Neutron Diffraction and MD Studies of the Studies of the Structure of Aqueous Sol

水溶胶结构研究中的中子衍射和MD研究

• 批准号: 7545816
• 负责人: JOHN W BRADY
• 金额: $ 29.65万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7545816
• 关键词: Achievement; Affect; Alanine; Amino Acids; Arabinose; Architecture; Binding; Biological; Characteristics; Classification; Complex; Cyclohexanes; Cyclohexanol; Cytidine Monophosphate; Data; Development; Disease; Drug Design; Environment; Galactose; Glucosamine; Glucose; Glycine; Glycols; Goals; Guanosine Monophosphate; Hexoses; Hydration status; Hydrogen; Hydrogen Bonding; Isopropanol; Label; Ligands; Liquid substance; Location; Mannose; Methanol; Methods; Modeling; Molecular; Molecular Conformation; Molecular Structure; Monosaccharides; Neutron Diffraction; Neutrons; Nucleotides; Oxygen; Pentoses; Positioning Attribute; Procedures; Proline; Property; Public Health; Research Personnel; Selenium; Series; Site; Solutions; Solvents; Structure; Sulfur; System; Techniques; Testing; Water; Work; Xylose; analog; aqueous; biological systems; functional group; improved; lyxose; molecular dynamics; new technology; nojirimycin; programs; research study; scyllo-inositol; simulation; small molecule; solute; sugar

This proposed project will be the continuation of an on-going study of the structure of aqueous solutions of complex biomolecular solutes using a combination of MD simulations and neutron diffraction with isotopic substitution (NDIS) experiments. Although neutron diffraction is the most useful experimental method for the study of liquid structure, the complexity of the total scattering from a biomolecular solution has rendered such experiments very difficult to interpret in terms of specific structural details. The NDIS method was developed to help simplify the interpretation of this scattering, but for large asymmetric solutes such as sugars, the scattering still cannot be interpreted in terms of specific details since each substituted hydrogen atom is in a different environment. The present project has overcome this problem by using sugar solutes specifically substituted at only a single position, allowing the NDIS experiment to probe the atomic structuring around just a single atom. These still complicated specific structure factors can then be compared directly to those calculated from MD simulations, as a means of determining the accuracy of the simulations, and if the representation is good, the wealth of information available from the simulations can be used to interpret the experimental data in detail. This method has in effect opened a new field of structural analysis of complex molecules in aqueous solution. The proposed extension will apply these newly-developed procedures to further studies of structuring in aqueous solutions of additional important biological molecules. A new, experimental concentration-dependent analysis will allow the intermolecular solvation structure to be extracted separately from the intramolecular structure. Additional intramolecular structuring studies will be used to analyze hydrogen-bonding in solutes and the conformations of solutes and how they are affected by solvation. In addition to a systematic analysis of the biologically-important simple monosaccharides and their analogs, the technique will be extended to studies of amino acids, nucleotides, and other small biological solutes. This work is important for public health because of the importance of aqueous solvation in all biological systems, and in determining the functioning of biomolecules. Such basic information is essential in designing drug molecules and biological ligands and in understanding both disease mechanisms and the functioning of normal biological systems.

这个拟议的项目将继续进行一项正在进行的研究 使用MD模拟和中子衍射与同位素的复杂生物分子溶质 替代（NDIS）实验。尽管中子衍射是最有用的实验方法 研究液体结构的研究，来自生物分子溶液的总散射的复杂性已引起 实验很难用特定的结构细节来解释。开发了NDIS方法 为了帮助简化这种散射的解释，但对于大型不对称溶质，例如糖， 散射仍然无法用特定细节来解释，因为每个取代的氢原子都在 不同的环境。本项目通过专门使用糖溶质克服了这一问题 仅在单个位置取代，允许NDIS实验探测原子结构 只是一个原子。然后可以将这些仍然复杂的特定结构因素直接与 根据MD模拟计算，以确定模拟的准确性，以及是否 表示是好的，模拟可用的大量信息可用于解释 实验数据详细。实际上，该方法开辟了一个新的复杂结构分析领域 水溶液中的分子。拟议的扩展程序将将这些新开发程序应用于 在其他重要生物分子的水溶液中进行结构的进一步研究。一个新的， 实验浓度依赖性分析将允许分子间溶剂化结构为 从分子内结构分开提取。其他分子内结构研究将是 用于分析溶质中的氢键和溶质的构象，以及它们如何受到 溶剂化。除了对生物学重要的简单单糖及其的系统分析外 类似物，该技术将扩展到氨基酸，核苷酸和其他小型生物学的研究 溶质。这项工作对公共卫生很重要，因为在所有人中溶剂化的重要性 生物系统，并确定生物分子的功能。这样的基本信息至关重要 设计药物分子和生物配体，并在理解疾病机制和 正常生物系统的功能。