Istituto per i Processi Chimico Fisici, Consiglio Nazionale delle Ricerche, Area della Ricerca di Pisa, via G. Moruzzi, 1 56124 Pisa, Italy.
J Phys Chem B. 2010 Mar 25;114(11):3965-78. doi: 10.1021/jp907502n.
Conformational properties of small, flexible peptides are a matter of ongoing interest since they can be considered as models for unfolded proteins. However, the investigation of the conformations of small peptides is challenging as they are ensembles of rapidly interconverting conformers; moreover, the different methods used are prone to different approximations and errors. In order to obtain more reliable results, it is prudent to combine different techniques; here, molecular dynamics (MD) simulations together with nuclear magnetic resonance (NMR), Fourier transform IR (FTIR), polarized Raman, and vibrational circular dichroism (VCD) measurements were used to study the conformational propensity of phenylalanine in the tripeptides AFA and GFG, motivated by the relevance of phenylalanine for the self-aggregation of peptides. The results of this analysis indicate that the F residue predominantly populates the beta-strand (beta) and polyproline II (PPII) conformations in both AFA and GFG. However, while phenylalanine exhibits a propensity for beta-strand conformations in GFG (0.40 < or = beta population < or = 0.69 and 0.29 < or = PPII population < or = 0.42), the substitution of terminal glycines with alanine residues induces a higher population of PPII (0.31 < or = beta population < or = 0.50 and 0.37 < or = PPII population < or = 0.57).
小而灵活的肽的构象性质是一个持续关注的问题，因为它们可以被视为未折叠蛋白质的模型。然而，由于它们是快速相互转化构象的集合，因此研究小肽的构象具有挑战性；此外，所使用的不同方法容易受到不同的近似和误差的影响。为了获得更可靠的结果，明智的做法是结合使用不同的技术；在这里，使用分子动力学（MD）模拟以及核磁共振（NMR）、傅里叶变换红外（FTIR）、偏振拉曼和振动圆二色性（VCD）测量来研究三肽 AFA 和 GFG 中苯丙氨酸的构象倾向，这是因为苯丙氨酸与肽的自聚集有关。该分析的结果表明，在 AFA 和 GFG 中，F 残基主要占据β-链（β）和多脯氨酸 II（PPII）构象。然而，虽然苯丙氨酸在 GFG 中表现出β-链构象的倾向（0.40 <或=β构象的比例<或=0.69 和 0.29 <或= PPII 构象的比例<或=0.42），但用丙氨酸残基取代末端甘氨酸会诱导更高比例的 PPII（0.31 <或=β构象的比例<或=0.50 和 0.37 <或= PPII 构象的比例<或=0.57）。
