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.

在化学理论，模型和计算方法的支持下，威廉·马什·赖斯大学的Anatoly Kolomeisky教授正在研究异质性在各种化学和生物学过程中的影响。众所周知，相同的化学反应永远不会在同一时间产生相同的产品 - 总会有一些分布。同样，在相同条件下的遗传相同生物细胞永远不会具有相同数量的相关生物分子（蛋白质，DNA，RNA，脂质等）。这种差异的起源是化学和生物过程具有随机性质，并且发生在波动的环境中。但是，当前对化学和生物过程的定量分析忽略了性质变化的可能性，这主要是由于缺乏适当的理论方法。 Kolomeisky教授将探讨以下假设：化学性质的差异不仅可以被充分考虑，而且可以用作探测基本化学和生物过程的微观机制的强大工具。 Kolomeisky教授将为来自代表性不足的团体的高中和本科生提供机会参加这项研究，并为他们的未来职业获得宝贵的培训和经验。外展活动还将包括在当地学校展示化学节目，组织化学研究研讨会，公开讲座的共同组织，以及与科学作家的持续合作，以将所获得的知识传播给公众。该项目的广播公司的影响将包括针对不同级别的年轻研究人员的多学科培训计划，这将为未来的技术和工业挑战做好准备。在此奖项之后，Anatoly Kolomeisky教授及其研究小组旨在开发一个全面的理论框架，以通过生成多种特定的定量模型来了解异质性在化学和生物学过程中的作用。科学计划将通过结合分析模型（例如化学主方程和平均场化学运动方法，数值计算，机器学习和数据分析）以及蒙特卡洛（Monte Carlo）以及全原子和粗粒分子动力学模拟。获得的理论结果和预测将与实验观察结果进行比较，以修改和改善理论模型。特定项目将包括：（i）通过分析化学反应动力学来研究催化机制； （ii）理解和优化抗菌胡椒的功能； （iii）研究异质性在癌症倡议动力学中的作用； （iv）研究细胞裂解的机制。该策略将是构建与所有实验数据一致的简单但定量的分析模型，阐明基本过程的分子图片，为将来的实验提供明确的可测试预测，同时均未违反基本的化学和物理定律。成功完成拟议的工作将提高人们对基本化学和生物学过程的了解。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子优点和更广泛的影响评估标准来评估值得支持。