Computational studies of membrane transport proteins

次级活性转运蛋白是一类存在于细胞膜中的蛋白质。它们利用分子浓度的现有差异作为能量来源，使其他物质（如营养物质或神经递质）逆着自然流动而移动。这个过程需要蛋白质改变以暴露一条通路，该通路允许物质在膜的一侧或另一侧结合，这是一个称为交替进入的重复循环。每种生物体都含有几十种不同类型的转运蛋白。它们有各种各样的设计，但它们都有一种内部的对称模式。最近的发现来自于对它们的3D形状的观察，这些形状是近年来才出现的。然而，为了真正了解每个转运蛋白是如何工作的，以及它如何受到周围环境的影响，我们需要更多地了解它可以变形的不同形状，以及它在哪里结合它所移动的物质。此外，这些蛋白质的起始和末端区域在细胞控制其运输行为中起重要作用，这些区域具有高度灵活性，因此需要额外的努力来表征。 我们小组正在进行的研究继续调查这些问题，在几个不同的膜蛋白，包括血清素转运蛋白SERT，甜菜碱同向转运蛋白BetP和线粒体丙酮酸载体MPC，使用先进的结构预测技术和分子动力学模拟。这些工作正在与实验室合作进行，以促进对膜运输和调节机制的理解。

Secondary active transporters are a class of proteins found in cell membranes. They use existing differences in the concentration of molecules as a source of energy to move other substances, like nutrients or neurotransmitters, against their natural flow. This process requires the protein to change to expose a pathway that allows the substance to bind on one or other side of the membrane, in a repeating cycle called alternating access. Every organism contains dozens of different types of these transporter proteins. They have various designs, but they all have a kind of internal pattern of symmetry. Recent discoveries have come from looking at their 3D shapes, which have only been accessible in recent years. Nevertheless, to truly understand how each transporter works and how it is affected by its surroundings, we need to know more about the different shapes it can morph into and where it binds the substances it moves. Moreover, regions at the start and end of these protein that play important roles in cellular control of their transport behaviors are highly flexible and therefore require additional effort to characterize. Ongoing studies from our group have continued to investigate these questions in several different membrane proteins, including serotonin transporter SERT, the betaine symporter BetP, and mitochondrial pyruvate carrier MPC, using advanced structure prediction techniques and molecular dynamics simulations. These efforts are being carried out in collaboration with experimental laboratories, to drive understanding of the mechanism of membrane transport and regulation.