Theoretical Investigations of some Outstanding Problems in Biophysical Chemistry

生物物理化学若干突出问题的理论研究

• 批准号: RGPIN-2022-04842
• 负责人: Matta, Cherif
• 金额: $ 2.62万
• 依托单位: Mount Saint Vincent University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=748561
• 关键词: Theoretical; Investigations; some; Outstanding; Problems

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.

线粒体负责食品中大多数能量的转化为卓越代谢燃料，即ATP（腺苷5'-三磷酸）。各种代谢产物最终在线粒体基质内氧化，它们被氧化，以通过“电子传输链”（ETC）在线粒体内膜内（IMM）内传递电子。从ETC的反应中释放的能量用于在线粒体间间隙中泵送质子，从而产生和维持化学和电势梯度。质子通过ATP合酶的通道向下下坡，通过将第三个磷酸组添加到ADP形成ATP来释放ATP合酶捕获的能量。我们最近发现，每次选择质子通过其通道时，ATP合酶必须耗散最小能量（> kbtln2）。这被称为“ Landauer的原则”。我们还发现，从5种不同物种中分离出来的酶具有一致的电性能。例如，该蛋白质的固有静电电势会导致质子的入口点（在间隙侧）与其出口点（在基质侧）之间产生势差。由于质子梯度，该电压加强了一个电压，并贡献了一个具有相同数量级的能量术语，但符号相反，因此，可以说，该酶已经演变为为自己的操作付费。该提案将在更大的深度探讨这些最近但初步的发现。使用量子化学，我们还将研究越过IMM的强电场如何影响ETC反应的热力学和动力学。感兴趣的一个特殊反应是活性氧的产生。我们提出了一种控制IMM潜力的反馈机制，该系统可以使系统反应“ Le Chatelier”以维持体内平衡。第二条研究将调查热力学作为（达尔文）自然选择核酸的益生元驱动因素的可能作用。具体来说，我们希望了解为什么我们今天拥有的核酸以当今的特定形式而不是在任何紧密相关且可访问的替代形式中？这是自由能的问题还是还有其他因素？最后，我们对与生命起源有关的问题的兴趣使我们遇到了世纪以来的弥漫性星际乐队（DIBS）的问题。由于许多恒星的视线沿线乌尘云，这些线条遭受了线条。我们最近的工作已经确定了4个新型相关DIB系（4个家族）的组，每个组可能源于独特的化学源（分子，复杂离子，原子簇，...）。统计数据和最先进的频谱计算的结合将阐明这些新DIB家族的可能化学来源。