Bioinformatics approach for prediction and analysis of the Non-Structural Protein 4B (NSP4B) of the Zika virus

Mohamed E Hasan; Aya Samir; Magdy M Khalil; Medhat W Shafaa

doi:10.1016/j.jgeb.2023.100336

Bioinformatics approach for prediction and analysis of the Non-Structural Protein 4B (NSP4B) of the Zika virus

J Genet Eng Biotechnol. 2024 Mar;22(1):100336. doi: 10.1016/j.jgeb.2023.100336. Epub 2024 Feb 2.

Authors

Mohamed E Hasan¹, Aya Samir², Magdy M Khalil³, Medhat W Shafaa²

Affiliations

¹ Bioinformatics Department, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City 32897, Egypt. Electronic address: mohamed.hasan@genbri.usc.edu.eg.
² Physics Department, Medical Biophysics Division, Faculty of Science, Helwan University, Cairo, Egypt.
³ Physics Department, Medical Biophysics Division, Faculty of Science, Helwan University, Cairo, Egypt; School of Biotechnology, Badr University in Cairo, Egypt.

Abstract

Background: The Nonstructural Protein (NSP) 4B of Zika virus of 251 amino acids from (ZIKV/Human/POLG_ZIKVF) with accession number (A0A024B7W1), Induces the production of Endoplasmic Reticulum ER-derived membrane vesicles, which are the sites of viral replication. To understand the physical basis of how proteins fold in nature and to solve the challenge of protein structure prediction, Ab-initio and comparative modeling are crucial tools.

Results: The systematic in silico technique, ThreaDom, had only predicted one domain (4 - 190) of NSP4B. I-TASSER, and Alphafold were ranked as the best servers for full-length 3-D protein structure predictions of NSP4B, where the predicted models were evaluated quantitatively using benchmarked metrics including C-score (-3.43), TM-score (0.77949), RMSD (2.73), and Z-score (1.561). The functional and protein binding motifs were realized using motif databases, secondary and surface accessibility predictions combined with Post-Translational Modification Sites (PTMs) prediction. Two highly conserved protein-binding motifs (Flavi NS4B and Bacillus papRprotein), together with three (PTMs) (Casein Kinase II, Myristyl site, and ASN-Glycosylation site) were predicted utilizing the Motif scan and Scanprosite servers. These patterns and PTMs were associated with NSP4B's role in triggering the development of the viral replication complex and its participation in the localization of NS3 and NS5 on the membrane. Only one hit from Structural Classification of Protein (SCOP) matched the protein sequence at positions 10 to 397 and was categorized six-hairpin glycosidases superfamily according to CATH (Class, Architecture, Topology, and Homology). Integrating this NSP4B information with the templates' SCOP and CATH annotations achieves it easier to attribute structure-function/evolution links to both previously known and recently discovered protein structures.

Keywords: (NS4B); AlphaFold; I-TASSER; SCOP and CATH; Zika virus.