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Free Energy Simulations of Complex Biological Systems at Constant PH

出版	University of Florida, 2013
URL	http://books.google.com.hk/books?id=ITB5AQAACAAJ&hl=&source=gbs_api

註釋Solution pH has profound effects on the structure, function, and activity of many complex biomolecules that catalyze the chemical reactions responsible for sustaining life. Even focusing on the human body, the various physiological environments span a wide pH range--as low as 1 in the stomach to values as high as 8.1 in pancreatic secretions. Small changes from the normal pH of a biomolecule's environment can be catastrophically disruptive to its activity. For example, a change in pH of as little as 0.1 pH units in the human bloodstream is enough to cause life-threatening alkalosis or acidosis. Due to the importance of pH in biology and the profound effect it can have on biomolecules, it is important to incorporate pH effects in computational models designed to treat these biomolecules. The solution pH controls protonation state equilibria of specific functional groups prevalent in biomolecules, such as carboxylates, amines, and imidazoles. These protonation states in turn affect the charge distribution in the biomolecule which can have a significant impact on both its 3-dimensional structure as well as interactions with the surrounding environment. In many cases, pH can also impact whether or not a proton donor or acceptor will be available for catalysis during the course of the biocatalytic mechanism. The aim of my work is to develop accurate and efficient computational models to probe the pH-dependent behavior of proteins and nucleic acids. The models must be carefully designed to obey the laws of thermodynamics under the constraint of an externally applied pH. Only then can the results be directly compared to experimental measurements.