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Naturaleza de las interacciones carbonyl-carbonyl amida en las proteínas
Amit Choudhary1, Deepa Gandla, Grant R Krow
1Graduate Program in Biophysics, University of Wisconsin, Madison, Wisconsin 53706, USA.
Journal of the American Chemical Society
|May 28, 2009
Resumen
La interacción entre grupos carbonilo adyacentes en las proteínas se debe principalmente a la deslocalización electrónica, no a las interacciones de carga. Este hallazgo impacta nuestra comprensión de la estructura e interacciones biomoleculares.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
- Química computacional es la química computacional.
Sus antecedentes:
- Las interacciones no covalentes son fundamentales para la estructura, función y dinámica biomolecular.
- Los grupos carbonilo adyacentes en las estructuras secundarias de proteínas exhiben una interacción íntima crucial para la estabilidad y la unión de ligandos.
Objetivo del estudio:
- Aclarar el origen primario de la interacción íntima entre grupos carbonilo adyacentes en enlaces péptidos.
- Para diferenciar entre carga-carga, dipolo-dipolo, y n-->pi* deslocalización electrónica como la causa de esta interacción.
Principales métodos:
- Utilizó un sistema de modelo peptídico con sustitutos químicos isostéricos.
- Se empleó la espectroscopia de Resonancia Magnética Nuclear (RMN) para el análisis.
- Se realizó un análisis de difracción de rayos X.
- Realizó cálculos químicos cuánticos desde el principio.
Principales resultados:
- Se demostró que la interacción íntima entre grupos carbonilo adyacentes surge predominantemente de la deslocalización electrónica n-->pi*.
- Esta deslocalización electrónica implica pares solitarios en el oxígeno de un enlace péptido que interactúa con el orbital antienlace del grupo carbonilo adyacente.
- Se descartaron las interacciones carga-carga o dipolo-dipolo como los principales contribuyentes.
Conclusiones:
- La deslocalización electrónica n->pi* es el principal impulsor del contacto cercano entre carbonilos adyacentes en las proteínas.
- Esta comprensión tiene implicaciones significativas para la química orgánica, la bioquímica y la química medicinal.
- Proporciona información sobre las contribuciones energéticas a la estabilidad conformacional de las proteínas y las interacciones proteína-ligando.
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