CAREER: New Insights into the Reactivity of S-Nitrosothiols

有了这个奖项，生命过程化学和化学结构、动力学和机制项目将资助来自马凯特大学的Qadir Timerghazin博士研究s -亚硝基硫醇（RSNOs）的生物反应以及使用计算化学方法控制这些反应的酶控制机制。基于蛋白的RSNOs的形成是一氧化氮（NO）生物作用的主要机制之一，因此在生命科学和医学领域引起了极大的兴趣。基于对RSNO电子结构的概念认识，利用量子化学计算、分子动力学和混合量子力学/分子力学方法研究RSNO反应的蛋白质控制机制。计算预测将由实验合作者进行测试。RSNOs对生物体的正常生理和病理过程至关重要，本研究对RSNOs的生物学反应有了新的认识。在这个项目中开发的计算工具可能对其他研究人员对基于蛋白质的RSNOs的特性进行建模有用。一氧化氮（NO）是最小的分子之一，是一种非常重要的生物活性化合物，它控制着生物体的多种关键过程。一氧化氮也在一些重要药物的作用背后，如广泛用于心脏病的三硝基甘油。NO在生物学中的主要作用方式之一是形成s -亚硝基硫醇（RSNOs），而RSNOs又参与随后的生化反应。由于这些反应的实验研究具有挑战性，计算建模可以提供对这些过程的见解。在这个计算研究的过程中，研究生和本科生将获得最先进的计算化学方法的专门训练，并将参与化学、生命科学、物理学和计算机科学之间的跨学科合作。计算化学技术将紧密集成在整个本科化学课程在马奎特大学和超越。

With this award, the Chemistry of Life Processes and the Chemical Structure, Dynamics and Mechanisms Programs in the Chemistry Division are funding Dr. Qadir Timerghazin from Marquette University to investigate biological reactions of S-nitrosothiols (RSNOs) and the mechanisms of the enzymatic control of these reactions using computational chemistry methods. Formation of protein-based RSNOs is one of the main mechanisms of the biological action of nitric oxide NO, and thus of great interest in life sciences and medicine. Based on the conceptual insights into the RSNO electronic structure, the mechanisms of protein control of RSNO reactions will be studied using quantum chemistry calculations, as well as molecular dynamics and hybrid quantum mechanics/molecular mechanics methods. The computational predictions will be tested by experimental collaborators. This research seeks new insights into the biological reactions of RSNOs, which are critical for normal physiological and pathological processes in living organisms. The computational tools developed in the course of this project could be useful to other researchers for modeling the properties of protein-based RSNOs. Nitric oxide, NO, one of the smallest molecules, has been identified as a very important biologically active compound that controls a variety of key processes in living organisms. NO is also behind the action of several important drugs, such as trinitroglycerine, widely used for heart conditions. One of the main ways NO acts in biology is the formation of S-nitrosothiols (RSNOs), which in turn participate in subsequent biochemical reactions. As these reactions are challenging to study experimentally, computational modeling can provide insights into these processes. In the course of this computational research, graduate and undergraduate students will acquire specialized training in the state-of-the-art computational chemistry methods and will be involved in collaborative interdisciplinary efforts at the interface between chemistry, life sciences, physics, and computer science. Computational chemistry techniques will be tightly integrated throughout the undergraduate chemistry curriculum at Marquette University and beyond.