TY - GEN
T1 - Interaction of ZIKV NS5 and STAT2 Explored by Molecular Modeling, Docking, and Simulations Studies
AU - Armijos-Capa, Gerardo
AU - Pozo-Guerrón, Paúl
AU - Torres, F. Javier
AU - Méndez, Miguel M.
N1 - Funding Information:
Supported by Universidad San Francisco de Quito.
Publisher Copyright:
© 2019, Springer Nature Switzerland AG.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1007/978-3-030-17935-9_16
DO - 10.1007/978-3-030-17935-9_16
M3 - Conference contribution
AN - SCOPUS:85065723527
SN - 9783030179342
T3 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
SP - 165
EP - 176
BT - Bioinformatics and Biomedical Engineering - 7th International Work-Conference, IWBBIO 2019, Proceedings
A2 - Rojas, Ignacio
A2 - Rojas, Fernando
A2 - Ortuño, Francisco
A2 - Ortuño, Francisco
A2 - Valenzuela, Olga
PB - Springer
T2 - 7th International Work-Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2019
Y2 - 8 May 2019 through 10 May 2019
ER -
