Screening of commercial cyclic peptides as inhibitor envelope protein dengue virus (DENV) through molecular docking and molecular dynamics.

Dengue virus (DENV) has spread throughout the world, especially in tropical climates. Effective treatment of DENV infection is not yet available although several candidate vaccines have been developed. Treatment at this time is only to reduce symptoms and reduce the risk of death. Therefore, antiviral treatment is much needed. Envelope protein is one of the structural proteins of DENV which is known and could be a target of antiviral inhibitors and plays a special role in the fusion process. The aim of this research is to screen the commercial cyclic peptides which are used as inhibitors of envelope protein DENV through molecular docking and molecular dynamics at 310 and 312 K. Screening of commercial cyclic peptides through molecular docking ligands obtained best 10 ligands then examined the interaction between hydrogen bonding and residue contacts of the cavity envelope protein and obtained best three ligands which could enter the cavity of envelope protein overall. The three ligands were predicted through the ADME-Tox and the best ligand obtained was BNP (7-32), porcine. The results of molecular dynamics simulations at 310 and 312 K revealed that ligand can maintain interaction with the cavity of the target.

Solution structure of a cyclic RGD peptide that inhibits platelet aggregation.

Peptides containing the Arg-Gly-Asp (RGD) sequence can inhibit platelet aggregation. Incorporation of this sequence into a cyclic peptide results in specific binding to a particular integrin. Studies of cyclic RGD peptides show that residues surrounding the RGD sequence have important effects on the selectivity of the peptide to bind with glycoprotein IIb/IIIa (GPIIb/IIIa). In this paper, we elucidate the conformation of cyclo(2,10)Ac-Gly1-Pen2-Gly3-His4-Arg5-Gly6-Asp7 -Leu8-Arg9-Cys10-Ala11-NH2 (1) by NMR and molecular dynamics simulations. This peptide inhibits platelet aggregation in a manner similar to that reported for cyclo(2,10)Gly1-Pen2-Gly3-His4-Arg5-Gly6-Asp7-Le u8-Arg9-Cys10-Ala11-OH (6) (Cheng, S. et al. J. Med. Chem. 1994, 37, 1-8), which is shown to be selective for the GPIIb/IIIa receptor. The cyclic peptide 1 exhibited a major and a minor conformer in solution. In the major conformer, the His4-Arg5-Gly6-Asp7 segment encompasses a 4-->1 hydrogen bond with a distorted type II beta-turn, and the minor conformer has turn-extended-turn. A comparison between the major conformation of this peptide and those of other cyclic RGD peptides suggests the importance of a hydrophobic residue adjacent to the RGD sequence.