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

Producción científica: Capítulo en Libro/Reporte › Contribución a la conferencia

Resumen

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.

Idioma original	Inglés estadounidense
Título de la publicación alojada	Bioinformatics and Biomedical Engineering - 7th International Work-Conference, IWBBIO 2019, Proceedings
Editores	Ignacio Rojas, Fernando Rojas, Francisco Ortuño, Francisco Ortuño, Olga Valenzuela
Editorial	Springer
Páginas	165-176
Número de páginas	12
ISBN (versión impresa)	9783030179342
DOI	https://doi.org/10.1007/978-3-030-17935-9_16
Estado	Publicada - 2019
Publicado de forma externa	Sí
Evento	7th International Work-Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2019 - Granada, Espana Duración: may. 8 2019 → may. 10 2019

Serie de la publicación

Nombre	Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volumen	11466 LNBI
ISSN (versión impresa)	0302-9743
ISSN (versión digital)	1611-3349

Conferencia

Conferencia	7th International Work-Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2019
País/Territorio	Espana
Ciudad	Granada
Período	5/8/19 → 5/10/19

Áreas temáticas de ASJC Scopus

Ciencia computacional teórica
Ciencia de la Computación General

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

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

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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. En 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)).

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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 Paúl Pozo-Guerrón and Torres, {F. Javier} and Méndez, {Miguel M.}",

note = "Funding Information: Supported by Universidad San Francisco de Quito. Publisher Copyright: © 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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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. En 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, Espana, 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).

Producción científica: Capítulo en Libro/Reporte › Contribución a la conferencia

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.

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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

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A2 - Ortuño, Francisco

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PB - Springer

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Y2 - 8 May 2019 through 10 May 2019

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Armijos-Capa G, Pozo-Guerrón PFA, Torres FJ, Méndez MM. Interaction of ZIKV NS5 and STAT2 Explored by Molecular Modeling, Docking, and Simulations Studies. En Rojas I, Rojas F, Ortuño F, Ortuño F, Valenzuela O, editores, 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

Resumen

Serie de la publicación

Conferencia

Áreas temáticas de ASJC Scopus

ODS de las Naciones Unidas

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