Modeling stereospecific drug interactions with beta-adrenergic receptor

Beta-adrenergic receptors (βARs) are G protein-coupled receptors that regulate processes such as heart rhythm and vascular tone by binding agonists like norepinephrine, inducing downstream signaling pathways. Beta blockers antagonize βARs, reducing heart rate and lowering vascular tone. We developed a new Rosetta structural modeling protocol to create state-specific models of β1AR and investigated its atomistic-scale interactions with beta-blocker stereoisomers: d- and l-sotalol, as well as R- and S-propranolol. Our combined molecular dynamics (MD) simulations and docking protocol effectively captured the differences in stereoisomer specificity in binding to β1AR. Binding energetics results favored l-sotalol and S-propranolol, consistent with experimental findings showing d-sotalol has significantly lower affinity for beta-adrenergic receptors than l-sotalol. The entropy term was identified as the primary factor driving enantiomer binding specificity, with higher entropy costs for d-sot..., The input files for structure modeling and MD simulations, output files, and MD simulation trajectories were collected and presented. , , # Data from: Modeling stereospecific drug interactions with beta-adrenergic receptor

The dataset focuses on molecular modeling and simulations of the beta-1 adrenergic receptor interacting with different stereoisomers of the beta-blockers sotalol and propranolol. It includes input files, setup configurations, and key output files used for Rosetta structural modeling, RosettaLigand docking, conventional all-atom molecular dynamics (MD) equilibration and production runs, as well as Gaussian accelerated MD (GaMD) simulations.

Key data files for simulation setup and analysis are included, along with scripts used to perform these analyses. Files with the \".sh\" extension are executable shell scripts that can be run from the command line. Example output files and short MD simulation trajectories are also provided. Users can visualize the trajectories using software such as VMD.

The analyses and results generated from this dataset will be published in peer-reviewed journals, with appropriate...,