Theory of mechanochemical phenomena in molecular and biomolecular systems

德克萨斯大学奥斯汀分校的Dmitrii Makarov获得了化学学部化学理论、模型和计算方法项目的奖励，研究生物和人工分子中化学和机械力之间的相互作用。Makarov和同事开发了理论和计算工具来预测拉动或挤压分子是否（以及如何）加速或抑制化学过程。生物分子机器利用化学反应的能量来执行无数的机械任务，例如，通过这些任务，它们在细胞之间运输货物，使人类心脏跳动，保护细胞免受疾病的侵害，以及制造新的分子。相反，化学家最近已经学会了如何通过拉动或推动分子来诱导不寻常的化学转化，这为设计受机械力影响时改变其性质的智能材料提供了可能性。为了理解和利用这些现象，Makarov和他的研究小组还开发了一种技术，允许实验者通过测量他们产生的微小机械力来监测分子运动。研究生和本科生都参与了这个研究项目。这项拨款支持的研究包括两个主要部分。首先，人们正在开发有效计算机械化学转化速率的方法。具体的挑战是预测反应机制如何响应机械扰动而变化，并寻找新的机械敏感分子（“机械基团”），例如，允许用弱力破坏强化学键，机械诱导加强键，机械激活释放小分子。其次，Makarov小组正在开发用于分析单分子力谱测量的理论工具，重点是生物分子折叠中实验观察到的过渡路径集合的理论表征。

Dmitrii Makarov of the University of Texas at Austin is supported by an award from the Chemical Theory, Models and Computational Methods program in the Chemistry Division to study the interplay between chemical and mechanical forces in biological and artificial molecules. Makarov and coworkers develop theoretical and computational tools for predicting whether (and how) pulling or squeezing molecules accelerates or suppresses chemical processes. Biological molecular machines use the energy of chemical reactions to perform a myriad of mechanical tasks, through which they, for example, transport cargo across cells, make human hearts beat, defend cells against diseases, and make new molecules. Conversely, chemists have recently learned how to induce unusual chemical transformations by pulling or pushing on molecules, opening up the possibility of designing smart materials that change their properties when subjected to mechanical forces. Toward understanding and utilizing these phenomena, Makarov and his research group also develop techniques allowing experimenters to monitor molecular motion by measuring the tiny mechanical forces they create. Graduate and undergraduate students are involved in this research project. The research supported by this grant includes two major components. First, methods are being developed for the efficient computation of the rates of mechanochemical transformations. The specific challenges are to predict how reaction mechanisms change in response to mechanical perturbations and to search for novel mechanosensitive molecules ("mechanophores") that allow, for example, breaking strong chemical bonds with weak forces, mechanically-induced strengthening of bonds, and mechanically-activated release of small molecules. Second, the Makarov group is developing theoretical tools for the analysis of single-molecule force spectroscopy measurements, with a focus on theoretical characterization of experimentally-observed transition-path ensembles in biomolecular folding.