Theoretical Studies of the Circular Dichroism of Peptides and Proteins

9632124 Hirst这项研究将为给定蛋白质结构的圆二色性（CD）的计算提供理论基础。 CD基本上是一种电子分子性质，因此这项工作的第一部分涉及应用最先进的量子化学方法来表征蛋白质中的各种发色团。 一旦对这些基团进行建模，将使用半经验矩阵方法计算蛋白质的CD。 赫斯特博士将使用开发的方法来研究对螺旋CD的影响。 他将与德克萨斯A M大学的Jeffery Kelly教授合作研究β-折叠肽模拟物的CD。 CD计算和MD模拟（来自斯克里普斯研究所的Charles布鲁克斯教授）将用于模拟蛋白质折叠过程中CD的时间演变。 圆二色性（CD）光谱是一种广泛使用的蛋白质结构探针，从早期的实验，以确定手性的β-螺旋到最近的皮秒时间分辨CD测量的一氧化碳从肌红蛋白的解离。 圆二色谱是研究蛋白质折叠的结构、热力学和动力学的常规方法。 蛋白质CD的许多理论基础已经建立，但CD与蛋白质详细结构之间的关系尚未完全理解。 这项研究的结果，从模拟计算肽和蛋白质的圆二色光谱的理论方法的发展，将提供蛋白质的原子详细结构和它们的CD之间的联系。 ***

9632124 Hirst This research will provide the theoretical underpinning for the calculation of the circular dichroism (CD) of a protein given its structure. CD is fundamentally an electronic molecular property, and so the first component of the work involves the application of state-of-the-art quantum chemistry methods to characterize the various chromophoric groups in proteins. Once these groups have been modeled, the semi-empirical matrix method for calculating the CD of proteins will be used. Dr. Hirst will use the developed methods to investigate the influences on the CD of helices. In collaboration with Professor Jeffery Kelly at Texas A & M he will investigate the CD of (-sheet peptidomimetics. CD calculations and MD simulations (from Professor Charles Brooks at The Scripps Research Institute) will be used to model the time-evolution of CD during protein folding. %%% Circular dichroism (CD) spectroscopy is a widely used probe of protein structure from early experiments to determine the handedness of (-helices to recent picosecond time-resolved CD measurements of the dissociation of carbonmonoxide from myoglobin. CD is routinely employed to study the structure, the thermodynamics and the kinetics of protein folding. Much of the theoretical basis of the CD of proteins has been established, but the relationship between CD and the detailed structure of proteins has yet to be fully understood. The results of this research, the development of theoretical methods to calculate the circular dichroism spectra of peptides and proteins from simulations, will provide the connection between the atomic-detailed structure of proteins and their CD. ***