Folded conformation of an immunostimulating tetrapeptide rigin: high temperature molecular dynamics simulation study.

Ashish, A and Kishore, Raghuvansh (2002) Folded conformation of an immunostimulating tetrapeptide rigin: high temperature molecular dynamics simulation study. Bioorganic & medicinal chemistry, 10 (12). pp. 4083-90. ISSN 0968-0896

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Abstract

Employing high temperature quenched molecular dynamics (QMD) stimulations the conformational energy space of an immunostimulating tetrapeptide rigin: H-Gly341-Gln-Pro-Arg344-OH, is explored. Using distance dependent dielectric (epsilon =r(ij)) 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 C(gamma)-endo orientation) and 19 (Pro C(gamma)-exo orientation) structures, respectively. An examination of these families revealed the existence of a remarkably similar folded backbone conformation: torsion angles being phi(i+1) approximately -65 degrees, psi(i+1) approximately -65 degrees, phi(i+2) approximately -65 degrees, psi(i+2) approximately -60 degrees, characterizing a distorted type III beta-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 H(3)N(+)...C(alpha)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(alpha)-H...N(epsilon) 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.

Item Type:	Article
Additional Information:	Copyright of this article belongs to Elsevier Science.
Subjects:	Q Science > QD Chemistry
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	05 Jan 2012 15:11
Last Modified:	08 Jan 2015 09:47
URI:	http://crdd.osdd.net/open/id/eprint/260

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