Molecular shape dynamics, reaction paths and conformational transitions in biomolecules. Theory and simulations.

我们的研究计划集中于开发和应用理论和计算化学的工具来研究柔性分子中形状和动力学之间的相互作用。我们的方法以一种原始的方式融合了结构、形状、能量学和构型转变的概念：分子被视为拓扑实体，而不是处于最佳几何位置的孤立构象。通过研究这些性质如何在外部扰动下保持不变，我们建立了：(I)分子形状的稳定性，(Ii)控制构型转变开始的因素，(Iii)沿着反应路径出现的新物种，以及(Iv)用于比较这些物种的动态形状相似性的度量。分子的形状随尺度的不同而不同。对于大分子，我们使用链几何和拓扑学来监测受限聚合物和蛋白质离子中的构型转变。在较小的系统中，我们重点研究外场或核几何中的非绝热变化对量子态和电子结构的影响。我们的长期目标是将这些领域整合到一个单一的协议中，以研究生物聚合物中局部电子性质和全球构象运动之间的相互作用。预计未来五年的工作将扩展我们的方法，并将其应用于对选定现象的分析。以下主题将是我们的优先事项：(A)具有不同拓扑结构的接枝聚合物和外部驱动聚合物的构型转变。(B)无水蛋白质离子在模拟飞行时间质谱仪的条件下的稳定性和展开。(C)外场和核几何对电子过程反应路径曲率的影响。主题(A)和(B)结合聚合物理论、计算机模拟和我们的技术来研究链纠缠。主题(C)涉及与蛋白质自然状态相关的运动和局域场引起的非绝热效应。后一种分析需要计算随外场变化的相干量子态的非绝热振幅。我将继续在这些领域培训HQP，并在2010/2011年休假期间与瑞典的同事进行合作研究。

Our research program focuses on developing and applying the tools of theoretical & computational chemistry to study the interplay between shape and dynamics in flexible molecules. Our approach blends the notions of structure, shape, energetics, and configurational transitions in an original manner: molecules are seen as topological entities, instead of isolated conformers at optimal geometries. By studying how these properties persist under external perturbations, we establish: (i) the stability of molecular shape, (ii) the factors that control the onset of configurational transitions, (iii) the occurrence of new species along reaction paths, and (iv) a measure of dynamic shape similarity for comparing these species. Molecular shape is conveyed differently depending on scale. For macromolecules, we use chain geometry and topology to monitor configurational transitions in constrained polymers and protein ions. In smaller systems, we focus on how quantum states and electronic structure are affected by external fields or non-adiabatic changes in nuclear geometry. Our long-term goal is to integrate these areas into a single protocol to study the interplay between local electronic properties and global conformational motions in biopolymers. The work projected for the next five years will extend our methods and apply them to the analysis of selected phenomena. The following main themes will be our priorities: (a) Configurational transitions in grafted and externally-driven polymers with distinct topologies. (b) The stability and unfolding of anhydrous protein ions in conditions that simulate time-of-flight mass spectrometry. (c) Effect of external fields and nuclear geometry on the curvature for reaction paths for electronic processes. The themes (a) and (b) rely on a combination of polymer theory, computer simulations, and our techniques to study chain entanglement. Theme (c) deals with non-adiabatic effects caused by the motions and local fields associated with a protein native state. This latter analysis requires the computation of diabatic amplitudes in coherent quantum states that vary with external fields. I will continue to train HQPs in these areas, and pursue collaborative research with colleagues in Sweden during my sabbatical in 2010/2011.