"With this tool we have a way to go deeper and really experimentally probe ideas about molecular heterogeneity and molecular aging," senior author Laurent Limozin, biophysicist at the Centre National de la Recherche Scientifique, said in a statement. They believe that testing the same protein-protein bond multiple times may help in exploring variation between molecularly identical pairs, and in examining how these interactions change as the molecules age, which could be important for determining the half-life of drugs or antibodies. The researchers observed these cycles of bonding and rupturing under a microscope. Without this leash, the detachment would be irreversible.Īs a proof of concept, the research team used the technique to characterize two single-molecule interactions of biomedical interest: the bond between proteins and rapamycin, an immunosuppressive drug, and the bond between a single-domain antibody and an HIV-1 antigen. This strand acts as the leash keeping the two proteins close together after their bond is ruptured. Whether using your bioceramic or DSMs proprietary bioceramics, we provide partners with custom collagen-based scaffolds for enhanced bone healing. This method also incorporates a third strand of DNA between the two side strands. If the force is strong enough, this pull ruptures the bond between the two proteins.
When the researchers blast the chamber with a soundwave, the wave's force pulls the silicon bead - and the protein attached to it - away from the bottom of the chamber. The DNA scaffolding involves one strand of DNA that attaches the first protein to the bottom of the chamber, while another strand attaches the second protein to a small silica bead. This innovation allows the same protein bonds to be re-tested up to 100 times, providing valuable information about how bond strength changes as molecules age.ĭuring acoustic force spectroscopy, the bonded protein pairs are tested inside a liquid-filled chamber. While the DNA scaffold holds the two proteins together, their bond is characterized using acoustic force spectroscopy. Their method used sound waves to pull two bonded proteins apart and DNA "leashes" to keep the proteins close together so that they could re-bond after their connection was ruptured. They combined two existing technologies: acoustic force spectroscopy, which allows many molecular pairs to be tested simultaneously, and DNA scaffolds, which enable the same bonds to be tested repeatedly. The researchers sought to develop a method with high molecular precision and throughput that could be applied to different types of bonds. Here, we describe deep learning approaches for scaffolding such functional sites without needing to prespecify the fold or secondary structure of the scaffold. However, current testing methods are limited in their ability to provide information at the single bond level, or to test large numbers of bonds. The binding and catalytic functions of proteins are generally mediated by a small number of functional residues held in place by the overall protein structure. Accurate characterization of protein-protein bonds is important for testing the performance of potential therapies.
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