OPTICAL PROPERTIES OF BIOLOGICAL MACROMOLECULES

本项目的目标是扩大光学技术的应用范围 光谱学，特别是圆二色谱(CD)在研究中的应用 大分子结构和功能。通常的方法是将 只要可行，就用实验和理论的方法，并研究两者 模型系统和具有直接生物意义的系统。在下一次 五年内将主要研究三个方面：(1)本征态Cd 蛋白质，研究主链和侧链的贡献；(2) 发色基团和辅酶的外在Cd贡献； (3)核酸的CD。多肽计算的现行模型 CD将得到提炼。改进后的模型将应用于贝塔转弯和 Betasheet和无序肽。α螺旋和α螺旋之间的相互作用 在超二级结构中的阿尔法螺旋和贝塔薄片之间 考虑过了。末端效应影响的程度 阿尔法-螺旋CD光谱将通过短的研究进行实验评估 旨在增强α-螺旋稳定性的多肽。一位将军 计算蛋白质中侧链CD贡献的程序将是 已开发，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，这些蛋白质是 已知有异常的远紫外线CD。计算也将是 进行了牛胰蛋白酶抑制剂，其中一系列的 定点突变已经取代了芳香基团或二硫化物。这个 蛋白质动力学对侧链和主干CD的影响将是 通过将CD计算与MD模拟相结合对Small进行研究 蛋白质。原肌球蛋白中四个酪氨酰残基的簇也将 由MD模拟，并计算侧链CD的贡献。这个 不同血红素蛋白在血红素平面偏离中的作用 将探索确定CD。定点突变的影响 在光合作用细菌的反应中心将被研究 从实验和理论上都是如此。晶场对电荷的影响 将计算碱基的分布和电子光谱。这个 然后，计算将扩展到核苷、核苷酸和 寡核苷酸。为晶体开发的方法将被应用 对溶液中寡核苷酸的计算，包括两种吸收 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.