OPTICAL PROPERTIES OF BIOLOGICAL MACROMOLECULES

该项目的总体目标是改进 分析和拓宽光谱学的应用，特别是 圆二色性（CD），用于蛋白质和核酸的研究。 近年来，人们对裁谈会的兴趣又有了很大的恢复 由于其在监测蛋白质折叠方面的价值， 蛋白质的结构分析，突变蛋白的特征， 在DNA和RNA的构象转变之后， 蛋白质-蛋白质和蛋白质-核酸平衡和动力学。 期间 未来五年，该项目将集中在四个主要领域：（1） 蛋白质的内在CD，即主链和侧链贡献;（2） 由于蛋白质-配体相互作用，蛋白质的外源性CD;（3） 电子结构的核酸碱基和CD的 寡核苷酸;（4）参与蛋白质的实验研究 转录及其调控。 在第一个领域， 用于计算多肽CD的理论模型为 扩展到包括高能量转换，静态场效应， 肽间电荷转移 DeVoe的扩展版本或 经典的极化率模型将得到更广泛的应用， 更令人满意的带状物。 捐款的计算 具体的芳族侧链将进行和结果比较 与定点突变的结果相比。 CD-分子动力学组合 (MD)计算将在模型多肽和小分子多肽上进行。 proteins. 对于第二个区域，血红素跃迁的CD 将计算高分辨率X射线衍生结构的许多 蛋白质，以及碳单氧肌红蛋白血红素异构体的MD轨迹。 我们在解释静态场对电子结构的影响方面的工作 将延伸到核苷酸和碱基对。 此外，其NMR结构已被确定的寡核苷酸的CD也被确定。 将计算并与实验进行比较。 的 真核生物大亚基C端结构域的构象 RNA聚合酶II，它由一个重复的长序列组成， 七肽，将进行研究。 人I型Tax蛋白 白血病病毒及其与碱性亮氨酸拉链蛋白的相互作用， 以及碱性螺旋-环-螺旋蛋白，将通过CD进行研究， 荧光。

The overall objective of this project is to improve the methods of analysis and broaden the applications of optical spectroscopy, especially circular dichroism (CD), to the study of proteins and nucleic acids. There has been a major resurgence of interest in CD in recent years because of its value in monitoring protein folding, in secondary structural analysis of proteins, in characterizing mutant proteins, in following conformational transitions in DNA and RNA, and in measuring protein-protein and protein-nucleic acid equilibria and kinetics. During the next five years, the project will concentrate on four major areas: (1) intrinsic CD of proteins, i.e. backbone and side-chain contributions; (2) extrinsic CD of proteins due to protein-ligand interactions; (3) electronic structure of the nucleic acid bases and the CD of oligonucleotides; (4) experimental studies of proteins involved in transcription and its regulation. In the first area, the basic theoretical model used in calculating the CD of polypeptides will be extended to include high-energy transitions, static-field effects, and interpeptide charge transfer. The extended version of the DeVoe or classical polarizability model will be applied more extensively to provide more satisfactory band shapes. Calculations of the contributions of specific aromatic side chains will be performed and the results compared to those from site-directed mutagenesis. Combined CD-molecular dynamics (MD) calculations will be performed on model polypeptides and small proteins. With respect to the second area, the CD of heme transitions will be calculated for high-resolution X-ray-derived structures of many proteins, and for MD trajectories for carbonmonoxymyoglobin heme isomers. Our work on interpreting static-field effects on the electronic structure of the nucleic acid bases will be extended to nucleotides and base pairs. In addition, the CD of oligonucleotides for which NMR structures have been determined will be calculated and compared with experiment. The conformation of the C-terminal domain of the large subunit of eukaryotic RNA polymerase II, which consists of a long sequence of a repeating heptapeptides, will be investigated. The Tax protein of human type I leukemia virus and its interactions with basic-leucine zipper proteins, as well as basic helix-loop-helix proteins, will be studied by CD and fluorescence.