Experimental Studies of Water Structuring by Sugars

糖水结构的实验研究

• 批准号: 6621534
• 负责人: JOHN W BRADY
• 金额: $ 25.13万
• 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 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6621534
• 关键词: carbohydrates; chemical structure function; chemical synthesis; chromatography; computer simulation; crystallization; hexoses; intermolecular interaction; mathematics; model design /development; molecular dynamics; molecular shape; molecular site; neutron diffraction; pentoses; physical model; radiotracer; stereoisomer; structural biology; water; water solution

DESCRIPTION (provided by applicant): Computer simulations have proven to be very useful for the study of the structuring of complex solutions, providing information difficult or impossible to obtain by experimental means. 'While this level of detail is one of the great advantages of Molecular Mechanics (MM) calculations, there is an obvious and growing necessity to validate the results of such simulations by a demanding comparison with experiment. The objective of the studies proposed here will be to use MM simulations to model the solvent structuring imposed on water by complex biological solutes, and then for comparison, to measure this structuring for the same molecules using first difference isotopic substitution neutron diffraction experiments. The molecules to be studied will be various pentose and hexose sugars, because of their practical experimental advantages over the peptides, their overall biological importance, and their usefulness as more general models for biopolymer hydration. The sugar molecules to be studied will be prepared synthetically, with only single and double isotopic substitutions at specific positions, in order to eliminate the loss in detail due to averaging over different environments when using multiply-labeled solutes. The collective structure which solutes impose upon solvent water plays a profound role in many biological processes, such as protein folding, membrane formation, and the binding of ligands to proteins. Such structuring is often invoked to explain all manners of phenomena, but without any definitive way to actually probe this structure or specify its detailed relationship to the solute topology. Molecular Dynamics simulations offer an ideal way to study this structuring on the molecular level, but in general there have been few ways to compare the calculated results with experiment. The principal experimental technique for probing liquid structure is neutron diffraction, which has been very successful in determining the structures of electrolyte solutions and solutions of simple solutes such as rare gases. Unfortunately, the averaging over all like atoms obscures anisotropic structuring details in more complex solutes. The proposed project will use synthetic methods to prepare sugar molecules singly substituted with deuterium or 13C at specific positions, and double substitutions with one atom each of D and 13C, exploiting the overlapping rdfs to probe the anisotropy in the solvent distribution. The radial distribution function for these individual atoms will then be compared with those calculated from new MD simulations of these sugars at the same high experimental concentrations.

描述（由申请人提供）：计算机模拟已被证明是 非常有用的研究结构的复杂的解决方案，提供 通过实验手段难以或不可能获得的信息。'While 这种层次的细节是分子力学（MM）的最大优点之一 计算，有一个明显的和日益增长的必要性，以验证结果 通过与实验进行严格的比较来分析这种模拟。的目标 这里提出的研究将使用MM模拟来模拟溶剂 结构强加于水的复杂的生物溶质，然后为 为了测量相同分子的这种结构，首先使用 同位素替代中子衍射实验。的分子 要研究的将是各种戊糖和己糖，因为它们的 肽的实际实验优势，它们的整体生物学特性 重要性以及它们作为生物聚合物更一般模型的有用性 水合作用待研究的糖分子将通过合成制备， 仅在特定位置具有单和双同位素取代， 为了消除由于对不同的平均而造成的细节损失， 当使用多标记溶质时， 溶质强加于溶剂水的集体结构起着 在许多生物过程中，如蛋白质折叠，膜 形成以及配体与蛋白质的结合。这种结构往往 它被用来解释各种现象，但没有任何明确的方法来解释。 实际上探测这个结构或指定它的详细关系， 溶质拓扑分子动力学模拟为研究 这种结构在分子水平上，但在一般情况下， 计算结果与实验结果比较的方法。校长 探测液体结构的实验技术是中子衍射， 在确定电解质结构方面非常成功 溶液和简单溶质的溶液，如稀有气体。不幸的是， 在所有相似原子上的平均模糊了各向异性结构细节 更复杂的溶质。拟议的项目将使用合成方法， 制备在特定位置被氘或13 C单取代的糖分子 位置，并用D和13C中的每个原子进行双取代， 重叠的RDF以探测溶剂分布中的各向异性。的 然后将比较这些单个原子的径向分布函数 与从这些糖的新MD模拟计算出的那些在相同的高 实验浓度