Exploring NMR ensembles of calcium binding proteins: Perspectives to design inhibitors of protein-protein interactions.
Protein-protein interactions (PPIs) are important for regulating many biological functions. It has been suggested that the human interactome involves about 650,000 interactions and disrupting these interactions could be an attractive way to block a number of targets involved in different pathologies. A possible strategy to inhibit undesired PPIs is
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to design small organic molecules binding in the zone of interactions.Disrupting protein-protein interactions by small organic molecules is nowadays a promising strategy employed to block protein targets involved in different pathologies. However, structural changes occurring at the binding interfaces make difficult drug discovery processes using structure-based drug design/virtual screening approaches.
Here, scientists focused on two homologous calcium binding proteins, calmodulin and human centrin 2, involved in different cellular functions via protein-protein interactions, and known to undergo important conformational changes upon ligand binding. Thier results show that docking on NMR structures of calmodulin and centrin can be very helpful to take into account conformational changes occurring at protein-protein interfaces.
NMR structures of protein-protein complexes nowadays available could efficiently be exploited for further structure-based drug design/virtual screening processes employed to design small molecule inhibitors of protein-protein interactions.
Authors: Adriana Isvoran, Anne Badel, Constantin T Craescu, Simona Miron, and Maria A Miteva.
Source: Isvoran et al. BMC Structural Biology 2011, 11:24
Publication date: 22nd May, 2011.
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