Rogers David M, Hirst Jonathan D
School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Biochemistry. 2004 Aug 31;43(34):11092-102. doi: 10.1021/bi049031n.
Electronic transitions in aromatic side chains are responsible for the characteristics of proteins in the near UV. We present the first systematic study of a large number of proteins focused on the accurate calculation of near-UV circular dichroism (CD) spectra. We report new parameter sets derived from ab initio calculations for benzene, phenol, and indole that describe the valence electronic transitions to the (1)L(b), (1)L(a), (1)B(b), and (1)B(a) states in the side chains of amino acids phenylalanine, tyrosine, and tryptophan. CD spectra were calculated, using the matrix method with the new side-chain parameters, for 30 proteins whose CD spectra and crystal structures have been made publicly available. The new parameter sets are fully self-consistent and yield near-UV spectra better than those obtained using previous parameter sets. The mean absolute errors for computed wild-type spectra in the near UV are reduced by a factor of approximately 2. A similiar reduction is found for the near-UV spectra (and difference spectra) of mutants involving aromatic amino acids. Empirical modifications to model vibronic coupling in the side-chain chromophore of phenylalanine offer no overall improvement. Protein CD calculations from first principles coupled with atomic-level modeling enhance the utility and interpretability of CD measurements in the near UV.
芳香侧链中的电子跃迁决定了蛋白质在近紫外区的特性。我们首次对大量蛋白质进行了系统研究，重点是精确计算近紫外圆二色性（CD）光谱。我们报告了从苯、苯酚和吲哚的从头算计算中得出的新参数集，这些参数集描述了氨基酸苯丙氨酸、酪氨酸和色氨酸侧链中向（1）L（b）、（1）L（a）、（1）B（b）和（1）B（a）态的价电子跃迁。使用带有新侧链参数的矩阵方法，计算了30种蛋白质的CD光谱，这些蛋白质的CD光谱和晶体结构已公开。新参数集完全自洽，产生的近紫外光谱比使用先前参数集获得的光谱更好。近紫外区计算的野生型光谱的平均绝对误差降低了约2倍。在涉及芳香族氨基酸的突变体的近紫外光谱（和差光谱）中也发现了类似的降低。对苯丙氨酸侧链发色团中振动耦合模型的经验修正并没有带来整体改善。基于第一原理的蛋白质CD计算与原子水平建模相结合，提高了近紫外区CD测量的实用性和可解释性。
