Investigating the Unbinding of Muscarinic Antagonists from the Muscarinic 3 Receptor.

ABSTRACT: Patient symptom relief is often heavily influenced by the residence time of the inhibitor-target complex. For the human muscarinic receptor 3 (hMR3), tiotropium is a long-acting bronchodilator used in conditions such as asthma or chronic obstructive pulmonary disease (COPD). The mechanistic insights into this inhibitor remain unclear; specifically, the elucidation of the main factors determining the unbinding rates could help develop the next generation of antimuscarinic agents. Using our novel unbinding algorithm, we were able to investigate ligand dissociation from hMR3. The unbinding paths of tiotropium and two of its analogues, N-methylscopolamin and homatropine methylbromide, show a consistent qualitative mechanism and allow us to identify the structural bottleneck of the proce

SUBMITTER: Buigues PJ 

PROVIDER: S-EPMC10413856 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature