Eur. Phys. J. E (2012) 35: 59
https://doi.org/10.1140/epje/i2012-12059-0

Regular Article

A unifying motif of intermolecular cooperativity in protein associations

¹ Sección Fisicoquímica, INQUISUR-UNS-CONICET-Departamento de Química, Universidad Nacional del Sur, Avda. Alem 1253, 8000, Bahía Blanca, Argentina
² Instituto Argentino de Matemática “Alberto P. Calderón”, CONICET, 1083, Buenos Aires, Argentina

^* e-mail: appignan@criba.edu.ar

Received: 5 April 2012
Revised: 25 May 2012
Accepted: 15 June 2012
Published online: 16 July 2012

Abstract

At the molecular level, most biological processes entail protein associations which in turn rely on a small fraction of interfacial residues called hot spots. Our theoretical analysis shows that hot spots share a unifying molecular attribute: they provide a third-body contribution to intermolecular cooperativity. Such motif, based on the wrapping of interfacial electrostatic interactions, is essential to maintain the integrity of the interface. Thus, our main result is to unravel the molecular nature of the protein association problem by revealing its underlying physics and thus by casting it in simple physical grounds. Such knowledge could then be exploited in rational drug design since the regions here indicated may serve as blueprints to engineer small molecules disruptive of protein-protein interfaces.