Schweitzer-Stenner Reinhard
Department of Chemistry, Drexel University, 32nd and Chestnut Streets, Philadelphia, Pennsylvania 19104, USA.
J Phys Chem B. 2009 Mar 5;113(9):2922-32. doi: 10.1021/jp8087644.
The conformational preference of individual amino acid residues in the unfolded state of peptides and proteins is the subject of a continuous debate. Research has mostly been focused on alanine, owing to its abundance in proteins and its relevance for the understanding of helix <----> coil transitions. In the current study, we have analyzed the amide I band profiles of the IR, isotropic and anisotropic Raman, and VCD profiles of trialanine in terms of a conformational model which, for the first time, explicitly considers the entire ensemble of possible conformations rather than representative structures. The distribution function utilized for a satisfactory simulation of the amide I band profiles was found to also reproduce a set of five J coupling constants reported by Graf et al. (Graf, J.; et al. J. Am. Chem. Soc. 2007, 129, 1179). The results of our analysis reveal a PPII fraction of approximately 0.84 for the central alanine residue, which strongly corroborates the notion that alanine has a very high PPII propensity, exceeding the values obtained from restricted coil libraries. We performed a similar analysis for trivaline and found that the dominant fraction of its central residue is a beta-strand. The fraction of the respective distribution is 0.68. The remaining fraction contains contributions from helical and PPII conformations. The results of our analysis enable us to decide on the suitability of force fields used for MD simulations of short alanine-containing peptides. The paper establishes vibrational spectroscopy as a suitable method to explore the energy landscape of amino acid residues.
肽和蛋白质未折叠状态下单个氨基酸残基的构象偏好一直是持续争论的话题。由于丙氨酸在蛋白质中含量丰富且与理解螺旋<---->卷曲转变相关，研究大多集中在丙氨酸上。在当前研究中，我们根据一种构象模型分析了三丙氨酸的红外酰胺I带谱、各向同性和各向异性拉曼光谱以及VCD谱，该模型首次明确考虑了所有可能构象的整体而非代表性结构。发现用于令人满意地模拟酰胺I带谱的分布函数还能重现Graf等人报道的一组五个J耦合常数（Graf, J.; 等人，《美国化学会志》2007年，129卷，1179页）。我们的分析结果表明，中心丙氨酸残基的PPII比例约为0.84，这有力地证实了丙氨酸具有非常高的PPII倾向这一观点，超过了从受限卷曲文库获得的值。我们对三缬氨酸进行了类似分析，发现其中心残基的主要部分是β链。相应分布的比例为0.68。其余部分包含螺旋和PPII构象的贡献。我们的分析结果使我们能够确定用于含丙氨酸短肽分子动力学模拟的力场的适用性。本文确立了振动光谱作为探索氨基酸残基能量景观的合适方法。
