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El lanosterol interrumpe la agregación de la γD-cristalina humana al unirse a la interfaz de dimerización hidrofóbica

Hongsuk Kang^1,2, Zaixing Yang³, Ruhong Zhou^1,2

¹Institute of Quantitative Biology, Department of Physics , Zhejiang University , Hangzhou 310027 , China.

Journal of the American Chemical Society

|June 20, 2018

Resumen

El lanosterol previene y revierte la formación de cataratas al unirse a las cristalinas gamma D humanas. Este compuesto esteroide muestra una fuerte afinidad por sitios específicos, inhibiendo la agregación de proteínas y el deterioro de la visión.

Área de la Ciencia:

La bioquímica
Oftalmología
Biología computacional

Sus antecedentes:

Las cataratas son una causa importante de pérdida de visión, resultante del mal plegamiento y agregación de proteínas cristalinas en el cristalino.
Los mecanismos precisos que impulsan la agregación de cristalina en las cataratas no se comprenden completamente.
El lanosterol, un esteroide natural, ha demostrado su potencial para prevenir y revertir la formación de cataratas.

Objetivo del estudio:

Investigar los efectos preventivos del lanosterol en la agregación de las gamma-D-cristalinas humanas (HγD-Crys).
Para dilucidar las interacciones moleculares entre el lanosterol y HγD-Crys utilizando métodos computacionales.

Principales métodos:

Simulaciones de dinámica molecular de todos los átomos.
Cálculos de la perturbación de energía libre (FEP).
Transformaciones alquímicas para hacer comparaciones de energía libre.

Principales resultados:

El lanosterol se une preferentemente a la interfaz de dimerización hidrofóbica de HγD-Crys, en particular al extremo C.
El lanosterol exhibe una afinidad de unión más fuerte con HγD-Crys que con su propia autoagregación.
La unión del lanosterol es más favorable que la del colesterol, lo que sugiere una correlación entre la geometría molecular de los esteroides y la afinidad de unión.

Conclusiones:

El lanosterol inhibe eficazmente la agregación de HγD-Crys a través de interacciones de unión específicas.
Los hallazgos apoyan el potencial terapéutico del lanosterol para el tratamiento de la catarata.
La estructura molecular de los esteroides influye en su eficacia para prevenir la agregación cristalina.

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