Complex role of solvation in protein structure and dynamics in micelles and membranes

生物化学的一个巨大挑战是发展对蛋白质结构如何影响功能的基本理解。通过将蛋白质封装在表面活性剂胶束（纳米级分子聚集体，如胶体系统中的液滴）中，实验研究表明可以获得对蛋白质结构，动力学和功能的关键见解。然而，目前还没有人知道胶束环境如何影响被封装蛋白的结构和动力学。在这个由化学学部化学理论、模型和计算方法项目资助的项目中，波士顿大学的John Straub教授领导了一项计算研究，以发展对胶束中蛋白质封装的本质和潜在应用的基本理解。该项目包括对不同表面活性剂性质对胶束封装蛋白质的结构和动力学的影响进行系统的计算研究。通过一种新的多尺度计算方法，将探索表面活性剂（阴离子、阳离子和混合物）的影响以及一般（约束几何、空间依赖的压力分布）和表面活性剂特定贡献对缔合平衡、水合动力学和通道功能等性质的相对影响。将采用新颖和传统的方法来分析结构、动力学和功能，并与核磁共振和振动光谱的观测结果进行比较。这项研究的更广泛的影响是通过在生物分子结构和动力学领域发展最先进的计算和实验方法的研究生培训暑期学校来促进计算生物物理学的研究生教育。参与的学生将被挑选出来，以提供实验者和理论家，女性和男性的平衡，并有代表性不足的少数民族的强烈参与。

One of the great challenges in biological chemistry is to develop a fundamental understanding of how protein structure informs function. By encapsulating proteins in surfactant micelles (nanoscale molecular aggregates, such as a droplet in a colloidal system), experimental studies have shown that critical insights can be gained into protein structure, dynamics, and function. Currently, however, no one knows how the micelle environment influences the structure and dynamics of the encapsulated proteins. In this project, funded by the Chemical Theory, Models and Computational Methods Program of the Chemistry Division, Professor John Straub of Boston University leads a computational study to develop a fundamental understanding of the nature and potential applications of protein encapsulation in micelles.The project involves a systematic computational study of the effect of varying surfactant properties on the structure and dynamics of micelle encapsulated proteins. Through a novel multiscale computational approach, the influence of surfactant (anionic, cationic, and mixtures) and relative impact of generic (confinement geometry, spatially-dependent pressure profile) and surfactant specific contributions, on properties such as association equilibria, hydration dynamics, and channel function, will be explored. Novel and traditional approaches will be employed to analyze structure, dynamics, and function for comparison with observables from NMR and vibrational spectroscopy. The broader impact of the study is the promotion of graduate education in computational biophysics through the development of a summer school for graduate training in state-of-the-art computational and experimental methods in the field of biomolecular structure and dynamics. Participating students will be selected to provide a balance of experimentalists and theorists, women and men, with a strong involvement of underrepresented minorities.