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Secondary structure inducing potential of β‐amino acids: Torsion angle clustering facilitates comparison and analysis of the conformation during MD trajectories
Author(s) -
Guthöhrlein E. W.,
Malešević M.,
Majer Z.,
Sewald N.
Publication year - 2007
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20859
Subject(s) - chemistry , amino acid , cyclic peptide , dihedral angle , stereochemistry , side chain , peptide , turn (biochemistry) , molecular dynamics , amino acid residue , beta (programming language) , torsion (gastropod) , peptide sequence , computational chemistry , molecule , hydrogen bond , organic chemistry , biochemistry , medicine , surgery , computer science , gene , programming language , polymer
While numerous examples of β‐peptides—exclusively composed of β‐amino acids—have been investigated during the past decade, there are only few reports on the conformational preference of a single β‐amino acid when incorporated into a cyclopeptide. The conformational bias of β‐amino acids on the secondary structure of cyclopeptides has been investigated by NMR spectroscopy in combination with distance geometry (DG) and molecular dynamics (MD) calculations using experimental constraints. The atomic coordinate RMSD criterion usually employed for clustering of conformations after DG and MD calculations does not necessarily group similar peptide conformations, as there is an insufficient correlation between atomic coordinates and torsion angles. To improve on this shortcoming and to eliminate any arbitrary decisions during this process, a torsion angle clustering procedure has been implemented. For the cyclic pentapeptides cyclo ‐(‐Val‐β‐Hala‐Phe‐Leu‐Ile‐) 1 and cyclo ‐(‐Ser‐Pro‐Leu‐β‐Hasn‐Asp‐) 3 , the β‐amino acid is found in the central position of an extended γ‐turn (pseudo γ‐turn, Ψγ‐turn), while the β‐Hpro residue in the cyclic hexapeptide cyclo ‐(‐Ser‐β‐Hpro‐Leu‐Asn‐Ile‐Asp‐) 5 preferentially occupies position i +1 of a pseudo β‐turn (Ψβ‐turn). These results further corroborate the hypothesis of β‐amino acids being reliable inducers of secondary structure in cyclic penta‐ and hexapeptides. They can be employed in the de novo design of biologically active cyclopeptides in pharmaceutical research, since the three‐dimensional presentation of pharmacophoric groups in the side chains can be tailored by incorporation of β‐amino acids in strategic sequential positions. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 829–839, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com