Unraveling Connections Among Biomolecular Structure, Interfacial Solvent Dynamics, and Conformational Dynamics

化学系的化学结构，动力学和机制B计划（CSDMB）支持Katie Mitchell-Koch教授和Vinh Nguyen教授的项目。Mitchell-Koch教授是威奇托州立大学化学系的教员，Nguyen教授是弗吉尼亚理工大学物理系的教员。他们的研究重点是酶周围溶剂分子的动力学或运动。酶是影响生命系统中化学反应的分子。他们以惊人的效率和选择性这样做。他们执行这些任务的能力取决于他们的灵活性。这种灵活性受到酶表面和它所溶解的溶剂之间的相互作用的强烈影响，特别是酶的不同部分可以“滑过”该溶剂的程度。由于这些相互作用的重要性，新的人工酶的设计依赖于了解酶如何影响其表面上溶剂分子的运动，以及这些特征如何影响酶的运动和行为。考虑到这一点，Nguyen教授正在开发独特的方法，使他的团队能够同时收集溶剂运动和酶内运动的数据。为了补充这些努力，Mitchell-Koch教授采用计算化学技术来深入了解酶表面的特定特征如何改变周围溶剂的行为方式，并最终提高酶的性能。通过这种方式，这项工作有望指导蛋白质工程和新型生物催化剂的设计，以实现精细化学品和药物的绿色生产（更低的能源成本，更高的原子效率）。这项研究为本科生和研究生的跨学科培训和指导提供了宝贵的机会和资源。米切尔-科赫教授和阮教授在培训本科生和研究生方面有着良好的记录，包括那些来自STEM代表性不足的群体的学生，他们将继续招募和培训学生，为我们国家的科学和技术能力做出贡献。作为该项目的一部分，他们与中学生和高中生的外联活动将加强研究的影响。溶剂相容酶（在有机溶剂中发挥作用的酶）为研究界面溶剂动力学与分子结构、动力学和机制之间的联系提供了理想的平台，因为酶的活性受蛋白质构象动力学的影响。该项目采用世界上精度最高、灵敏度最高、连续频率最大的千兆赫到太赫兹光谱仪（功率信噪比高达1015，光谱分辨率小于100 Hz），结合分子动力学模拟，绘制蛋白质溶剂化和生物分子表面周围的分子相互作用。具有不同化学性质的溶剂作为变量，改变与表面的分子间相互作用，从而改变溶剂动力学。文献报道支持在水溶液和有机溶剂中界面溶剂动力学和蛋白质动力学之间的连接。在这项工作中，PI假设有一个反馈回路之间的结构修饰的溶剂动力学和溶剂动力学蛋白质动力学，可以作为蛋白质的设计原则。这项工作的一个区别是它专注于局部（区域特定）溶剂化环境（围绕整个蛋白质映射），而不是分析溶剂化层的整体性质（或依赖于散装溶剂特性），因为人们认为这些局部效应是溶剂动力学-生物分子结构-动力学连接的主要仲裁者。该项目首次全面研究了酶界面的有机溶剂动力学，以及它们与酶结构-动力学-活性的关系，将结果与测量的集体运动和公布的动力学值联系起来。由于溶剂化过程在电荷转移（电子和质子转移），底物传输和分子识别中也很关键，因此必须表征有机和水性溶剂动力学与表面-溶剂相互作用之间的关系，以告知许多界面的设计，从功能材料到从头蛋白质。Mitchell-Koch和Nguyen实验室为具有不同背景的本科生和研究生研究人员提供跨学科培训。外联活动使公众和社区团体了解太赫兹研究、生物分子动力学和计算化学方法。弗吉尼亚理工大学的夏季纳米营为学生，包括那些代表性不足的群体，他们的父母/监护人和学校教师，提供参与旨在促进参与和对纳米科学感兴趣的活动的能力，包括千兆赫到太赫兹科学。一个关于布朗运动的研讨会将提供实验观察和模拟数据的视频，在威奇托州一年一度的“扩大你的视野”活动中接触到中学女生。该计划也将在K-12外展介绍中提供。对更广泛影响的评估包括对研究生的纵向跟踪以及对教师/学生/家长进行外联活动调查。

The Chemical Structure, Dynamics, and Mechanism B Program (CSDMB) of the Chemistry Division supports the project by Professors Katie Mitchell-Koch and Vinh Nguyen. Professor Mitchell-Koch is a faculty member in the Department of Chemistry at Wichita State University, and Professor Nguyen is a faculty member in the Department of Physics at Virginia Tech. Their research focuses on the dynamics or movement of solvent molecules around enzymes. Enzymes are molecules that effect chemical reactions in living systems. They do so with remarkable efficiency and selectivity. Their ability to perform these tasks depends on their ability to be flexible. This flexibility is strongly influenced by interactions between the surface of the enzyme and the solvent it is dissolved in, and in particular how well different parts of the enzyme can "slip through" that solvent. Because of the importance of these interactions, the design of new artificial enzymes relies on understanding how enzymes influence the movement of solvent molecules on their surface and in turn how those features influence how the enzyme moves and behaves. With this in mind, Professor Nguyen is developing unique methods that allow his group to gather data on both solvent movement and movement within the enzyme at the same time. To compliment these efforts, Professor Mitchell-Koch employs computational chemistry techniques to provide insights into how specific features of the enzymes surface change the way the surrounding solvent behaves and ultimately improve performance of the enzyme. In this way, the work is poised to guide protein engineering and design of new biocatalysts for greener production (lower energy costs, higher atom efficiency) of fine chemicals and pharmaceuticals. The research provides valuable opportunities and resources for interdisciplinary training and mentoring of undergraduate and graduate students. Professors Mitchell-Koch and Nguyen have a strong track record of training undergraduate and graduate students including those from underrepresented groups in STEM, and they will continue to recruit and train students to contribute to our nation's capacity for science and technology. Their outreach activities with middle school and high school students as a part of the project will strengthen the impacts of the research.Solvent-compatible enzymes (those that function in organic solvents) present an ideal platform for studying connections between interfacial solvent dynamics and molecular structure, dynamics, and mechanism, since enzymatic activity is influenced by protein conformational dynamics. The project employs the world's highest precision, highest sensitivity and largest continuous-frequency gigahertz to terahertz spectrometer (with power signal-to-noise up to 1015 and spectral resolution less than 100 Hz), combined with molecular dynamics simulations to map protein solvation and molecular interactions around the surface of biomolecules. Solvents with differing chemical properties serve as variables, altering intermolecular interactions with the surface that in turn modify solvent dynamics. Literature reports support a connection between interfacial solvent dynamics and protein dynamics in both aqueous solutions and organic solvents. In this effort, the PIs hypothesize that there is a feedback loop between structure-modified solvent dynamics and solvent dynamics-protein dynamics that may serve as a protein design principle. A distinction in the work is that it focuses on local (region-specific) solvation environments (mapped around the entire protein) rather than analyzing solvation layer properties as a whole (or relying on bulk solvent characteristics), as it is thought that these local effects are the primary arbitrators of solvent dynamics-biomolecular structure-dynamics connections. The project undertakes the first comprehensive study of organic solvent dynamics at the enzyme interface, and their relationship to enzyme structure-dynamics-activity, tying results to measured collective motions and published kinetics values. Since solvation processes are also critical in charge transfer (electron and proton transfer), substrate transport, and molecular recognition, it is imperative to characterize relationships between organic and aqueous solvent dynamics and surface-solvent interactions to inform design of many interfaces, from functional materials to de novo proteins. Interdisciplinary training for undergraduate and graduate researchers with diverse backgrounds is provided in the Mitchell-Koch and Nguyen laboratories. Outreach activities provide awareness of terahertz research, dynamics of biomolecules, and computational chemistry methods to the public and community groups. The Summer NanoCamp at Virginia Tech gives students, including those in under-represented groups, their parents/guardians, and school teachers, the ability to participate in activities designed to foster engagement and interest in nanoscience, including gigahertz to terahertz science. A workshop on Brownian motion will provide experimental observations and videos of simulations data, reaching middle school girls at annual Expanding Your Horizons events at Wichita State. This program will also be available in K-12 outreach presentations. Assessment of broader impacts includes longitudinal tracking of research students and teacher/student/parent surveys for outreach activities.