Experimental Studies of Water Structuring by Sugars

描述(申请人提供)：计算机模拟已被证明是 对于研究复杂解的结构非常有用，提供了 难以或不可能通过实验手段获得的信息。‘虽然 这种详细程度是分子力学(MM)的一大优势。 计算表明，验证结果的必要性明显增加。 通过与实验进行严格的比较，对这种模拟进行了验证。的目标是 这里提出的研究将使用MM模拟来模拟溶剂 由复杂的生物溶质施加在水上的结构，然后 比较，为了测量相同分子的这种结构，首先使用 差示同位素替代中子衍射实验。这些分子 将被研究的是各种戊糖和己糖，因为它们 实用的实验优势超过了多肽，它们的整体生物学 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。将要研究的糖分子将被合成制备， 由于在特定位置只有单同位素和双同位素替代，在 为了消除因平均不同而造成的详细损失 使用多标记溶质时的环境。 溶质施加在溶剂水上的集体结构起着 在许多生物过程中发挥着深远的作用，如蛋白质折叠、膜 形成，以及配体与蛋白质的结合。这样的结构通常是 用来解释所有现象的方式，但没有任何确定的方法来解释 实际探测此结构或指定其与 溶质拓扑。分子动力学模拟提供了一种理想的研究方法 这种在分子水平上的结构，但总的来说，很少有 如何将计算结果与实验结果进行比较。校长 探测液体结构的实验技术是中子衍射， 在确定电解液的结构方面已经非常成功 稀有气体等简单溶质的溶液和溶液。不幸的是， 所有相似原子的平均掩盖了各向异性结构的细节 更复杂的溶质。拟议的项目将使用合成方法来 在特定条件下制备单取代氢或13C的糖分子 位置，D和13C各有一个原子的双取代，利用 重叠的rdf来探测溶剂分布的各向异性。这个 然后将比较这些单个原子的径向分布函数 与从这些糖类的新MD模拟计算出的结果相同 实验浓度。

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.