Protein structure defines function. Modern efforts to develop selective and potent therapies seek to improve human health by perturbing protein conformation. Thus, measuring ligand-induced conformational change earlier in the screening process holds promise to finding better drugs faster. He we present the typical drug discovery workflow involved when using the Biodesy Delta as a screening tool.Download
The Biodesy Delta is an easy-to-use, high-throughput system that automates measurement of protein conformational change. It is being used to study a wide range of proteins, regardless of mass or structure, and a wide range of interactions, including fragments, small molecules, antibodies and protein complexes.Download
Many potent and selective drugs induce or stabilize distinct target conformations that improve human health. Novel, innovative and higher throughput technologies that reveal this valuable structural information are needed to enable better decisions earlier in the drug discovery process, accelerating discovery-to-market timelines.
The Biodesy Delta employs second harmonic generation (SHG) technology to measure conformational change at high throughput, enabling a more immediate understanding of the mechanistic and functional consequences of ligand binding. The conformational signatures revealed by the Delta enable discrimination of activators from inhibitors and allosteric from orthosteric interactions, even for the most challenging targets.Download
Proteins are structurally dynamic molecules that perform specialized functions through unique conformational changes accessible in physiological environments. An ability to specifically and selectively control protein function via conformational modulation is an important goal for development of novel therapeutics and studies of protein mechanism in biological networks and disease. Here we applied a second-harmonic generation-based technique for studying protein conformation in solution and in real time to the intrinsically disordered, Parkinson disease related protein α-synuclein.Download
Proteins are dynamic molecules that perform specialized functions through unique conformational changes accessible in physiological environments. An ability to specifically and selectively control protein function via conformational modulation is an important goal for development of novel therapeutics and studies of protein functions in biological networks. Current structural techniques are limited in their ability to probe conformational changes in many proteins and in solution. To bridge this gap, we developed an SHG-based technique and applied it to three different protein models: calmodulin, maltose-binding protein, and dihydrofolate reductase.Download
Peripheral membrane proteins are key regulators of signal transduction pathways at cell membranes. These signaling pathways are activated by conformational changes that occur in peripheral membrane proteins upon ligand binding. Currently, the ability to measure ligand induced conformational change in peripheral membrane proteins under physi- ological conditions is difficult. Here, we discuss a novel approach for detecting and measuring conformational change in peripheral membrane proteins when attached directly to physiologically relevant supported lipid bilayers.Download