Dynamic pharmacophores unveil binding mode ensembles for classical partial agonists at the M2 receptor
Wunsch, F.; Kauk, M.; Filor, J.; Wolber, G.; Holzgrabe, U.; Hoffmann, C.; Bermudez, M.
Show abstract
For the prototypic M2 receptor it has been previously demonstrated that dualsteric partial agonists can stabilize both, active and inactive receptor states, but it remains unclear whether orthosteric partial agonists have a similar mechanism. Here, we apply dynamic pharmacophores to unveil binding mode ensembles for classical M2 partial agonists. We report correlations between the spatial distribution of lipophilic contacts and ligand efficacy and demonstrate the applicability of dynamic pharmacophores to analyze subtle binding mode changes.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Energetics of a protein disorder-order transition in small molecule recognition 94%
- Transfer learning enables discovery of sub-micromolar antibacterials for ESKAPE pathogens from ultra-large chemical spaces 94%
- Discovery of small-molecule inhibitors targeting the ribosomal peptidyl transferase center (PTC) of M. tuberculosis 93%
Similar papers in this journal
- From atoms to cells: bridging the gap between potency, efficacy, and safety of small molecules directed at a membrane protein 94%
- Pharmacological Characterisation of Novel Adenosine Receptor A3R Antagonists 92%
- HTRF-based identification of small molecules targeting SARS-CoV-2 E protein interaction with ZO-1 PDZ2 92%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.