Abstract

Babak Khalili Hadad*, Hadis Soltani, Sara Nouroozi and Fatemeh Navaie

Development of a hepatitis C vaccine is a challenge. Although several vaccines are currently under
development, no effective vaccine is currently available. Non structural protein- NS3- can stimulate TH1 and
make enhancement in NS3-specific interferon-γ (IFN-γ) serum level. It is thought to use nanoparticles which are
biodegradable and safe to body can be a novel approach to deliver epitops as vaccine. Adding the polypeptides
components of NS3 on cyclic hexa peptide nanorings with the ability to stimulate immune system without any
risk of infection is the main goal of this research. In present study, the nano structures were designed using
Hyperchem
TM
8.0.6 software and ArgusLab 4.0.1 package. Cyclo [(-D-G3-L-D3)] nanoring has been studied by
quantum mechanical calculations within the Onsager self- consistent reaction field model at room and critical
body temperatures, using Gaussian 03 package. Radius of gyration and φ and ψ rotation were analyzed with
VMD 1.8.2. Montecarlo molecular mechanic method in both MM+ and Bio+ (Charmm) force fields were operated
in 200pSec. 1, 2 and 3 polypeptide chains of C and D, separated from NS3 of protease (PDB ID: 1NS3), were
substituted to the core. It was revealed that by increasing the polypeptide substituent, the potential energy was
increased in systems. The mean of relative potential in Cyclo [(-D-G3-L-D3)] substituted with D-polypeptide chain
was about two times more stable than the one of C- polypeptide chain, in the same condition. Φ and ψ, changes
due to temperature arising were approved in these cases. Although both C and D polypeptide chains were
stable in water medium (such as body condition), the results revealed that D chain is more stable to use for
nanovaccine fabrication. The Cyclo [(-D-G3-L-D3)] with three substituent of D-chain is suggested, based on
results.