SOLVENT EFFECTS ON BIOMOLECULAR STRUCTURE AND PROCESS

我们在此请求继续支持理论和 生物分子系统的计算研究， 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 期间处理了水和水的基本问题 与生物分子系统相关的溶液结构， 蛋白质和核酸成分水合作用。 重点 建议的项目周期将放在结构上， 寡核苷酸双链体和相关分子的动力学 晶体水合物和溶液中的络合物。 在这些系统中， 溶剂效应（水合作用和离子气氛）是众所周知的， 具有至关重要的意义，但其操作性质尚未确定。 很好地理解，也没有完全解释的理论 计算。 有了这一代的超级计算机， 连接的处理器和图形工作站， 分子模拟，以严格和广泛地处理系统 包括溶剂效应所需的维数， 生物分子已经最低限度地实现了，计算机 能力正在迅速发展。 主要的理论和 分子模拟的计算方法是可用的 在或通过NSFnet从本实验室访问。 拟议 研究建立在最近的力场发展，进展， 方法，特别是新的和新颖的分析程序 使用分子图形对DNA的MD结果进行结转 及时的理论研究和具体应用 在核酸研究领域的分子模拟。 建议的项目包括进一步确定和分析 寡核苷酸中的水合密度分布， DNA的典型形式，自由能模拟研究的A， B跃迁，MC研究作为函数的逆态分布 盐和介电效应，一个新的图形分析MD 用一套完整的构象， 螺旋面和结参数，形态分类 在此基础上，对寡核苷酸的晶体结构数据进行MD研究 的dCpG/原黄素晶体水合物，表征研究 核酸力场和静电建模，协议 对于使用限制MD和MC玻尔兹曼跳跃方法， 用于确定溶液结构的NOESY距离信息 完整和受损的DNA修复序列， 研究了水化、盐和侧翼序列对 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