Krishnan V V, Bentley Timothy, Xiong Alina, Maitra Kalyani
Department of Chemistry and Biochemistry, California State University, Fresno, CA 93740, USA.
Department of Medical Pathology and Laboratory Medicine, University of California School of Medicine, Davis, CA 95616, USA.
Int J Mol Sci. 2021 Jan 29;22(3):1364. doi: 10.3390/ijms22031364.
Both nuclear magnetic resonance (NMR) and molecular dynamics (MD) simulations are routinely used in understanding the conformational space sampled by peptides in the solution state. To investigate the role of single-residue change in the ensemble of conformations sampled by a set of heptapeptides, AEVXEVG with X = L, F, A, or G, comprehensive NMR, and MD simulations were performed. The rationale for selecting the particular model peptides is based on the high variability in the occurrence of tri-peptide EL between the transmembrane β-barrel (TMB) than in globular proteins. The ensemble of conformations sampled by EL was compared between the three sets of ensembles derived from NMR spectroscopy, MD simulations with explicit solvent, and the random coil conformations. In addition to the estimation of global determinants such as the radius of gyration of a large sample of structures, the ensembles were analyzed using principal component analysis (PCA). In general, the results suggest that the -EVL- peptide indeed adopts a conformational preference that is distinctly different not only from a random distribution but also from other peptides studied here. The relatively straightforward approach presented herein could help understand the conformational preferences of small peptides in the solution state.
核磁共振(NMR)和分子动力学(MD)模拟在理解溶液状态下肽段所采样的构象空间时都有常规应用。为了研究单残基变化在一组七肽(AEVXEVG,其中X = L、F、A或G)所采样的构象集合中的作用,我们进行了全面的NMR和MD模拟。选择特定模型肽的基本原理是基于跨膜β桶(TMB)中三肽EL出现的变异性高于球状蛋白。我们比较了由NMR光谱、含明确溶剂的MD模拟以及随机卷曲构象得到的三组构象集合中EL所采样的构象集合。除了估计诸如大量结构样本的回转半径等全局决定因素外,还使用主成分分析(PCA)对这些构象集合进行了分析。总体而言,结果表明-EVL-肽确实采用了一种构象偏好,这种偏好不仅明显不同于随机分布,也不同于本文研究的其他肽段。本文提出的相对直接的方法有助于理解溶液状态下小肽的构象偏好。