Theory of Single-molecule Chemical Dynamics

德克萨斯大学奥斯汀分校的Dmitrii E. Makarov获得了化学学部化学理论、模型和计算方法项目的奖励。生物分子和它们的集合就像机器一样，在生物体中执行无数的任务。这些任务包括其他分子的合成、细胞间货物的运输、机械力的产生、识别、信号传递等。对这些功能的微观化学基础的理解将使生物灵感材料和纳米机器的设计成为可能。这样的理解为疾病的分子起源提供了重要的见解。实现这一目标的一个关键挑战是，许多分子运动，例如分子马达的“功率冲程”，既太快，无法通过直接实验观察，又太慢，无法在计算机上建模。马卡罗夫的研究小组利用理论弥合了单分子研究的实验观察和生物分子实际活动的计算机模拟之间的差距。通过实验，理论和分子模拟之间的协同作用，他们正在开发准确的模型和理论来描述直接从实验观察推断的生物分子的运动。该项目将通过组织分子动力学暑期学校、组织德克萨斯大学奥斯汀分校的生物物理学日、让本科生参与PI的小组研究活动以及让学生参加科学会议，来加强教育和研究的整合。拓展工作将包括在德克萨斯州为弱势群体服务的大学举行讲座，目的是与学生和教师建立关系，并指导一支由中学生和高中生组成的具有竞争力的科学奥林匹克队。近年来发现的生物分子相互作用新机制的研究对生物技术和高韧性生物激发材料的开发具有重要意义。这项拨款支持的研究包括两个主要部分。在第一个组成部分中，正在开发多个时间尺度和不同水平（从原子到粗、低维）理论描述的微观生物分子动力学的连贯图像，重点是内在无序蛋白质的链内动力学，生物分子折叠和蛋白质结合，特别是“模糊”蛋白质复合物的形成。第二个部分侧重于非平衡过程中屏障跨越的动力学，例如那些潜在的分子机器的作用，其目标是揭示潜在的动力学，超越离散状态和跃迁速率，从高时间分辨率的单分子数据。该小组还试图阐明分子机器如何打破向前和向后运动之间的对称性。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。

Dmitrii E. Makarov of the University of Texas at Austin is supported by an award from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry. Biomolecules and their assemblies act as machines, performing myriads of tasks in living organisms. These tasks include the synthesis of other molecules, the transport of cargo across cells, generation of mechanical forces, recognition, signaling and others. An understanding of the microscopic chemical basis of these functions will enable the design of bioinspired materials and nanomachines. Such understanding provides important insights into the molecular origins of diseases. A key challenge to achieving this goal is that many molecular motions, e.g. the “power stroke” of a molecular motor, are both too fast to observe via direct experiments and too slow to model on a computer. The Makarov research group uses theory to bridge the gap between experimental observations in single molecule studies and computer simulations of biomolecules in action. Through synergy between experiments, theory, and molecular simulations, they are developing accurate models and theories to describe the motion of biomolecules as inferred directly from experimental observations. This project will increase integration of education and research through organization of a Summer School on molecular kinetics, organization of the Biophysics Day at UT Austin, involvement of undergraduate students in the PI's group research activities, and participation of students in scientific meetings. Outreach efforts will include talks at Texas universities serving underrepresented groups, with the goal to establish relationships with students and faculty, and mentoring a competitive Science Olympiad team of middle and high school students. The studies of the recently discovered novel mechanism of biomolecular interactions may have important implications in the biotechnology, as well as for the development of bioinspired materials with high toughness.The research supported by this grant includes two major components. In the first component, a coherent picture of microscopic biomolecular dynamics at multiple timescales and at different levels (from atomistic to coarse, low-dimensional) of theoretical description is being developed, with the focus on the intrachain dynamics of intrinsically disordered proteins, biomolecular folding, and protein association, especially the formation of “fuzzy” protein complexes. The second component focuses on the dynamics of barrier crossing in nonequilibrium processes such as those underlying the action of molecular machines, with the goal to uncover underlying dynamics, beyond discrete states and transition rates, from high-temporal-resolution single-molecule data. The group also seeks to elucidate how molecular machines break the symmetry between the forward and backward motion.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.