RUI: Solubility and Dynamic Implications for Structurally Homologous Disaccharides

在化学系化学结构、动力学和机理A （CSDM-A）项目的支持下，来自里彭学院的Christina Othon和来自里彭学院的Patrick Willoughby以及来自卫斯理大学的Erika Taylor将使用实验和计算方法研究溶液中双糖的稳定性。双糖的水合作用和动力学性质影响这些分子如何稳定蛋白质。Othon博士和她的团队将整合分子动力学模拟、生物物理分析和超快光谱来研究葡萄糖基双糖在溶液中的水合作用和动力学特性，从而了解对溶解度、氢键能力的影响，以及分子赋予溶剂的能量和动力学变化。本科生和研究生将在这些研究活动中接受培训，并将通过开发课程培训模块和研讨会活动来补充。溶剂介导的蛋白质渗透稳定的直接证据对于理解热和其他环境应激波动如何影响这些重要生物大分子的稳定性和功能是重要的。计算对接模型、圆二色性和量热测量将用于研究双糖及其立体异构体在稳定蛋白质结构的能力方面的差异。然后将使用超快荧光频率上转换光谱来评估水合动力学。这种计算和实验方法的结合有望在分子水平上理解与渗透物稳定相关的蛋白质-溶质和溶质诱导的溶剂修饰有关的优先溶剂化模型。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Structure, Dynamics, and Mechanisms A (CSDM-A) Program in the Division of Chemistry, Christina Othon from Ripon College along with Patrick Willoughby from Ripon College and Erika Taylor from Wesleyan University will use both experiments and computational methods to study the stability of disaccharides in solution. The hydration and dynamical properties of disaccharides impact how these molecules stabilize proteins. Dr. Othon and her team will integrate molecular dynamics simulations, biophysical assays, and ultrafast spectroscopy to study the hydration and dynamical properties of glucose-based disaccharides in solution so that impacts on solubility, hydrogen bonding capacity, and the energetic and kinetic changes the molecules impart to the solvent can be learned. Undergraduate and graduate students will be trained in these research activities and this will be supplemented by the development of coursework training modules and workshop activities.Direct evidence of solvent-mediated osmolyte stabilization of proteins is important for understanding how thermal and other environmental stress fluctuations influence the stability and function of these important biomacromolecules. Computational docking models, circular dichroism, and calorimetry measurements will be used to investigate how disaccharides and their stereoisomers differ in their ability to stabilize protein structure. Hydration dynamics will then be evaluated using ultrafast fluorescence frequency up-conversion spectroscopy. This combination and computational and experimental approaches are expected to result in a molecular level understanding of the preferential solvation model regarding relevant protein-solute and solute-induced solvent modification for osmolyte stabilization.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.