Thermodynamics and Kinetics of Electron and Proton Transfers in Proton Pumping Proteins

膜包围着细胞和细胞室。这些膜使细胞能量的动态和重要储存成为可能，这是一种跨膜质子梯度，即一种情况（类比于电池），在充满能量的膜的一边有更多的质子，而另一边更少。来自食物或光的能量（在光合作用中）可以用来制造这种质子电池，它可以有效地为细胞提供燃料。该研究项目将研究一类蛋白质（血红素铜氧化酶），其中包括使用大气氧气作为燃料的细胞色素c氧化酶。血红素铜氧化酶蛋白通过一种在生物学中被称为质子泵的常见而重要的机制来帮助构建梯度，质子在一个非导电膜上向一个方向移动，从而构建跨膜质子梯度。这项研究的目的是更好地理解质子泵送蛋白的设计特征，这也将有助于设计专门的半透膜，如电化学电池（包括电池）所需的半透膜。该项目汇集了对细胞生物学、质子泵送过程的化学反应和带电质子运动的物理学的研究。这项工作将培养跨学科科学领域的研究生、本科生和博士后。这个项目的目标是从已知的血红素铜氧化酶蛋白的原子位置开始进行计算机模拟。虽然没有任何蛋白质中质子泵送的详细模型，但有一个大致的轮廓构成了研究的基础。计算将寻找蛋白质的区域，当质子在蛋白质中移动时，这些区域可以为质子提供停止点。此外，质子必须通过由充满水分子的通道组成的途径穿过蛋白质。这些途径将被识别和研究，以确定在哪里可以形成阻塞，以阻止质子向后移动，从而消散质子梯度。这里使用的计算方法是不断发展的最先进的技术，它们将通过这些计算进行测试和改进。该项目由生物科学理事会分子和细胞生物科学司的分子生物物理学小组共同资助；物理学部的生命系统物理学项目，以及数学和物理科学理事会化学学部的生命过程化学项目。

Membranes surround cells and cellular compartments. These membranes make possible a dynamic and important storehouse of cellular energy, which is a transmembrane proton gradient, i.e. a situation (by analogy to a battery) in which there are more protons on one side of an energized membrane and fewer on the other. Energy from food or light (in photosynthesis) can be used to make this proton battery, which efficiently fuels the cell. This research program will study a class of proteins (Heme Copper Oxidases), which includes Cytochrome c oxidase that uses atmospheric oxygen as a fuel. The Heme Copper Oxidase proteins help build the gradient by a common and important mechanism in biology called proton pumping, which moves protons in one direction across a non-electrically conducting membrane, thereby constructing a transmembrane proton gradient. The objective of this research is to better understand the design features of proton-pumping proteins, which will also help in the design of specialized semi-permeable membranes such as those needed for electrochemical cells (which include batteries). The project brings together the study of the biology of the cell, of the chemistry of the reactions that fuel the proton pumping process and of the physics of the motion of the charged protons. The work will train graduate and undergraduate students and postdoctoral fellows in interdisciplinary science.The objective of this project is to carry out computer simulations starting with the known positions of the atoms in the Heme Copper Oxidase proteins. While there is no detailed model for proton pumping in any protein, there is a general outline that forms the basis of the research. The calculations will look for regions of the protein that can provide stopping points for the proton as it moves across the protein. In addition, protons must move through the protein via pathways that can be made up of channels filled with water molecules. These pathways will be identified and studied to see where blockages can be formed to keep the protons from moving backwards to dissipate the proton gradient. The calculation methods used here are evolving state of the art techniques and they will be tested and improved by these calculations. This project is jointly funded by the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences; the Physics of Living Systems Program in the Division of Physics, and the Chemistry of Life Processes Program in the Division of Chemistry in the Directorate of Mathematical and Physical Sciences.