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

Cuny City College, New York NY

Investigators

Abstract

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.