Abstract
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 E*L between the transmembrane β-barrel (TMB) than in globular proteins. The ensemble of conformations sampled by E*L 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.
Highlights
The direct relationship of the protein’s structure to its function plays an essential evolutionary role in deciding the choice of certain unique combinations of amino acids creating the primary structure leading to a specific three-dimensional conformation
Though peptides can be designed to adopt a specific three-dimensional structure, single mutations in the peptide sequences may influence larger conformational changes. In this manuscript, we explore the conformational preferences of a set of model heptapeptides using a combination of nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations
A theoretical calculation of primary structures suggested that certain dipeptide motifs have relatively less occurrence in transmembrane β-barrel proteins than in globular proteins
Summary
The direct relationship of the protein’s structure to its function plays an essential evolutionary role in deciding the choice of certain unique combinations of amino acids creating the primary structure leading to a specific three-dimensional conformation. Peptides are dynamic and are known to be important in many functional applications in biomedical sciences [2]. Though peptides can be designed to adopt a specific three-dimensional structure, single mutations in the peptide sequences may influence larger conformational changes. To understand such changes, in this manuscript, we explore the conformational preferences of a set of model heptapeptides using a combination of nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations. The resultant ensembles were compared with reference to an ensemble of structures if the peptides were to assume random coil conformations
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