Gas- and Solution-Phase Properties of Aromatic Amino Acid Radicals

拉尔夫·惠勒，俄克拉何马大学，由理论和计算化学计划资助，研究芳香氨基酸自由基的气相和溶液相性质。惠勒将使用从头算量子计算和分子动力学来进一步了解蛋白质和多肽中自由基迁移的能量学、途径和速率。将比较气相和溶剂化的酪氨酸和色氨酸自由基和阳离子。密度泛函理论将用于计算这些物质的气相振动频率和自旋密度，并与有机苯氧基、苯氧基阳离子、吲哚基和吲哚基阳离子自由基侧链进行比较。本文的目的之一是确定振动和ESR光谱特征，这些特征可用于区分芳香氨基酸自由基的不同取向。然后将分子动力学用于利用自由能摄动理论计算水化的自由能，并结合由气相密度泛函计算得到的电荷和力常数。高活性自由基的形成和迁移与致癌和衰老有关。最近在蛋白质中发现和表征芳香氨基酸自由基，表明氨基酸自由基比以前所认为的更为普遍和重要。惠勒计算研究的长期目标包括了解分子成分及其相互作用，这些分子成分负责蛋白质和多肽的能量学、途径和自由基迁移速率。

Ralph Wheeler, University of Oklahoma, is funded by the Theoretical and Computational Chemistry Program to study the gas phase and solution phase properties of aromatic amino acid radicals. Wheeler will use ab initio quantum calculations and molecular dynamics to further understand the energetics, pathways, and rates of radical migration in proteins and peptides. Comparisons will be made between gas phase and solvated tyrosine and tryptophan radicals and cations. Density functional theory will be used to calculate the gas phase vibrational frequencies and spin densities of these species for comparison with organic phenoxyl, phenoxyl cation, indoyl and indoyl cation radical side chains. One of the objectives here is to identify vibrational and ESR spectroscopic features which can be used to distinguish different orientations of the aromatic amino acid radicals. Molecular dynamics will then be used to compute free energies of hydration using free energy perturbation theory together with charges and force constants obtained from the gas phase density functional calculations. The formation and migration of highly reactive radicals is implicated in carcinogenesis and aging. The recent discovery and characterization of aromatic amino acid radicals in proteins implies that amino acid radicals are much more prevalent and important than previously suspected. The long term goals of Wheeler's computational research include understanding the molecular components and their interactions responsible for the energetics, pathways, and rates of radical migration in proteins and peptides.