Theoretical Studies of the Effect of Selenium on Biochemical Signaling

这个奖项在无机，生物无机和有机化学计划支持研究教授克雷格A。贝斯在老自治领大学研究硒在生化信号过程中的作用。 硒是一种重要的微量营养素，具有抗氧化作用。 硒的使用受到其对正常生化信号通路的潜在破坏的限制，特别是锌介导的转录和修复。 该项目使用分子建模来确定硒的有益（氧化还原清除）和有害（锌信号中断）作用的机制。 这些系统提出了一个重要的计算挑战，由于在水相质子转移反应溶剂的参与。 Bayse教授及其同事正在实施一种用于溶剂辅助质子交换（SAPE）的计算技术，该技术允许通过水介质对质子转移进行逼真的建模。 这个项目将导致更深入地了解生物无机基础的氧化还原途径，管理信号转导。 计算模型还提供了关于水相反应如何工作的分子观点，从而将产生适用于硒化学之外的结果。 该奖项的长期广泛影响涉及硒在预防癌症和心血管疾病方面的潜在作用;长期的结果可能会指导化疗药物的开发。该奖项的教育更广泛的影响包括通过与ODU的学生组织共同赞助的大型活动和高中生的一对一辅导，向科学界代表性不足的群体进行宣传。 对研究生和本科生研究人员的培训也是该项目的一个组成部分。

This award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports investigations by Professor Craig A. Bayse at Old Dominion University to study the role of selenium in biochemical signaling processes. Selenium is an important trace nutrient due to its antioxidant properties. The use of selenium is limited by its potential disruption of normal biochemical signaling pathways, especially zinc-mediated transcription and repair. This project uses molecular modeling to determine the mechanisms of both the beneficial (redox scavenging) and harmful (disruption of zinc signaling) effects of selenium. These systems present an important computational challenge due to the involvement of solvent in aqueous-phase proton transfer reactions. Professor Bayse and co-workers are implementing a computational technique for solvent-assisted proton exchange (SAPE) which allows for realistic modeling of proton transfer through an aqueous medium. This project will lead to deeper insight into the bioinorganic foundation of the redox pathways that govern signal transduction. The computational models also provide a molecular view on how aqueous phase reactions work, and thereby will generate results applicable beyond selenium chemistry. The long term broader impacts of this award relate to the potential role selenium may have in the prevention of cancer and cardiovascular disease; the results in the long term may guide the development of chemotherapeutic agents. The educational broader impacts of this award include outreach to groups underrepresented in the sciences through both large-scale events co-sponsored with student organizations at ODU and one-on-one mentoring of high school students. Training of graduate and undergraduate researchers is also an integral part of this project.