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

9629047 Gunner蛋白质结构由蛋白质的环境以及其一级序列决定。 蛋白质功能通常需要蛋白质运动。 这可能涉及小的，离域的变化，或可能需要几个不同的，低能量的蛋白质状态。 蛋白质可分离态的相对能量通常由配体的浓度决定。 结合配体可以诱导结合亲和力（例如血红蛋白（（O2））、催化速率（例如细胞表面受体（结合配体）、蛋白质间缔合）的变化 (e.g.钙调素（Ca+2）或质子结合（光合反应中心（电子传递））。 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，重点是带电效应物如磷酸盐、钙、质子和电子的结合。 然后，目标将是分析的机制，控制矢量质子转移的三种蛋白质，其结构已解决原子分辨率：细胞色素氧化酶，bc1复合物，和质子ATP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。 然后，这种能量被生物体中的不同蛋白质用来进行工作，例如为细胞生长构建新分子。 蛋白质的形状决定了它能做什么。 通过更改形状，可以打开或关闭进程。 虽然蛋白质太复杂，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什么力量对形成所看到的结构最重要。 在许多蛋白质中，当一个小基团结合时，它的结构会在两种不同的形状之间变化。 这项工作的目标是探索如何结合带电基团改变结构。

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.