Artículo
Non-Debye frustrated hydration steers biomolecular association: interfacial tension for the drug designer
Fecha de publicación:
10/2016
Editorial:
Wiley
Revista:
FEBS Letters
ISSN:
0014-5793
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Many cellular functions involve the assembly of biomolecular complexes, a process mediated by water that gets displaced as subunits bind. This process affects water frustration, that is, the number of unmet hydrogen-bonding opportunities at the protein–water interface. By searching for least-frustrated aqueous interfaces, this study delineates the role of frustration in steering molecular assemblage. The search entails a trajectory sampling using a functional that measures the gradient of frustration and computing the resulting non-Debye electrostatics within relaxation times for coupled protein–water systems. The minimal frustration principle is validated against spectroscopic measurements of frustration-dependent dielectric relaxation, affinity scanning of protein–protein interfaces, and NMR-inferred association propensities of protein-complex intermediates. The methods are applied to drug design, revealing the targetable nature of the aqueous interface.
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Articulos(IAM)
Articulos de INST.ARG.DE MATEMATICAS "ALBERTO CALDERON"
Articulos de INST.ARG.DE MATEMATICAS "ALBERTO CALDERON"
Citación
Fernandez, Ariel; Non-Debye frustrated hydration steers biomolecular association: interfacial tension for the drug designer; Wiley; FEBS Letters; 590; 20; 10-2016; 3481-3491
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