Presidential Faculty Fellows Program (PFF/PECASE): Role of Electrostatic Forces in Protein Stability and Functions

Gunner蛋白的结构是由蛋白质的环境和初级序列决定的。蛋白质的功能通常需要蛋白质的运动。这可能涉及小的、局部的变化，或者可能需要几个不同的、低能量的蛋白质状态。可分离蛋白状态的相对能量通常由配体的浓度决定。结合配体可引起结合亲和力（如血红蛋白（O2））、催化速率（如细胞表面受体（结合配体））、蛋白间结合（如钙调素（Ca+2））或质子结合（光合反应中心（电子转移））的变化。本研究的目的是确定配体或离子的结合如何改变不同结构的自由能，重点研究了磷酸盐、钙、质子和电子等带电效应器的结合。接下来的目标是分析控制三种蛋白质载体质子转移的机制，这三种蛋白质的结构已经被原子分辨率解决了：细胞色素氧化酶，bc1复合物和质子三磷酸腺苷酶。蛋白质是一组生物分子，它们进行化学反应，将我们的食物转化为有用的能量。这些能量随后被生物体中不同的蛋白质用来完成工作，比如为细胞生长构建新的分子。蛋白质的形状决定了它的功能。通过改变形状，可以打开或关闭一个进程。虽然蛋白质太过复杂，无法用基本物理定律完全分析，但蛋白质的计算机建模可以用来询问自然界中哪些力对形成我们所看到的结构最重要。在许多蛋白质中，当一小群蛋白质结合时，它的结构会在两种不同的形状之间变化。这项工作的目的是探索结合带电基团是如何改变结构的。

9629047 Gunner Protein structures are determined by the protein's environment as well as its primary sequence. Protein function often demands protein movement. This can involve small, delocalized changes or may require several distinct, low energy protein states. The relative energy of separable protein states is often determined by the concentration of ligand. Binding the ligand can induce a change in binding affinity (e.g. hemoglobin (( O2), catalysis rate (e.g. cell surface receptors ( bound ligand), inter-protein association (e.g. calmodulin ( Ca+2), or proton binding (photosynthetic reaction centers ( electron transfer). The objective of the research is to determine how binding of ligand or ion can modify the free energy of different structures, focusing on the binding of charged effectors such as phosphate, calcium, protons, and electrons. The goal will then be to analyze the mechanism that controls vectorial proton transfer in three proteins whose structures have been solved to atomic resolution: the cytochrome oxidase, the bc1 complex, and the proton ATPase. Proteins are the group of biological molecules that carry out chemical reactions to transform our food to useful energy. This energy is then used by different proteins in the organism to carry out work, such as building new molecules for cell growth. The shape of the protein determines what it can do. By changing the shape, a process can be turned on or off. While proteins are far too complex to be analyzed completely with the basic laws of physics, computer modeling of proteins can be used to ask what forces in nature are the most important for making the structure that is seen. In many proteins, when a small group is bound, it's structure changes between two distinct shapes. The goal of this work is to explore how binding a charged group changes the structure.