NUCLEIC ACID ELECTROSTATIC PROPERTIES FROM CRYSTALS

晶体核酸的静电特性

• 批准号: 2179872
• 负责人: BRYAN M CRAVEN
• 金额: $ 17.13万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2179872
• 关键词: X ray crystallography; adduct; adenosine; chemical models; computer program /software; crystallization; cytidine; dinucleotide; drug interactions; electron density; guanosine; ionic bond; mathematical model; neutron diffraction; nucleic acid structure; oligonucleotides; physical model

Electrostatic properties of the nucleic acids will be determined from X- ray and neutron single crystal diffraction studies of simple nucleic acid components ranging up to minihelical dinucleotide structures. Emphasis will be on mapping the electrostatic potential, either within the crystal unit cell, or for molecules extracted from the crystal lattice. We have shown that the electrostatic potential can he experimentally determined more easily than other molecular properties such as the charge density or the electric field. With a simple structure model including only two atomic charge parameters in addition to the atomic parameters used in conventional crystal structure determinations, we expect to obtain physically meaningful maps of electrostatic potential for molecules containing at least 50 atoms. Such results will be of particular significance for the nucleic acids which have strongly ionic character and contain many polar groups. The H bonding of the bases, their stacking, the binding of counterions and polar molecules such as water, all involve interactions which are predominantly electrostatic. We will map the electrostatic potential in the voids of nucleotide crystal structures after water molecules, cations and intercalated drugs are completely or selectively removed from the pseudoatom model, and in this way we will study their binding sites. An important characteristic of this project is that experimental electrostatic potentials will be carefully cross-checked for consistency with each other and with results from simple benchmark crystal structures. We outline a new procedure for representing the electron density, the modulus of the electric field, or the electrostatic potential as the sum of contributions from spherically symmetric atomic charges. Our procedure overcomes the disadvantages inherent in fitting procedures that are based on the points of a grid and occur within a finite volume in space. The aim is to compile a database of atomic charges which can be conveniently incorporated as part of a standardized force field for molecular mechanics and molecular dynamics calculations.

核酸的静电性能将从X-确定 射线和中子单晶体衍射研究简单核酸 成分到迷你二核苷酸结构。强调 将在晶体内映射静电电势 单位细胞，或从晶格中提取的分子。我们有 表明他可以实验确定静电电位 比其他分子特性（例如电荷密度或 电场。使用一个简单的结构模型包括两个 原子电荷参数除了使用的原子参数 常规的晶体结构确定，我们希望获得 分子的物理有意义的静电潜力图 至少包含50个原子。 这种结果对于核酸特别重要 具有强烈的离子特性，并且包含许多极性群体。 h 基地的粘结，它们的堆叠，柜台和极地的结合 分子（例如水）都涉及主要是相互作用的 静电。我们将在空隙中绘制静电电势 水分子，阳离子和核苷酸晶体结构 插量的药物是完全或有选择地从 假子模型，通过这种方式，我们将研究其结合位点。 该项目的一个重要特征是实验 静电电势将仔细检查以保持一致性 彼此之间以及简单基准晶体结构的结果。 我们概述了代表电子密度的新程序， 电场的模量或静电电势作为总和 球形对称原子电荷的贡献。我们的程序 克服基于拟合程序固有的缺点 在网格的点上，出现在空间有限体积内。目的 是要编译一个可以方便的原子电荷数据库 作为分子力学的标准力场的一部分合并 和分子动力学计算。