Theoretical Studies of the Effect of Selenium on Biochemical Signaling

无机化学、生物无机化学和金属有机化学项目的这一奖项支持老道明大学的克雷格·A·贝斯教授研究硒在生化信号过程中的作用。硒具有抗氧化性，是一种重要的微量营养素。由于硒对正常生化信号通路的潜在干扰，尤其是锌介导的转录和修复，限制了硒的使用。这个项目使用分子模拟来确定硒的有益(清除氧化还原)和有害(干扰锌信号)的作用机制。由于溶剂在水相质子转移反应中的参与，这些体系提出了一个重要的计算挑战。贝斯教授和他的同事正在实施一种溶剂辅助质子交换(SAPE)的计算技术，该技术允许对质子通过水介质的转移进行逼真的模拟。这个项目将导致对控制信号转导的氧化还原途径的生物无机基础的更深入的洞察。计算模型还提供了关于水相反应如何工作的分子视图，从而将产生适用于硒化学以外的结果。该奖项的长期广泛影响涉及到硒在预防癌症和心血管疾病方面可能发挥的潜在作用；长期结果可能指导化疗药物的开发。该奖项的教育影响更广泛，包括通过与牛津大学学生组织共同赞助的大型活动和对高中生的一对一指导，向科学界代表性不足的群体进行外联。对研究生和本科生研究人员的培训也是该项目不可或缺的一部分。

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.