Computational studies of membrane transport proteins

次级活性转运蛋白是在细胞膜上发现的一类蛋白质。它们利用现有的分子浓度差异作为能量来源来移动其他物质，如营养物质或神经递质，以对抗它们的自然流动。这一过程需要蛋白质改变，从而暴露出一条途径，使物质能够结合在膜的一边或另一边，在一个被称为交替进入的重复循环中。每个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对称的图案。最近的发现来自于观察它们的三维形状，这是近年来才得以实现的。然而，为了真正理解每个转运体是如何工作的，以及它是如何受到周围环境的影响的，我们需要更多地了解它可以变形成的不同形状，以及它在哪里与它所移动的物质结合。此外，这些蛋白的起始和末端在细胞控制其转运行为中起重要作用的区域是高度灵活的，因此需要额外的努力来表征。

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.