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A unifying motif of intermolecular cooperativity in protein associations

  • S. R. Accordino
  • J. A. Rodriguez Fris
  • G. A. AppignanesiEmail author
  • A. Fernández
Regular Article

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.

Keywords

Soft Matter: Interfacial Phenomena and Nanostructured Surfaces 

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Copyright information

© EDP Sciences, SIF, Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • S. R. Accordino
    • 1
  • J. A. Rodriguez Fris
    • 1
  • G. A. Appignanesi
    • 1
    Email author
  • A. Fernández
    • 2
  1. 1.Sección Fisicoquímica, INQUISUR-UNS-CONICET-Departamento de QuímicaUniversidad Nacional del SurBahía BlancaArgentina
  2. 2.Instituto Argentino de Matemática “Alberto P. Calderón”Buenos AiresArgentina

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