Presentation description

Disruptions in hormone-receptor interactions underlie a wide range of human diseases, from metabolic and reproductive disorders to cancers and neurological conditions. Hormones are signaling molecules that bind to specific receptor(s) to initiate physiological responses. However, these ligands can also bind to receptors that were previously overlooked, potentially activating the receptor or disrupting its function. To explore such alternative interactions, we employed AlphaFold-Multimer, a cutting-edge AI-based protein structure prediction tool, to systematically evaluate all possible pairwise binding combinations of known hormones and receptors. By ranking interaction scores and reviewing the literature, we identified alternative hormone-receptor pairs based on their prior lack of study. Top candidates were then re-evaluated using a newer prediction tool, AlphaFold3, to assess their binding potential. Based on this secondary screen, we identified at least five candidate alternative hormone-receptor pairs. One represents a neuropeptide known for protecting the brain from damage, which binds to a receptor in the gut, suggesting an unexpected role in digestion. Future directions include testing if the predicted binding alternative hormone-receptor pairs are evolutionarily conserved. This approach aims to uncover novel hormone-receptor interactions that may provide insight into basic biological processes and unexplained genetic diseases.