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

在化学系化学理论，模型和计算方法课程的支持下，William Marsh Rice大学的Anatoly Kolomeisky教授正在研究异质性在各种化学和生物过程中的影响。众所周知，相同的化学反应永远不会在相同的时间产生相同的产物-总是会有一些完成时间的分布。同样，在相同条件下，基因相同的生物细胞也不会有相同数量的相关生物分子（蛋白质、DNA、RNA、脂质等）。这种分歧的根源是化学和生物过程具有随机性，并且发生在波动的环境中。 然而，目前化学和生物过程的定量分析忽略了这种性质变化的可能性，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，而且可以作为一种强有力的工具，用于探索潜在的化学和生物过程的微观机制。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。外联活动还将包括在当地学校举办化学展览，共同组织本科生化学研究研讨会，公开讲座，以及继续与科学作家合作，以便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层次的年轻研究人员提供多学科培训计划，使他们为未来的技术和工业挑战做好准备。根据该奖项，Anatoly Kolomeisky教授及其研究小组旨在通过为几种特定现象生成定量模型，建立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。该科学计划将通过结合分析模型，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，全原子和粗粒度分子动力学模拟来进行。所获得的理论结果和预测将与实验观测进行比较，以修改和改进理论模型。具体项目将包括：（i）通过分析化学反应的动力学来研究催化机制;（ii）理解和优化抗菌肽的功能;（iii）研究异质性在癌症引发的动力学中的作用;以及（iv）研究细胞溶解的机制。 该策略将建立简单但定量的分析模型，这些模型与所有实验数据一致，澄清潜在过程的分子图像，为未来的实验提供明确的可测试预测，同时不违反化学和物理的基本定律。该奖项反映了NSF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。

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.