Extensive conformational searches of 13 representative dipeptides and an efficient method for dipeptide structure determinations based on amino acid conformers

Abstract

Conformations of peptides are the basis for their property studies and the predictions of peptide structures are highly important in life science but very complex in practice. Here, thorough searches on the potential energy surfaces of 13 representative dipeptides by considering all possible combinations of the bond rotational degrees of freedom are performed using the density functional theory based methods. Careful analyses of the conformers of the 13 dipeptides and the corresponding amino acids reveal the connections between the structures of dipeptide and amino acids. A method for finding all important dipeptide conformers by optimizing a small number of trial structures generated by suitable superposition of the parent amino acid conformations is thus proposed. Applying the method to another eight dipeptides carefully examined by others shows that the new approach is both highly efficient and reliable by providing the most complete ensembles of dipeptide conformers and much improved agreements between the theoretical and experimental IR spectra. The method opens the door for the determination of the stable structures of all dipeptides with a manageable amount of effort. Preliminary result on the applicability of the method to the tripeptide structure determination is also presented. The results are the first step towards proving Anfinsen's hypothesis by revealing the relationships between the structures of the simplest peptide and its constituting amino acids. It implies that the structures of peptides are not only determined by their amino acid sequences, but also closely linked with the amino acid conformations.

Comprehensive Conformational Studies of Five Tripeptides and a Deduced Method for Efficient Determinations of Peptide Structures

“…Firstly, the trial tripeptide conformers are generated by jointing constituting amino acid(s) or dipeptide conformers based on the dipeptide structure construction strategy proposed before. 22 These trial conformers are then being optimized to get the stable tripeptide conformers. Secondly, a set of low energy conformers are processed by rotating the N-terminus C α -C bond and a subset of conformers whose middle residue has C7eq/C7ax structure are processed by rotating the middle C α -C bond by suitable degrees.…”

“…For dipeptides, the above process was shown to be enough to reproduce all important conformers in our all test cases. 22 For tripeptides, the N- or C-terminus conformers mentioned above could be replaced with the corresponding dipeptide conformers and the same process follows. Moreover, the C α -C bonds of the low energy child conformers are further being rotated to yield new trial structures (mutation) so that all important tripeptide conformers can be located.…”

“…This set of tripeptides was chosen because the conformers of their constituting amino acids and dipeptides had mostly been thoroughly studied before, 9,22,46-48 allowing a detailed comparison among the conformers of tripeptides and their constituting segments. Similar to our previous studies on dipeptides, close connections between tripeptide conformers and dipeptides or amino acid conformers were found.…”

Effects of Microsolvating Water on the Stability of Zwitterionic vs. Canonical Diglycine

“…The four conformers, (ca-1), (ca-2), (ca-3), (ca-4) agree well with those reported by Lin and co-workers. 9 The energies of the three lowest conformers (ca-1), (ca-2) and (ca-3) are quite close (within 0.6 kcal/mol), whereas those of (ca-4) and (ca-5) are higher than that of (ca-1) by ~1.6 kcal/mol. The structures (ca-1), (ca-2), (ca-3), (ca-5) are quite similar, with the terminal -NH 2 , -C=O and -NH groups in peptide bond positioned in zigzag fashion.…”

Computational Exploration of Conformations of Glycine-Arginine and a Deduced Model on Global Minimum Configurations of Dipeptides in Gas Phase

“…The result is also intriguing as zwitterions in gas phase were thought to be possible only for much larger oligopeptides with back bond chains much longer than that of ArgGly. For example, the stable conformations for many tri-and tetra-peptides are known to take the canonical form [10,11]. These results indicate that the side chain of arginine (Arg) has a strong influence on the stability of zwitterions in the gas phase.…”