Predicted 3D Model of the Rabies Virus Glycoprotein Trimer

Abstract

The RABVG ectodomain is a homotrimer, and trimers are often called spikes. They are responsible for the attachment of the virus through the interaction with nicotinic acetylcholine receptors, neural cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR). This makes them relevant in viral pathogenesis. The antigenic structure differs significantly between the trimers and monomers. Surfaces rich in hydrophobic amino acids are important for trimer stabilization in which the C-terminal of the ectodomain plays an important role; to understand these interactions between the G proteins, a mechanistic study of their functions was performed with a molecular model of G protein in its trimeric form. This verified its 3D conformation. The molecular modeling of G protein was performed by a I-TASSER server and was evaluated via a Rachamandran plot and ERRAT program obtained 84.64% and 89.9% of the residues in the favorable regions and overall quality factor, respectively. The molecular dynamics simulations were carried out on RABVG trimer at 310 K. From these theoretical studies, we retrieved the RMSD values from Cα atoms to assess stability. Preliminary model of G protein of rabies virus stable at 12 ns with molecular dynamics was obtained.

In Silico Analysis of the Antigenic Properties of Iron-Regulated Proteins against Neisseria meningitidis

“…The protein model selected in our work (CBA09441, CAM07737, and CBA03648) recorded an ERRAT score of above 91% to indicate a low resolution of our model [57]. Although our model has low resolutions, similar results were also reported previously [57][58][59]. The protein model in this work showcased a good negative Z-score value similar to others [56].…”

Immunoinformatics‐aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019‐nCoV

“…Epitope detection in glycoproteins is often complicated by the presence of covalently attached glycans. Modeling viral glycoproteins with the associated glycans is especially challenging due to the lack of related structures, although attempts have been made in hepatitis C and rabies 24,25 . Second, similar to other RNA virus, coronavirus replication is error‐prone, with a reported mutation rate of 4 × 10 −4 substitutions per site per year in SARS‐CoV 26 .…”

Antigenic site changes in the rabies virus glycoprotein dictates functionality and neutralizing capability against divergent lyssaviruses

“…The absence of a crystal structure for the lyssavirus G precludes a thorough antigenic assessment of the lyssavirus G protein. Modelling the antigenic epitopes of lyssaviruses onto existing rhabdovirus G structures at least demonstrates that antigenic sites defined by monoclonal antibody typing for rabies are potentially located in exposed positions on the ectodomain of G[39] but this does not necessarily reflect the position or role of these regions in the mature native protein. As such the antigenic repertoire that precludes vaccine derived neutralisation for the lyssaviruses remains difficult to define.…”