OPTICAL PROPERTIES OF BIOLOGICAL MACROMOLECULES

本项目的目标是扩展光学的应用 光谱，特别是圆二色性（CD），在研究 大分子结构与功能一般的方法是将联合收割机 实验和理论方法，只要可行，并研究两者 模型系统和具有直接生物学意义的系统。在下一个 五年内将研究三个主要领域：（1）内在的CD 蛋白质，研究主链和侧链的贡献;（2） 发色辅基和辅酶的外在CD贡献; (3)核酸的CD。目前计算多肽的模型 CD将被改进。改进后的模型将被应用于β转弯， β片和无序肽。α螺旋之间的相互作用， 在超二级结构中的α螺旋和β折叠之间， 考虑了最终效应影响的程度 α-螺旋CD光谱将通过短的 被设计为具有增强的α-螺旋稳定性的肽。一般 计算蛋白质中侧链CD贡献的程序将是 开发，包括三个芳香族侧链，组氨酸和 二硫化物该程序将应用于一系列蛋白质， 已知有异常远紫外CD计算还将 进行牛胰蛋白酶抑制剂，其中一系列的 定点突变取代了芳族基团或二硫化物。的 蛋白质动力学对侧链和主链CD的影响将是 通过将CD计算与MD模拟相结合，对小 proteins.原肌球蛋白中的一簇四个酪氨酰残基也将被 通过MD建模，并计算侧链CD贡献。的 不同血红素蛋白质血红素平面性偏离的作用 将探讨如何确定裁谈会。定点突变的影响 在光合细菌的反应中心， 实验和理论上。电荷的晶场效应 计算了碱的分布和电子光谱。的 计算将扩展到核苷，核苷酸和 寡核苷酸将应用为晶体开发的方法 溶液中寡核苷酸的计算，包括吸收 和CD。

The objective of this project is to extend the applications of optical spectroscopy, especially circular dichroism (CD), in the study of macromolecular structure and function. The general approach is to combine experimental and theoretical methods wherever practical, and to study both model systems and systems of direct biological interest. During the next five years three major areas will be studied: (1) the intrinsic CD of proteins, with studies of both backbone and sidechain contributions; (2) extrinsic CD contributions of chromophoric prosthetic groups and coenzymes; (3) the CD of nucleic acids. The current model for calculating polypeptide CD will be refined. The improved model will be applied to beta-turns and betasheets, and unordered peptides. Interactions among alpha helices and between alpha helices and beta-sheets in supersecondary structures will be considered. The extent to which end effects influence the magnitude of the alpha-helix CD spectrum will be assessed experimentally by studies of short peptides designed to have enhanced alpha-helical stability. A general program to calculate side-chain CD contributions in proteins will be developed, including the three aromatic side chains, histidine and disulfides. This program will be applied to a series of proteins which are known to have anomalous far ultraviolet CD. Calculations will also be performed for bovine pancreatic trypsin inhibitor, in which a series of site-directed mutations have replaced aromatic groups or disulfides. The effects of protein dynamics on sidechain and backbone CD will be investigated by combining CD calculations with MD simulations on small proteins. A cluster of four tyrosyl residues in tropomyosin will also be modeled by MD and the side-chain CD contributions will be calculated. The role of deviations from planarity in the heme of various heme proteins in determining the CD will be explored. The effects of site-directed mutations in the reaction center of a photosynthetic bacterium will be studied both experimentally and theoretically. Crystal field effects on the charge distribution and electronic spectra of the bases will be calculated. The calculations will then be extended to nucleosides, nucleotides and oligonucleotides. The methods developed for the crystals will be applied to calculations on oligonucleotides in solution, including both absorption and CD.