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

这项拟议的项目将是对水溶液结构正在进行的研究的继续 分子动力学模拟和中子衍射与同位素相结合的复杂生物分子溶质 替代(NDIS)实验。尽管中子衍射法是最有用的实验方法 对液体结构的研究，生物分子溶液总散射的复杂性使得 这些实验很难用具体的结构细节来解释。开发了NDIS方法 为了帮助简化对这种散射的解释，但对于大的不对称溶质，如糖， 散射仍然不能用具体细节来解释，因为每个被取代的氢原子都在一个 不同的环境。本项目通过专门使用糖溶质克服了这一问题 只在一个位置被替换，允许NDIS实验探测周围的原子结构 只有一个原子。然后，这些仍然复杂的特定结构因素可以直接与 从MD模拟计算，作为确定模拟准确性的一种手段，如果 代表性很好，从模拟中获得的丰富信息可以用来解释 详细的实验数据。该方法实际上开辟了复杂结构分析的新领域。 水溶液中的分子。拟议的延期将把这些新开发的程序应用于 进一步研究其他重要生物分子在水溶液中的结构。一种新的， 实验浓度相关分析将允许分子间溶剂化结构为 从分子结构中分离出来。其他的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是如何受 溶剂化。除了系统分析具有生物重要性的简单单糖及其 类似的，这项技术将扩展到氨基酸、核苷酸和其他小型生物的研究 溶质。这项工作对公众健康很重要，因为水溶液溶剂化的重要性 生物系统，以及确定生物分子的功能。这些基本信息在 设计药物分子和生物配体，并了解疾病机制和 正常生物系统的运作。

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.