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


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.

Año de publicación:

2019

Keywords:

  • NS5
  • STAT2
  • molecular dynamics
  • Zika Virus
  • docking

Fuente:

googlegoogle
scopusscopus

Tipo de documento:

Conference Object

Estado:

Acceso restringido

Áreas de conocimiento:

  • Biología molecular
  • Simulación por computadora

Áreas temáticas:

  • Técnicas, equipos y materiales
  • Enfermedades
  • Fisiología humana