Solution Structure and In Silico Binding of a Cyclic Peptide with Hepatitis B Surface Antigen

Abstract

A specific ligand targeting the immunodominant region of hepatitis B virus is desired in neutralizing the infectivity of the virus. In a previous study, a disulfide constrained cyclic peptide cyclo S(1) ,S(9) Cys-Glu-Thr-Gly-Ala-Lys-Pro-His-Cys (S(1) , S(9) -cyclo-CETGAKPHC) was isolated from a phage displayed cyclic peptide library using an affinity selection method against hepatitis B surface antigen. The cyclic peptide binds tightly to hepatitis B surface antigen with a relative dissociation constant (KD (rel) ) of 2.9 nm. The binding site of the peptide was located at the immunodominant region on hepatitis B surface antigen. Consequently, this study was aimed to elucidate the structure of the cyclic peptide and its interaction with hepatitis B surface antigen in silico. The solution structure of this cyclic peptide was solved using (1) H, (13) C, and (15) N NMR spectroscopy and molecular dynamics simulations with NMR-derived distance and torsion angle restraints. The cyclic peptide adopted two distinct conformations due to the isomerization of the Pro residue with one structured region in the ETGA sequence. Docking studies of the peptide ensemble with a model structure of hepatitis B surface antigen revealed that the cyclic peptide can potentially be developed as a therapeutic drug that inhibits the virus-host interactions.

Hepatitis B virus peptide inhibitors: solution structures and interactions with the viral capsid

“…Top ten clusters that contained the highest number of trajectories were further analyzed by selecting the trajectories with the following conditions (i) the structure has φ angles within 30°of the φ-values calculated from 3 J (H N -H α ), and (ii) the structure has an interproton distance error <0.5 Å compared to the upper boundaries of distances derived from the NOE restraints. 44 One conformation from each of the top ten clusters that suited the above criteria was then selected to form a structural ensemble and analyzed using the PROCHECK-NMR. 45 The PyMOL (Version 1.3 Schrödinger, LLC) and the Discovery Studio Visualizer 3.5 (Accelrys) were used to view the structural ensembles.…”

Novel furan‐containing peptide‐based inhibitors of protein arginine deiminase type IV (PAD4)

“…The estimated secondary structure of each peptide‐based inhibitor is shown in Table . The results showed that the peptides consisted of more than 80% random coil structure, which was characterized by the strong negative band at approximately 195 nm . In addition to the predominant random coil structure, there were 10%–16% of α‐helices and a very low percentage (<5%) of β sheets and turns in the structures of the peptides.…”