CAREER: New Insights into the Reactivity of S-Nitrosothiols

获得该奖项的是马奎特大学生命过程化学和化学结构、动力学和机理项目，资助他利用计算化学方法研究S亚硝硫醇(RSNO)的生物反应以及这些反应的酶控制机制。以蛋白质为基础的RSNO的形成是NO生物学作用的主要机制之一，因此引起了生命科学和医学的极大兴趣。基于对RSNO电子结构的概念性认识，将使用量子化学计算、分子动力学和混合量子力学/分子力学方法来研究蛋白质控制RSNO反应的机制。计算预测将由实验合作者进行测试。这项研究寻求对RSNO的生物学反应的新见解，RSNO对活体的正常生理和病理过程至关重要。在这个项目的过程中开发的计算工具可以对其他研究人员对基于蛋白质的RSNO的性质进行建模有用。一氧化氮，NO，是最小的分子之一，被认为是一种非常重要的生物活性化合物，控制着生物体中的各种关键过程。一氧化氮也是几种重要药物作用的幕后推手，例如被广泛用于心脏疾病的三硝酸甘油。生物学中NO作用的主要方式之一是形成S-亚硝硫醇(RSNO)，亚硝硫醇又参与随后的生化反应。由于这些反应在实验上的研究具有挑战性，计算建模可以提供对这些过程的洞察。在这项计算研究的过程中，研究生和本科生将获得最先进的计算化学方法的专门培训，并将参与化学、生命科学、物理和计算机科学之间的跨学科协作努力。计算化学技术将在马奎特大学及以后的本科化学课程中紧密结合。

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.