Virtual Screening of Positive Allosteric Modulators (PAMs) With High Resolution Computational Docking
Our technology is based on the use of cutting-edge tools, including the use of cryo-electron microscopy (cryo-EM) to provide high-resolution three-dimensional structures of our target GPCRs, with particular attention to allosteric pockets that provide opportunities for drug selectivity, such as M4-specific receptor ago-PAM activity – or multi-receptor efficacy, based on our discovery of a highly conserved allosteric site in GLP-1, GIP, glucagon, and amylin receptors.
High resolution docking of a small molecule into the allosteric pocket of the muscarinic M4 receptor
(2.4 Angstrom)
Positive Allosteric Modulators (PAMs)
Compared to traditional exogenous orthosteric agonists, PAMs have the advantage of acting at a separate site to conserve the natural signaling pattern of the endogenous orthosteric agonist. In cases where baseline natural signaling is too low, ago-PAMs that also possess intrinsic agonism can be used to recreate background “tone” while still enabling amplification of natural signaling. Oban’s technology is designed to efficiently exploit the novel opportunities for therapeutic advantages provided by allosteric modulation of GPCRs.