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: 7195451
• 负责人: JOHN W BRADY
• 金额: $ 29.55万
• 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/7195451
• 关键词: Achievement; Affect; Alanine; Amino Acids; Arabinose; Architecture; Binding; Biological; Characteristics; Class; Classification; Complex; Cyclohexane; Cyclohexanes; Cyclohexanol; Cytidine Monophosphate; Data; Development; Disease; Drug Design; Environment; Galactose; Glucosamine; Glucose; Glycine; Glycol; 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; Range; Research Personnel; Selenium; Series; Site; Solutions; Solvents; Structure; Sulfur; System; Techniques; Testing; Water; Work; Xylose; analog; aqueous; functional group; improved; lyxose; molecular dynamics; new technology; nojirimycin; programs; research study; scyllo-inositol; simulation; small molecule; solute; sugar

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：该提出的项目将继续进行一项正在进行的研究，对复杂生物分子溶质水溶液的结构进行了使用MD模拟的结合以及与同位素替代（NDIS）实验的中子衍射的组合。尽管中子衍射是研究液体结构的最有用的实验方法，但生物分子溶液的总散射的复杂性使此类实验非常难以解释，从特定的结构细节来看。开发了NDIS方法是为了帮助简化这种散射的解释，但是对于大型不对称溶质（例如糖），由于每个取代的氢原子都在不同的环境中，因此仍无法用特定细节来解释散射。本项目通过使用仅在单个位置上专门取代的糖溶质克服了这一问题，从而使NDIS实验仅在一个原子附近探测原子结构。然后可以将这些仍然复杂的特定结构因子直接与从MD模拟中计算出的那些，以确定模拟的准确性，如果表示形式良好，则可以使用模拟中可获得的大量信息来详细解释实验数据。实际上，该方法为水溶液中复杂分子的结构分析打开了新的领域。拟议的扩展将应用这些新开发的程序，以进一步研究其他重要生物分子的水溶液中的结构。一个新的实验浓度依赖性分析将使分子间溶剂化结构与分子内结构分开提取。其他分子内结构研究将用于分析溶质中的氢键，溶质的构象以及它们如何受溶剂的影响。除了对生物学上重要的简单单糖及其类似物的系统分析外，该技术还将扩展到氨基酸，核苷酸和其他小型生物溶质的研究。这项工作对公共卫生很重要，因为在所有生物系统中水溶液的重要性以及确定生物分子的功能。这种基本信息对于设计药物分子和生物配体以及理解疾病机制和正常生物系统的功能至关重要。