title: Structure and sequence based functional annotation of Zika virus NS2b protein: Computational insights.
abstract: While Zika virus (ZIKV) outbreaks are a growing concern for global health, a deep understanding about the virus is lacking. Here we report a contribution to the basic science on the virus- a detailed computational analysis of the non structural protein NS2b. This protein acts as a cofactor for the NS3 protease (NS3Pro) domain that is important on the viral life cycle, and is an interesting target for drug development. We found that ZIKV NS2b cofactor is highly similar to other virus within the Flavivirus genus, especially to West Nile Virus, suggesting that it is completely necessary for the protease complex activity. Furthermore, the ZIKV NS2b has an important role to the function and stability of the ZIKV NS3 protease domain even when presents a low conservation score. In addition, ZIKV NS2b is mostly rigid, which could imply a non dynamic nature in substrate recognition. Finally, by performing a computational alanine scanning mutagenesis, we found that residues Gly 52 and Asp 83 in the NS2b could be important in substrate recognition.
authors.affiliation: Universidad San Francisco de Quito, Instituto de Simulación Computacional (ISC-USFQ), Diego de Robles sn y Vía Interoceánica, 17-1200-841, Quito, Ecuador; Universidad San Francisco de Quito, Grupo de Química Computacional y Teórica, Diego de Robles sn y Vía Interoceánica, 17-1200-841, Quito, Ecuador.
authors.forename: Daniel
authors.initials: D
authors.lastname: Aguilera-Pesantes
authors.affiliation: Universidad San Francisco de Quito, Instituto de Simulación Computacional (ISC-USFQ), Diego de Robles sn y Vía Interoceánica, 17-1200-841, Quito, Ecuador; Universidad San Francisco de Quito, Grupo de Química Computacional y Teórica, Diego de Robles sn y Vía Interoceánica, 17-1200-841, Quito, Ecuador; Universidad San Francisco de Quito, Escuela de Medicina, Colegio de Ciencias de la Salud (COCSA), Av. Interoceánica Km 12 ½; y Av. Florencia, 17-1200-841, Cumbayá, Quito, Ecuador. Electronic address: mmendez@usfq.edu.ec.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Méndez
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D000072417:Protein Domains; D017386:Sequence Homology, Amino Acid; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D000071244:Zika Virus / Q000201:enzymology*
chemical_list: C080102:NS2B protein, flavivirus; D017361:Viral Nonstructural Proteins
keywords: Computational alanine scanning mutagenesis; Flavivirus; NS2b; NS3; Protein disorder; Transmembrane domains; Zika virus