Folded conformation of an immunostimulating tetrapeptide rigin: high temperature molecular dynamics simulation study |
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Authors: | Ashish A Kishore R |
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Institution: | Institute of Microbial Technology, Sector 39-A, Chandigarh, 160 036, India |
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Abstract: | Employing high temperature quenched molecular dynamics (QMD) simulations the conformational energy space of an immunostimulating tetrapeptide rigin: H-Gly341-Gln-Pro-Arg344-OH, is explored. Using distance dependent dielectric ( =rij) 31 different low energy starting structures with identical sequence were computed for their conformational preferences. According to the hypothesis of O'Connors et al. J. Med. Chem. 35 (1992), 2870], 83 low-energy conformers resulted from unrestrained molecular dynamics (MD) simulations, could be classified into two energy minimized families: A and B, comprised of 64 (Pro Cγ-endo orientation) and 19 (Pro Cγ-exo orientation) structures, respectively. An examination of these families revealed the existence of a remarkably similar folded backbone conformation: torsion angles being φi+1 ≈?65°, ψi+1 ≈?65°, φi+2 ≈?65°, ψi+2 ≈?60°, characterizing a distorted type III β-turn structure across the central Gln-Pro segment. The folded conformation of rigin is devoid of a classical 1 ← 4 intra-molecular hydrogen bond nevertheless, the conformation is stabilized by an effective ‘salt-bridge’, i.e., Gly H3N+… C OO? Arg interaction. Surprisingly, in both the families the unusual folded side-chain dispositions of the Gln residue favor the formation of a unique intra-residue ‘main-chain to side-chain’ H-bond, i.e., N –H…Nε interaction, encompassing a seven-membered ring motif. The conformational attributes may be valuable in de novo construction of structure-based drug candidates having sufficient stimulating activity. |
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