Accordino S R, Rodriguez Fris J A, Appignanesi G A, Fernández A
Sección Fisicoquímica, INQUISUR-UNS-CONICET-Departamento de Química, Universidad Nacional del Sur, Bahía Blanca, Argentina.
Eur Phys J E Soft Matter. 2012 Jul;35(7):59. doi: 10.1140/epje/i2012-12059-0. Epub 2012 Jul 16.
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.
在分子水平上，大多数生物过程都涉及蛋白质结合，而这又依赖于一小部分被称为热点的界面残基。我们的理论分析表明，热点具有一个统一的分子属性：它们为分子间协同作用提供三体贡献。这种基于界面静电相互作用包裹的基序对于维持界面的完整性至关重要。因此，我们的主要成果是通过揭示蛋白质结合问题背后的物理原理，并将其置于简单的物理基础上，从而揭示该问题的分子本质。由于这里指出的区域可作为设计破坏蛋白质 - 蛋白质界面的小分子的蓝图，因此这些知识可用于合理的药物设计。
