6533b86dfe1ef96bd12c9508

RESEARCH PRODUCT

Mapping molecular binding by means of conformational dynamics measurements

Augusto Juste-dolzPaulo Roberto BuenoIsidro S. MonzóSergi MoraisÁNgel MaquieiraDavid Giménez-romeroJosé Luis López-pazRoberto TejeroNoelle M. Do Nascimento

subject

0301 basic medicinePhysicsDrug discoveryMechanism (biology)General Chemical EngineeringDynamics (mechanics)Molecular bindingGeneral ChemistryQuartz crystal microbalance03 medical and health sciences030104 developmental biologyDual-polarization interferometryQUIMICA ANALITICABiological system

description

[EN] Protein-protein interactions are key in virtually all biological processes. The study of these interactions and the interfaces that mediate them play a key role in the understanding of biological function. In particular, the observation of protein¿protein interactions in their dynamic environment is technically difficult. Here two surface analysis techniques, dual polarization interferometry and quartz crystal microbalance with dissipation monitoring, were paired for real-time mapping of the conformational dynamics of protein¿ protein interactions. Our approach monitors this dynamics in real time and in situ, which is a great advancement within technological platforms for drug discovery. Results agree with the experimental observations of the interaction between the TRIM21a protein and circulating autoantibodies via a bridging bipolar mechanism. This work provides a new chip-based method to monitor conformational dynamics of protein¿protein interactions, which is amenable to miniaturized high-throughput determination.

https://doi.org/10.1039/c7ra10617c