Interaction of ZIKV NS5 and STAT2 Explored by Molecular Modeling, Docking, and Simulations Studies

Gerardo Armijos-Capa, Paúl Pozo-Guerrón, F. Javier Torres, Miguel M. Méndez

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

ZIKV NS5 has been associated with inhibition of type I IFN during the host antiviral response. The protein-protein interaction may promote the proteasomal degradation of STAT2, although the entire mechanism is still unknown. In this study, a three-dimensional model of the full STAT2 protein (C-score = - 0.62 ) was validated. Likewise, the top scored docked complex NS5-STAT2 is presented among several other models; the top model shows a total stabilizing energy for the complex of - 77.942 kcal mol - 1 and a Gibbs binding free energy of - 4.30 kcal mol - 1. The analysis of the complex has revealed that the interaction is limited to three domains known as N-terminal from STAT2 and Mtase-Thumb from NS5; both located in the ordered regions of these proteins. Key residues involved in the interaction interface that showed the highest frequency among the models are stabilized by electrostatic interactions, hydrophobic interactions, salt bridges, and ionic interactions. Therefore, our findings support the experimental preliminaries observations reported in the literature and present additional structural characterization that will help in the drug design efforts against ZIKV NS5.

Original languageEnglish (US)
Title of host publicationBioinformatics and Biomedical Engineering - 7th International Work-Conference, IWBBIO 2019, Proceedings
EditorsIgnacio Rojas, Fernando Rojas, Francisco Ortuño, Francisco Ortuño, Olga Valenzuela
PublisherSpringer
Pages165-176
Number of pages12
ISBN (Print)9783030179342
DOIs
StatePublished - 2019
Externally publishedYes
Event7th International Work-Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2019 - Granada, Spain
Duration: May 8 2019May 10 2019

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume11466 LNBI
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Conference

Conference7th International Work-Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2019
Country/TerritorySpain
CityGranada
Period5/8/195/10/19

All Science Journal Classification (ASJC) codes

  • Theoretical Computer Science
  • Computer Science(all)

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