy provided by ATP hydrolysis to actively drive substrates across cell membranes. ABC transporters are linked to many important physiological processes and human diseases. Although many researches have been done, some experimental methods have a lot of restrictions on them because of their complex structures. However, molecular simulations are complements to experimental methods and become indispensable research tools. In this paper, the recent development of the applications of the molecular simulation techniques (e.g., homology modeling, molecular docking and molecular dynamics simulation) on the research of ABC transporters is reviewed. It includes that 3D structures of ABC transporters are built using homology modeling, the binding sites of ABC transporters are identified using molecular docking, and the molecular mechanism of the conformational transition of ABC transporters are probed using molecular dynamics simulations. Finally, the challenges and the developing prospects are proposed and listed at the end of this paper. Contents
1 Introduction
2 Homology modeling of ABC transporters
2.1 Fundamentals of homology modeling
2.2 Building 3D structures of ABC transporters
3 Molecular docking studies of ABC transporters
3.1 Fundamentals of molecular docking
3.2 Molecular docking studies on human P-gp
4 Molecular dynamics simulations of ABC transporters
4.1 Fundamentals of MD simulations
4.2 Conventional MD simulations of ABC transporters
4.3 Targeted MD simulations of ABC transporters
4.4 Steered MD simulations of ABC transporters
5 Conclusions and outlooks
ABC转运体
ABC transporters
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