OPTICAL PROPERTIES OF BIOLOGICAL MACROMOLECULES

生物大分子的光学性质

• 批准号: 3271447
• 负责人: ROBERT W WOODY
• 金额: $ 18.84万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-12-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3271447
• 关键词: chemical group; chemical structure function; chromophore; circular dichroism; conformation; electronic spectra; heme; hemoprotein; infrared spectrometry; macromolecule; mathematical model; mathematics; molecular dynamics; molecular energy level; nuclear magnetic resonance spectroscopy; nucleic acid structure; photosynthetic bacteria; physical model; protein structure function; site directed mutagenesis

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.

该项目的目标是扩展光学的应用 光谱学，特别是圆二色性（CD），在研究中 大分子结构和功能。一般的做法是结合 可行的实验和理论方法，并研究两者 模型系统和具有直接生物学意义的系统。在接下来的时间里 五年内将研究三个主要领域：（1）内在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CD。目前计算多肽的模型 CD将被细化。改进后的模型将应用于 beta 回合和 β折叠和无序肽。 α螺旋和 超二级结构中的 α 螺旋和 β 折叠之间将是 经过考虑的。最终效应影响规模的程度 α-螺旋 CD 谱将通过短的研究进行实验评估 旨在增强α螺旋稳定性的肽。将军 计算蛋白质中侧链 CD 贡献的程序将是 开发的，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 已知具有异常远紫外线CD。计算也将 对牛胰腺胰蛋白酶抑制剂进行了一系列的研究 定点突变取代了芳香族基团或二硫化物。这 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 模拟相结合进行研究 蛋白质。原肌球蛋白中的四个酪氨酰残基簇也将被 通过 MD 建模，计算侧链 CD 贡献。这 各种血红素蛋白的血红素平面性偏差的作用 将探讨确定CD。定点突变的影响 在光合细菌的反应中心将研究两者 实验和理论上。晶体场对电荷的影响 将计算碱基的分布和电子光谱。这 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 计算溶液中的寡核苷酸，包括吸收 和CD。