RUI: Quantum Characterization of Stair-Stepped Base Stacking Interactions in tRNA

杜鲁门州立大学的Eric Patterson和Maria Nagan得到了理论和计算化学计划颁发的本科生研究奖的资助，该奖项涉及对轨道相互作用的量子力学研究，这些相互作用负责塑造在几种转移核糖核酸(TRNA)结构中发现的反密码子茎环(ASL)的阶梯区域。正在探索反密码子堆积的三个相关项目，以了解(1)序列特异性对阶梯状构象的影响，(2)动力学对统计采样的一组人类tRNALys中轨道相互作用能的影响，3以及(3)位于反密码子正上方的非标准核酸碱基在稳定反密码子方面的作用。利用密度泛函理论(DFT)在M05-2X/6-31+G(d，p)水平上结合详细的自然键轨道(NBO)分析，确定了影响这一独特结构特征的重要立体电子因素。由于通过mRNA识别tRNA对于将遗传密码正确翻译成蛋白质至关重要，因此这项工作将揭示生命系统健康运作的关键过程。这项工作是在一所以本科生为主的机构进行的，并通过专门关注本科生产生了更广泛的影响，其中一些人是代表性不足的少数族裔。PI有丰富的与本科生合作和指导的经验。合伙皮纳根是美国国家科学基金会资助的水星联盟的一部分，所以这个项目的学生也参加了水星赞助的活动。

Eric Patterson and Maria Nagan of Truman State University are funded by a Research in Undergraduate Institutions (RUI) award from the Theoretical and Computational Chemistry program for research involving quantum-mechanical studies of the orbital interactions responsible for shaping the stair-stepped region of the anticodon stem loop (ASL) found in several transfer ribonucleic acid (tRNA) structures. Three related projects of anticodon stacking are being explored to understand (1) sequence-specific effects on the stair-stepped conformation, (2) the effects of dynamics on orbital interaction energies in a statistically-sampled set of human tRNALys,3 structures and (3) the role of nonstandard nucleic acid bases positioned directly above the anticodon in stabilizing the anticodon. Significant stereoelectronic factors that influence this unique structural feature are being identified using density functional theory (DFT) at the M05-2X/6-31+G(d,p) level of theory in conjunction with detailed natural bond orbital (NBO) analysis. Because tRNA recognition by mRNA is critical to proper translation of the genetic code into proteins, this work will shed light on a process key to the healthy functioning of living systems. The work is being carried out at a predominately undergraduate institution and is having a broader impact through its exclusive focus on undergraduate students, some of whom are under-represented minorities. The PIs have significant experience working with and mentoring undergraduates. co-PI Nagan is part of the NSF-funded MERCURY consortium so students in this project are participating in MERCURY-sponsored events as well.