Theoretical Investigations of some Outstanding Problems in Biophysical Chemistry

点击翻译按钮获取中文摘要

The mitochondrion is responsible for the conversion of most of the energy in the foodstuff to the universal metabolic fuel par excellence, ATP (adenosine 5'-triphosphate). Various metabolites eventually make their way inside the mitochondrial matrix where they are oxidized delivering electrons to be channeled through the "electron transport chain" (ETC) inside the inner mitochondrial membrane (IMM). The energy released from the reactions of the ETC is used to pump protons in the mitochondrial inter-membrane gap creating and maintaining a chemical and an electrical potential gradient. Protons going back downhill, through ATP synthase's channel, release this energy which is captured by ATP synthase by adding a third phosphate group to ADP to form ATP. We have recently discovered that ATP synthase must dissipate a minimum energy (> kBTln2) every time it selects a proton to go through its channel. This is called "Landauer's principle". We have also found that the enzyme, isolated from 5 different species, have consistent electrical properties. For example, the protein's intrinsic electrostatic potential gives rise to a potential difference between the entry point of the protons (on the gap side) and their exit point (on the matrix side). This voltage reinforce one due to the proton gradient and contribute an energy term that is of the same order of magnitude but opposite in sign to that which needs to be dissipated. Hence, the enzyme has evolved to pay for its own operation, so to speak. This proposal will explore these recent but preliminary findings in much greater depth. Using quantum chemistry, we will also study how the strong electric field that crosses the IMM influences the thermodynamics and kinetics of the ETC reactions. One particular reaction of interest is that of the generation of reactive oxygen species. We propose a feedback mechanism of control of the IMM potential whereby the system reacts à la "Le Chatelier's" to maintain homeostasis. A second line of research will inquire into the possible role of thermodynamics as a prebiotic driver of (Darwinian) natural selection of nucleic acids. Specifically, we wish to understand why the nucleic acids we have today are in the present-day particular form and not in any of the closely related and accessible alternative forms? Is it a matter of free energy or are there other factors? Finally, our interest in questions related to origins of life led us to the century-old problem of Diffuse Interstellar Bands (DIBs). These are absorption lines due to dust clouds along the sight-lines of many stars. Our recent work has identified 4 novel groups of related DIB lines (4 families), each of which may well originate from a unique chemical source (a molecule, a complex ion, an atomic cluster, ...). A combination of statistics and state-of-the-art ab initio spectral calculations will shed light on possible chemical sources of these new DIB families.