SOLVENT EFFECTS ON BIOMOLECULAR STRUCTURE AND PROCESS

我们在此请求继续支持理论和 生物分子体系的计算研究 分子模拟程序，即蒙特卡罗(MC)和 分子动力学(MD)计算。以前项目中的研究 这些时期涉及到水和水的基本问题。 与生物分子体系相关的溶液结构，以及 蛋白质和核酸成分的水合作用。重点在 建议的项目期将放在结构和 寡核苷酸双链及其相关分子的动力学 晶体水合物和溶液中的络合物。在这些系统中， 溶剂效应(水合和离子气氛)是众所周知的 具有至关重要的意义，但它们的可操作性还不是 理论上理解不充分的或完全解释的 计算。随着现在这一代超级计算机的出现， 所连接的处理器和图形工作站具有 严格而广泛地处理系统的分子模拟 包括溶剂效应所需的维度 生物分子现在已经最小限度地实现了，而计算机 能力发展迅速。主要的理论和 分子模拟的计算方法是可用的 在NSFnet中或通过NSFnet可从该实验室访问。建议数 研究建立在最近的力场发展和进展的基础上 方法学，特别是新的和新的分析程序 利用分子图形学对DNA的MD结果进行推广 及时进行理论研究和具体应用 分子模拟在核酸研究领域的应用。 建议的项目包括进一步的确定和分析 寡核苷酸的水化密度分布和 DNA的正则形式、自由能的模拟研究 反离子分布作为函数的B跃迁和MC研究 盐和介电效应，一种新的MD图形分析 以一套完整的构象， 螺旋面和结点参数，一种形态分类 在此基础上，MD研究了寡核苷酸晶体结构数据 对dCpG/前列腺素晶体水合物的表征研究 核酸力场和静电模型，规程 对于使用有约束的MD和MC Boltzmann跳跃方法 用于确定溶液结构的NOESY距离信息 与DNA修复有关的完整和受损序列，以及 水化、加盐和侧翼顺序对水合作用影响的研究 含有GAATTC蛋白结合位点的12聚体

We request herein continuation support for theoretical and computational studies on systems of biological molecules using molecular simulation procedures, i.e., Monte Carlo (MC) and molecular dynamics (MD) calculations. Studies in previous project periods have dealt with fundamental issues in water and aqueous solution structure relevant to biomolecular systems, and the hydration of protein and nucleic acid constituents. Emphasis in the proposed project period will be placed on the structure and dynamics of oligonucleotide duplexes and related molecular complexes in crystal hydrates and in solution. In these systems, solvent effects (hydration and ion atmosphere) are well known to be of crucial significance, but their operative nature is not yet well understood nor fully accounted for by theoretical calculations. With the present generation of supercomputers, attached processors and graphic workstations, the capability of molecular simulation to treat rigorously and extensively systems of the dimensionality required for including solvent effects with biological molecules has now been minimally achieved, and computer capabilities are developing rapidly. The principal theoretical and computational methodologies for molecular simulation are available in or accessible via NSFnet from this laboratory. The proposed studies build upon recent force field developments, advances in methodology and particularly new and novel procedures for analysis of MD results on DNA using molecular graphics to carry forward timely theoretical investigations and specific applications of molecular simulation in the area of nucleic acids research. Proposed projects include the further determination and analysis of hydration density distributions in oligonucleotides and canonical forms of DNA, free energy simulation studies of the A to B transition, MC studies of counterion distributions as a function of salt and dielectric effects, a new graphical analysis of MD calculations on DNA in terms of a complete set of conformational, helicoidal and junction parameters, a morphological classification of oligonucleotide crystal structure data on this basis, MD studies of the dCpG/proflavin crystal hydrate, characterization studies of nucleic acid force fields and electrostatic modelling, protocols for use of restrained MD and MC Boltzmann jump methods with 20- NOESY distance information for determination of solution structure of intact and damaged sequences implicated in DNA repair, and a study of the effects of hydration, salt and flanking sequence on a 12-mer containing the GAATTC protein binding site