Pant Shashank, Dehghani-Ghahnaviyeh Sepehr, Trebesch Noah, Rasouli Ali, Chen Tianle, Kapoor Karan, Wen Po-Chao, Tajkhorshid Emad
Theoretical and Computational Biophysics Group, NIH Resource for Macromolecular Modeling and Visualization, Beckman Institute for Advanced Science and Technology, Department of Biochemistry, and Center for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, Illinois 61801-3028, United States.
J Phys Chem B. 2025 Apr 17;129(15):3703-3719. doi: 10.1021/acs.jpcb.5c00104. Epub 2025 Mar 18.
Membrane transporters are integral membrane proteins that act as gatekeepers of the cell, controlling fundamental processes such as recruitment of nutrients and expulsion of waste material. At a basic level, transporters operate using the "alternating access model," in which transported substances are accessible from only one side of the membrane at a time. This model usually involves large-scale structural changes in the transporter, which often cannot be captured using unbiased, conventional molecular simulation techniques. In this article, we provide an overview of some of the major simulation techniques that have been applied to characterize the structural dynamics and energetics involved in the transition of membrane transporters between their functional states. After briefly introducing each technique, we discuss some of their advantages and limitations and provide some recent examples of their application to membrane transporters.
膜转运蛋白是整合膜蛋白，充当细胞的守门人，控制着诸如营养物质摄取和废物排出等基本过程。在基本层面上，转运蛋白利用“交替 access 模型”运作，即被转运物质在任何时刻仅能从膜的一侧被接触到。该模型通常涉及转运蛋白的大规模结构变化，而使用无偏差的传统分子模拟技术往往无法捕捉到这些变化。在本文中，我们概述了一些主要的模拟技术，这些技术已被应用于表征膜转运蛋白在其功能状态转变过程中所涉及的结构动力学和能量学。在简要介绍每种技术之后，我们讨论了它们的一些优点和局限性，并提供了它们应用于膜转运蛋白的一些最新实例。
