1. Quantum chemistry reveals thermodynamic principles of redox biochemistry
- Author
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Avi I. Flamholz, Sung-Jin Kim, Charles A. R. Cotton, Adrian Jinich, Arren Bar-Even, Alán Aspuru-Guzik, Benjamin Sanchez-Lengeling, Haniu Ren, and Elad Noor
- Subjects
0301 basic medicine ,Carboxylic Acids ,Design elements and principles ,Electron ,Biochemistry ,01 natural sciences ,Computational Chemistry ,Electrochemistry ,Biology (General) ,Density Functional Theory ,Primary (chemistry) ,Ecology ,Organic Compounds ,Chemistry ,Physics ,Chemical Reactions ,Enzymes ,Structure and function ,Biochemical Phenomena ,Computational Theory and Mathematics ,Modeling and Simulation ,Physical Sciences ,Thermodynamics ,Density functional theory ,Oxidoreductases ,Oxidation-Reduction ,Research Article ,QH301-705.5 ,010402 general chemistry ,Quantum chemistry ,Redox ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Oxidation ,Genetics ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Quantum Mechanics ,Organic Chemistry ,Chemical Compounds ,Biology and Life Sciences ,Proteins ,Quantum Chemistry ,NAD ,0104 chemical sciences ,030104 developmental biology ,Models, Chemical ,Linear Models ,Enzymology ,Acids ,NADP ,Oxidation-Reduction Reactions - Abstract
Thermodynamics dictates the structure and function of metabolism. Redox reactions drive cellular energy and material flow. Hence, accurately quantifying the thermodynamics of redox reactions should reveal design principles that shape cellular metabolism. However, only few redox potentials have been measured, and mostly with inconsistent experimental setups. Here, we develop a quantum chemistry approach to calculate redox potentials of biochemical reactions and demonstrate our method predicts experimentally measured potentials with unparalleled accuracy. We then calculate the potentials of all redox pairs that can be generated from biochemically relevant compounds and highlight fundamental trends in redox biochemistry. We further address the question of why NAD/NADP are used as primary electron carriers, demonstrating how their physiological potential range fits the reactions of central metabolism and minimizes the concentration of reactive carbonyls. The use of quantum chemistry can revolutionize our understanding of biochemical phenomena by enabling fast and accurate calculation of thermodynamic values., PLoS Computational Biology, 14 (10), ISSN:1553-734X, ISSN:1553-7358
- Published
- 2018
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