Análisis estructural de interacciones in silico de fitoconstituyentes de Solanum americanum, Solanum guaraniticum y Solanum lycopersicum con la proteína tripanotiona reductasa de Leishmania infantum
Leishmania infantum is the main cause of visceral leishmaniasis in humans and several other mammals. Numerous studies suggest that trypanothione reductase (TR) is a good target to search for bioactive molecules capable of interacting and inhibiting functions of this protein. The objective of this research was to determine in silico phytoconstituents from Solanum americanum, Solanum guaraniticum and Solanum lycopersicum that show interaction affinities to TR, by analysis of molecular docking and molecular dynamics simulations. A total of thirty molecules described in S. americanum, S. guaraniticum, and S. lycopersicum were evaluated. Molecular docking tests were performed between these molecules and TR’s active site. All molecules demonstratedinteraction affinities to TR; however, the ones which showed significantly favorable interaction energy values (p<0.001) were solasodine, solamargine, and manghaslin. Subsequently, the analysis of molecular dynamics simulations revealed that only the interaction with solasodine proved to be stable and present significantly favorable interaction-free energy (ΔGu = -4.68±2.57 kcal.mol-1; p<0.05); however, interactions with solamargine and manghaslin were unfavorable (ΔGu = 0.87±0.19 kcal.mol-1 and ΔGu = 12.79±9.25 kcal.mol-1 respectively). The active residues of TR involved in the interaction with solasodine were Lys60, Tyr198 and Arg287. These findings suggest that the TR protein could be an interaction target for the glycoalkaloid solasodine , and could be a potential inhibitor of its enzymatic activity.
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Facultad de Ciencias Exactas y Naturales - Universidad Nacional de Asunción
2022
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rev-steviana-py-article22172022-06-29T11:06:40Z Análisis estructural de interacciones in silico de fitoconstituyentes de Solanum americanum, Solanum guaraniticum y Solanum lycopersicum con la proteína tripanotiona reductasa de Leishmania infantum Gayozo, E. Rojas, L. Leishmania infantum is the main cause of visceral leishmaniasis in humans and several other mammals. Numerous studies suggest that trypanothione reductase (TR) is a good target to search for bioactive molecules capable of interacting and inhibiting functions of this protein. The objective of this research was to determine in silico phytoconstituents from Solanum americanum, Solanum guaraniticum and Solanum lycopersicum that show interaction affinities to TR, by analysis of molecular docking and molecular dynamics simulations. A total of thirty molecules described in S. americanum, S. guaraniticum, and S. lycopersicum were evaluated. Molecular docking tests were performed between these molecules and TR’s active site. All molecules demonstratedinteraction affinities to TR; however, the ones which showed significantly favorable interaction energy values (p<0.001) were solasodine, solamargine, and manghaslin. Subsequently, the analysis of molecular dynamics simulations revealed that only the interaction with solasodine proved to be stable and present significantly favorable interaction-free energy (ΔGu = -4.68±2.57 kcal.mol-1; p<0.05); however, interactions with solamargine and manghaslin were unfavorable (ΔGu = 0.87±0.19 kcal.mol-1 and ΔGu = 12.79±9.25 kcal.mol-1 respectively). The active residues of TR involved in the interaction with solasodine were Lys60, Tyr198 and Arg287. These findings suggest that the TR protein could be an interaction target for the glycoalkaloid solasodine , and could be a potential inhibitor of its enzymatic activity. Leishmania infantum es el principal causante de leishmaniasis visceral en humanos y en varios mamíferos. Numerosos estudios sugieren que la tripanotiona reductasa (TR) es un buen blanco para la búsqueda de moléculas bioactivas capaces de interaccionar e inhibir funciones de esta proteína. El objetivo de esta investigación fue determinar in silico los fitoconstituyentes de S. americanum, S. guaraniticum y S. lycopersicum que demuestran afinidades de interacción con la TR, mediante el análisis de acoplamientos moleculares y simulaciones de dinámica molecular. Se evaluaron un total de treinta moléculas descritas en Solanum americanum, Solanum guaraniticum y Solanum lycopersicum. Las pruebas de acoplamiento molecular se realizaron entre estas y el sitio activo de la TR. Todas las moléculas demostraron afinidades de interacción por la TR, sin embargo, las que presentaron valores de energía de interacción significativamente favorables (p<0,001) entre todas fueron la solasodina, la solamargina y la manghaslina. Posteriormente, el análisis de las simulaciones de dinámica molecular reveló que solo la interacción con la solasodina demostró ser estable y presentar energía libre de interacción significativamente favorable (ΔGu = -4,68±2,57 kcal.mol-1; p<0,05), sin embargo, las interacciones con la solamargina y la manghaslina resultaron desfavorables (ΔGu = 0,87±0,19 kcal. mol-1 y ΔGu = 12,79±9,25 kcal.mol-1 respectivamente). Los residuos activos de la TR implicados en la interacción con la solasodina fueron la Lys60, la Tyr198 y la Arg287. Estos hallazgos sugieren que la proteína TR podría ser un blanco de interacción del glicoalcaloide solasodina, pudiendo ser un potencial inhibidor de su actividad enzimática. Facultad de Ciencias Exactas y Naturales - Universidad Nacional de Asunción 2022-02-02 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion artículo evaluado por pares application/pdf https://revistascientificas.una.py/index.php/stevia/article/view/2217 10.56152/StevianaFacenV12N2A2_2020 Steviana ; Vol. 12 Núm. 2 (2020): Steviana; 31-54 2077-8430 2304-2907 10.56152/StevianaFacenV12N2_2020 spa https://revistascientificas.una.py/index.php/stevia/article/view/2217/2084 |
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| author |
Gayozo, E. Rojas, L. |
| spellingShingle |
Gayozo, E. Rojas, L. Análisis estructural de interacciones in silico de fitoconstituyentes de Solanum americanum, Solanum guaraniticum y Solanum lycopersicum con la proteína tripanotiona reductasa de Leishmania infantum |
| author_facet |
Gayozo, E. Rojas, L. |
| author_sort |
Gayozo, E. |
| title |
Análisis estructural de interacciones in silico de fitoconstituyentes de Solanum americanum, Solanum guaraniticum y Solanum lycopersicum con la proteína tripanotiona reductasa de Leishmania infantum |
| title_short |
Análisis estructural de interacciones in silico de fitoconstituyentes de Solanum americanum, Solanum guaraniticum y Solanum lycopersicum con la proteína tripanotiona reductasa de Leishmania infantum |
| title_full |
Análisis estructural de interacciones in silico de fitoconstituyentes de Solanum americanum, Solanum guaraniticum y Solanum lycopersicum con la proteína tripanotiona reductasa de Leishmania infantum |
| title_fullStr |
Análisis estructural de interacciones in silico de fitoconstituyentes de Solanum americanum, Solanum guaraniticum y Solanum lycopersicum con la proteína tripanotiona reductasa de Leishmania infantum |
| title_full_unstemmed |
Análisis estructural de interacciones in silico de fitoconstituyentes de Solanum americanum, Solanum guaraniticum y Solanum lycopersicum con la proteína tripanotiona reductasa de Leishmania infantum |
| title_sort |
análisis estructural de interacciones in silico de fitoconstituyentes de solanum americanum, solanum guaraniticum y solanum lycopersicum con la proteína tripanotiona reductasa de leishmania infantum |
| description |
Leishmania infantum is the main cause of visceral leishmaniasis in humans and several other mammals. Numerous studies suggest that trypanothione reductase (TR) is a good target to search for bioactive molecules capable of interacting and inhibiting functions of this protein. The objective of this research was to determine in silico phytoconstituents from Solanum americanum, Solanum guaraniticum and Solanum lycopersicum that show interaction affinities to TR, by analysis of molecular docking and molecular dynamics simulations. A total of thirty molecules described in S. americanum, S. guaraniticum, and S. lycopersicum were evaluated. Molecular docking tests were performed between these molecules and TR’s active site. All molecules demonstratedinteraction affinities to TR; however, the ones which showed significantly favorable interaction energy values (p<0.001) were solasodine, solamargine, and manghaslin. Subsequently, the analysis of molecular dynamics simulations revealed that only the interaction with solasodine proved to be stable and present significantly favorable interaction-free energy (ΔGu = -4.68±2.57 kcal.mol-1; p<0.05); however, interactions with solamargine and manghaslin were unfavorable (ΔGu = 0.87±0.19 kcal.mol-1 and ΔGu = 12.79±9.25 kcal.mol-1 respectively). The active residues of TR involved in the interaction with solasodine were Lys60, Tyr198 and Arg287. These findings suggest that the TR protein could be an interaction target for the glycoalkaloid solasodine , and could be a potential inhibitor of its enzymatic activity. |
| publisher |
Facultad de Ciencias Exactas y Naturales - Universidad Nacional de Asunción |
| publishDate |
2022 |
| url |
https://revistascientificas.una.py/index.php/stevia/article/view/2217 |
| work_keys_str_mv |
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| _version_ |
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