Helix and H-bond formations of alanine-based peptides containing basic amino acids

Abstract

We studied comprehensively the helicity and H-bonding evolutions during the folding processes of Lysand Arg-containing alanine-based peptides. The evolution of a-helical conformation concerning the entire sequence and each amino acid residue was examined, as well as the helix-forming propensities were characterized. The formation of various types of the intramolecular H-bonds was also investigated, pointing out the helix-stabilizing role of local interactions and the destabilizing role of non-local interplays. Our study led to the observation that the nonlocal H-bonds affected the evolution of helical conformations, as well as the entire folding processes.

Characterizing the structural and folding properties of long‐sequence hypomurocin B peptides and their analogs

“…Based on the crystal structure of alamethicin, a similar secondary structural motif was observed for this most extensively studied, long‐sequence peptaibol composed of 20 amino acids . These results pointed out that alamethicin could be characterized by mainly α‐helical structure, which possessed a small distortion generated by the Pro amino acid. Consequently, this peptaibol molecule adopted a conformation, for which the two helical segments found in the N‐ and C‐terminal parts of alamethicin, respectively, were linked by a bend structure near the Pro residue located at position 14.…”

“…For the HM B peptides and their analogs, the evolution of different helical structures was examined, as follows: (i) 3 10 ‐helix, (ii) α‐helix, and (iii) left‐handed α‐helix. In the case of each conformation of peptides, with regard to each snapshot of the MD trajectories, the following formula was used to calculate the percentages of various helical contents (i.e., helicities, f ): where n h is the number of amino acid residues satisfying the torsion angle criteria for the various helical conformations, which were as follows: (i) Φ = −60º ± 30º and Ψ = −30º ± 30º for the 3 10 ‐helix, (ii) Φ = −60º ± 30º and Ψ = −50º ± 30º for the α‐helix, and (iii) Φ = 60º ± 30º and Ψ = 50º ± 30º for the left‐handed α‐helix . The N is the number of all amino acid residues found in the sequences of peptides, namely, N = 18 for the HM B peptides and their analogs.…”

“…To characterize the helix‐forming propensities of peptides, average helicities ( f AVE ‐s) were calculated for the ensemble of 100 individual MD calculations, as follows: where n h i is the number of amino acid residues located in certain helical region for the i th MD trajectory, N is the same as for the previous formula, such as N = 18, and M is the number of individual MD simulations, such as M = 100. The f AVE values were calculated for the 3 10 ‐, α‐, and left‐handed α‐helices, respectively, and they were labeled as f AVE (3 10 ), f AVE (α), and f AVE (Lα), respectively.…”

“…The 3 10 ‐, α‐, and left‐handed α‐helical contents averaged over the 100 individual MD trajectories were calculated not only for the whole conformation, but also for each amino acid residue of the HM B peptides and their analogs. The alterations of different average helicities per residue as a function of simulation time were illustrated in contour plots (see Figures ), which type of representation was earlier used for Lys‐ and Arg‐containing Ala‐based peptides, as well as for long‐sequence trichobrachin molecules …”

In Silico Conformational Analysis of the Short-Sequence Hypomurocin A Peptides

“…In the case of two types of the helical conformations mentioned above, the typical ranges of Φ and Ψ torsion angles overlap with each other; thus the cumulative helical content was also calculated, using the combined ranges of Φ and Ψ torsion angles characteristic to the 3 10 - and α -helices. In order to characterize the evolving helical structures, the percentages of helical contents (i.e., helicities) were calculated for each conformer derived from the SA calculations, applying the following formula [ 17 , 18 ]: where f is the helicity and n h is the number of amino acids satisfying the torsion angle criteria for the 3 10 - and α -helical conformations and the cumulative helical content, respectively. For simplicity, in this study, N is not equal to the number of all amino acids (i.e., 11 residues) found in the sequences of HM A peptides, as it was previously used [ 17 , 18 ].…”