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

Gerardo Armijos-Capa; Pa&#x00FA;l Pozo-Guerr&#x00F3;n; F. Javier Torres; Miguel M. M&#x00E9;ndez

doi:10.1007/978-3-030-17935-9_16

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/Inform › Conference 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-scoreÂ = - 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 kcalÂ mol ^{- 1} and a Gibbs binding free energy of - 4.30 kcalÂ 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 language	English (US)
Title of host publication	Bioinformatics and Biomedical Engineering - 7th International Work-Conference, IWBBIO 2019, Proceedings
Editors	Ignacio Rojas, Fernando Rojas, Francisco Ortuño, Francisco Ortuño, Olga Valenzuela
Publisher	Springer
Pages	165-176
Number of pages	12
ISBN (Print)	9783030179342
DOIs	https://doi.org/10.1007/978-3-030-17935-9_16
State	Published - 2019
Externally published	Yes
Event	7th International Work-Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2019 - Granada, Spain Duration: May 8 2019 → May 10 2019

Publication series

Name	Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume	11466 LNBI
ISSN (Print)	0302-9743
ISSN (Electronic)	1611-3349

Conference

Conference	7th International Work-Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2019
Country/Territory	Spain
City	Granada
Period	5/8/19 → 5/10/19

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

Theoretical Computer Science
General Computer Science

Access to Document

10.1007/978-3-030-17935-9_16

Cite this

Armijos-Capa, G., Pozo-Guerrón, PFA., Torres, F. J., & Méndez, M. M. (2019). Interaction of ZIKV NS5 and STAT2 Explored by Molecular Modeling, Docking, and Simulations Studies. In I. Rojas, F. Rojas, F. Ortuño, F. Ortuño, & O. Valenzuela (Eds.), Bioinformatics and Biomedical Engineering - 7th International Work-Conference, IWBBIO 2019, Proceedings (pp. 165-176). (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 11466 LNBI). Springer. https://doi.org/10.1007/978-3-030-17935-9_16

Armijos-Capa, Gerardo ; Pozo-Guerrón, Paúl ; Torres, F. Javier et al. / Interaction of ZIKV NS5 and STAT2 Explored by Molecular Modeling, Docking, and Simulations Studies. Bioinformatics and Biomedical Engineering - 7th International Work-Conference, IWBBIO 2019, Proceedings. editor / Ignacio Rojas ; Fernando Rojas ; Francisco Ortuño ; Francisco Ortuño ; Olga Valenzuela. Springer, 2019. pp. 165-176 (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)).

@inproceedings{6565fee895684af299ea404da8904a69,

title = "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{\^A} = - 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{\^A} mol - 1 and a Gibbs binding free energy of - 4.30 kcal{\^A} 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.",

author = "Gerardo Armijos-Capa and Pa\&\#x00FA;l Pozo-Guerr\&\#x00F3;n and Torres, \{F. Javier\} and M\&\#x00E9;ndez, \{Miguel M.\}",

note = "Funding Information: Supported by Universidad San Francisco de Quito. Publisher Copyright: \&\#x00A9; 2019, Springer Nature Switzerland AG.; 7th International Work-Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2019 ; Conference date: 08-05-2019 Through 10-05-2019",

year = "2019",

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publisher = "Springer",

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editor = "Ignacio Rojas and Fernando Rojas and Francisco Ortu{\~n}o and Francisco Ortu{\~n}o and Olga Valenzuela",

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Armijos-Capa, G, Pozo-Guerrón, PFA, Torres, FJ & Méndez, MM 2019, Interaction of ZIKV NS5 and STAT2 Explored by Molecular Modeling, Docking, and Simulations Studies. in I Rojas, F Rojas, F Ortuño, F Ortuño & O Valenzuela (eds), Bioinformatics and Biomedical Engineering - 7th International Work-Conference, IWBBIO 2019, Proceedings. Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), vol. 11466 LNBI, Springer, pp. 165-176, 7th International Work-Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2019, Granada, Spain, 5/8/19. https://doi.org/10.1007/978-3-030-17935-9_16

Interaction of ZIKV NS5 and STAT2 Explored by Molecular Modeling, Docking, and Simulations Studies. / Armijos-Capa, Gerardo; Pozo-Guerrón, Paúl; Torres, F. Javier et al.
Bioinformatics and Biomedical Engineering - 7th International Work-Conference, IWBBIO 2019, Proceedings. ed. / Ignacio Rojas; Fernando Rojas; Francisco Ortuño; Francisco Ortuño; Olga Valenzuela. Springer, 2019. p. 165-176 (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 11466 LNBI).

Research output: Chapter in Book/Inform › Conference contribution

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.

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-scoreÂ = - 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 kcalÂ mol - 1 and a Gibbs binding free energy of - 4.30 kcalÂ 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-scoreÂ = - 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 kcalÂ mol - 1 and a Gibbs binding free energy of - 4.30 kcalÂ 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.

UR - https://www.scopus.com/pages/publications/85065723527

UR - https://www.scopus.com/pages/publications/85065723527#tab=citedBy

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 - 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 -

Armijos-Capa G, Pozo-Guerrón PFA, Torres FJ, Méndez MM. Interaction of ZIKV NS5 and STAT2 Explored by Molecular Modeling, Docking, and Simulations Studies. In Rojas I, Rojas F, Ortuño F, Ortuño F, Valenzuela O, editors, Bioinformatics and Biomedical Engineering - 7th International Work-Conference, IWBBIO 2019, Proceedings. Springer. 2019. p. 165-176. (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)). doi: 10.1007/978-3-030-17935-9_16

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

Abstract

Publication series

Conference

UN SDGs

All Science Journal Classification (ASJC) codes

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