Experimental Studies of Water Structuring by Sugars

糖水结构的实验研究

• 批准号: 6880083
• 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 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6880083
• 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（申请人提供）：已证明计算机模拟是 对于研究复杂解决方案的结构非常有用，提供 信息难以通过实验手段获得。 '尽管 这种细节是分子力学（MM）的最大优势之一 计算，验证结果有一个明显且越来越多的必要性 通过与实验进行苛刻的比较来模拟。目的 这里提出的研究将是使用MM模拟对溶剂进行建模 通过复杂的生物溶质施加在水上的结构，然后 比较，使用首先测量相同分子的结构 差异的同位素替代中子衍射实验。分子 要研究 实际的实验优势比肽，它们的整体生物学 重要性及其作为生物聚合物更一般模型的实用性 水合。要研究的糖分子将合成制备， 在特定位置只有单一和双同位素取代 为了详细消除损失，因为平均 使用倍数标记的溶质时的环境。 溶解的集体结构强加于溶剂水的发挥作用 在许多生物过程中的重要作用，例如蛋白质折叠，膜 形成，以及配体与蛋白质的结合。这种结构通常是 援引解释现象的所有举止，但没有任何确定的方式 实际探究此结构或指定其与 溶质拓扑。分子动力学模拟提供了一种理想的学习方式 这种结构在分子水平上，但总的来说 将计算结果与实验进行比较的方法。校长 探测液体结构的实验技术是中子衍射， 在确定电解质的结构方面非常成功 简单溶质的溶液和溶液，例如稀有气体。很遗憾， 在所有类似原子上的平均掩盖各向异性结构细节 更复杂的溶质。拟议的项目将使用合成方法 在特异性上单独代替用氘或13c的糖分子准备糖分子 位置，并用D和13C中的一个原子替换，并利用 重叠的RDFs以探测溶剂分布中的各向异性。这 然后将比较这些单个原子的径向分布函数 根据这些糖在同一高的MD模拟中计算出的 实验浓度。