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

俄克拉荷马大学的Ralph Wheeler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、路径和速率。将对气相和溶剂化的酪氨酸和色氨酸自由基和阳离子进行比较。用密度泛函理论计算了这些物种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、吲哚和吲哚基阳离子自由基侧链进行了比较。这里的目标之一是确定可用于区分芳香氨基酸自由基的不同取向的振动和ESR光谱特征。然后，分子动力学将利用自由能微扰理论以及从气相密度泛函计算得到的电荷和力常数来计算水化自由能。高活性自由基的形成和迁移与癌症的发生和衰老有关。最近蛋白质中芳香族氨基酸自由基的发现和表征表明，氨基酸自由基比人们之前怀疑的要普遍得多，也更重要。惠勒计算研究的长期目标包括了解蛋白质和多肽中自由基迁移的能量学、途径和速率所涉及的分子成分及其相互作用。

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.