CAREER: New Insights into the Reactivity of S-Nitrosothiols

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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.