Evaluación computacional de las interacciones de compuestos naturales y el dominio unión al ARN de las nucleolinas utilizando acoplamiento molecular y simulaciones de dinámica molecular

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Gayozo-Melgarejo, E., & Rojas-Aguadé, L. (2023). Evaluación computacional de las interacciones de compuestos naturales y el dominio unión al ARN de las nucleolinas utilizando acoplamiento molecular y simulaciones de dinámica molecular. Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales, 47(183), 385–399. https://doi.org/10.18257/raccefyn.1830


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Varios estudios proponen la nucleolina como un blanco alternativo para la búsqueda y el diseño de nuevas terapias antitumorales o anticancerígenas. El objetivo de este estudio fue evaluar compuestos con potenciales afinidades de unión al ARN de las nucleolinas mediante herramientas bioinformáticas. Se evaluaron diez compuestos de los cuales tres moléculas (ácido betulínico, triptolide y berberina) presentaron afinidades de interacción con el dominio de unión al ARN (RNA binding domain, RBD), exhibiendo valores de energía de unión significativamente favorables (p<0,05) y una constante de disociación calculada (Kd calc) entre 0,14 y 0,91 μM. Las simulaciones de dinámica molecular evidenciaron que únicamente el complejo nucleolina-berberina tuvo estabilidad de interacción y energía libre de unión favorable en el tiempo simulado. Los residuos involucrados en la formación del complejo eran aminoácidos que cumplen funciones importantes en el sitio activo. Los hallazgos sugieren que, entre los compuestos evaluados, la berberina tuvo resultados favorables como potencial inhibidor de las actividades de la nucleolina, específicamente del dominio RBD.


Palabras clave

Bioinformática | Berberina | Cáncer | in silico | Nucleolinas | Productos naturales


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