Quantifying the Role of Heterogeneity in Mechanisms of Chemical and Biological Processes

量化化学和生物过程机制中异质性的作用

• 批准号: 2246878
• 负责人: Anatoly Kolomeisky
• 金额: $ 53万
• 依托单位: William Marsh Rice University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2246878&HistoricalAwards=false
• 关键词: Quantifying; Role; Heterogeneity; Mechanisms; Chemical

With support from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry, Professor Anatoly Kolomeisky of William Marsh Rice University is investigating the effects of heterogeneity in various chemical and biological processes. It is known that identical chemical reactions will never produce the same products at the same times – there will be always some distributions of completion times. Similarly, genetically identical biological cells under the same conditions will never have the same numbers of relevant biological molecules (proteins, DNA, RNA, lipids, etc.). The origin of such divergence is the reality that chemical and biological processes have a random nature and occur in fluctuating environments. Current quantitative analysis of chemical and biological processes, however, neglects the possibility of such variations in properties, mostly due to the lack of proper theoretical methods. Professor Kolomeisky will explore the hypothesis that the divergence in chemical properties not only can be fully accounted for but also might be used as a powerful tool in probing the microscopic mechanisms of underlying chemical and biological processes. Professor Kolomeisky will provide opportunities for high school and undergraduate students from underrepresented groups to participate in this research and to gain valuable training and experience for their future careers. Outreach activities will also include the presentation of chemical shows in local schools, co-organization of an undergraduate chemistry research symposium, public lectures, and continued collaboration with science writers in order to disseminate the obtained knowledge to a general public. The broader impacts of this project will include a multidisciplinary training program for young researchers of different levels that will prepare them better for future technological and industrial challenges.Under this award, Professor Anatoly Kolomeisky and his research group aim to develop a comprehensive theoretical framework to understand the role of heterogeneity in chemical and biological processes by generating quantitative models for several specific phenomena. The scientific program will be pursued by combining analytical models such as chemical master equations and mean-field chemical-kinetic methods, numerical calculations, machine learning and data analysis, as well as Monte Carlo, and full-atomic and coarse-grained molecular dynamics simulations. Obtained theoretical results and predictions will be compared with experimental observations to modify and improve theoretical models. Specific projects will include: (i) investigation of the mechanisms of catalysis by analyzing dynamics of chemical reactions; (ii) understanding and optimizing the function of antimicrobial peptides; (iii) studying the role of heterogeneity in the dynamics of cancer initiation; and (iv) investigating mechanisms of cell lysis. The strategy will be to build simple yet quantitative analytical models that are consistent with all experimental data, clarify the molecular picture of underlying processes, provide clear testable predictions for future experiments, all the while not violating basic laws of chemistry and physics. Successful completion of the proposed work will advance knowledge of fundamental chemical and biological processes.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.

在化学系化学理论、模型和计算方法项目的支持下，威廉·马什·赖斯大学的Anatoly Kolomeisky教授正在研究各种化学和生物过程中异质性的影响。众所周知，完全相同的化学反应永远不会在相同的时间产生相同的产品--总会有一些完成时间的分布。同样，基因相同的生物细胞在相同的条件下永远不会有相同数量的相关生物分子(蛋白质、DNA、RNA、脂类等)。这种差异的根源是这样一个现实，即化学和生物过程具有随机性，发生在波动的环境中。然而，目前对化学和生物过程的定量分析忽略了性质发生这种变化的可能性，这主要是由于缺乏适当的理论方法。Kolomeisky教授将探索这样一种假设，即化学性质的差异不仅可以完全解释，而且可能被用作探索潜在化学和生物过程的微观机制的有力工具。Kolomeisky教授将为来自代表性不足群体的高中生和本科生提供参与这项研究的机会，并为他们未来的职业生涯获得宝贵的培训和经验。外展活动还将包括在当地学校举办化学展览，共同举办本科生化学研究研讨会，公开讲座，以及继续与科学作者合作，向公众传播所获得的知识。该项目的更广泛影响将包括为不同水平的年轻研究人员提供多学科培训计划，使他们更好地为未来的技术和工业挑战做好准备。在这一奖项下，Anatoly Kolomeisky教授和他的研究小组旨在通过为几个特定现象生成量化模型，来开发一个全面的理论框架，以了解异质性在化学和生物过程中的作用。科学计划将结合分析模型，如化学主方程和平均场化学动力学方法，数值计算，机器学习和数据分析，以及蒙特卡罗，以及全原子和粗粒度分子动力学模拟。获得的理论结果和预测将与实验观测结果进行比较，以修正和改进理论模型。具体项目将包括：(I)通过分析化学反应动力学来研究催化机制；(Ii)了解和优化抗菌肽的功能；(Iii)研究异质性在癌症启动动力学中的作用；以及(Iv)研究细胞溶解的机制。战略将是建立与所有实验数据一致的简单但定量的分析模型，澄清潜在过程的分子图景，为未来的实验提供明确的可检验预测，同时不违反化学和物理的基本定律。拟议工作的成功完成将促进对基本化学和生物过程的了解。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。