Computer Modeling and Other Theoretical Studies of Biopo

总结：各种高水平的实验（一维和二维NMR）和理论（朗之万和分子动力学，流体动力学和聚类分析）被应用到一对三重态，使结论是不可能达到的方法被孤立使用。 其中包括：对明显各向异性分子的平坦T1曲线的解释（翻滚时间和光谱仪频率的匹配）;势能函数的评估（syn最小值的子状态分布中的可能误差）; NOE导出距离的定量误差分析（使用MD和流体动力学评估共同假设）;最重要的是，深入了解寡糖中α和β键的相对灵活性（α键赋予分子刚性）。 详尽的表征，如这些将最终使预测的构象寡糖时，他们被绑定到蛋白质，和毒素的抑制剂的设计。这项研究的报告已提交给美国化学学会杂志发表。 从头算（即，对醚和显示糖苷键的模型化合物进行了量子力学）计算，从而改进了碳水化合物的CHARMM力场。 这项研究的报告将提交出版。 还进行了计算机建模，以支持涉及与十二烷基磷酸胆碱（DPC）胶束相关的改性蛋白质片段（I-I-C-N-N-P-H-I-I）的项目。DPC胶束和肽/胶束复合物的分子动力学模拟表明，肽平放在胶束表面上，并表现出快速重排的脂质，以适应结合肽。 这项研究的报告已被接受发表在生物聚合物。

Summary: A variety of high level experimental (one and two dimensional NMR) and theoretical (Langevin and molecular dynamics, hydrodynamics, and cluster analysis) were applied to a pair of trisaccharides, enabling conclusions that would have been impossible to reach had the methods been used in isolation. These include: an explanation of the flat T1 profiles of clearly anisotropic molecules (match of tumbling times and spectrometer frequency); evaluation of potential energy functions (possible errors in the substate distribution of the syn minima); quantitative error analysis of the NOE derived distances (use of MD and hydrodynamics to evaluate common assumptions); and, most importantly, insight into the relative flexibility of alpha and beta-linkages in oligosaccharides (alpha-linkages confer rigidity to the molecule). Exhaustive characterizations such as these will eventually enable the prediction the conformation of oligosaccharides when they are bound to proteins, and the design of inhibitors of toxins. A report of this research has been submitted for publication to the Journal of The American Chemical Society. Ab initio (i.e., quantum mechanical) calculations were carried out on ethers and a model compound exhibiting a glycosidic linkage, leading to refinements of the CHARMM force field for carbohydrates. A report of this research will be submitted for publication. Computer modeling was also carried out in support of a project involving a modified protein fragment (I-I-C-N-N-P-H-I-I) associated with a dodecylphosphocholine (DPC) micelle. Molecular dynamics simulations of DPC micelles and peptide/micelle complexes suggest that the peptide lies flat on the micelle surface, and showed rapid rearrangement of the lipids to accommodate the bound peptide. A report of this research has been accepted for publication in Biopolymers.