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 links provided to this dataset.

Description of the data and file structure

Dataset ICL3_modeling.zip (model preparation for intracellular loop 3 (ICL3))

|- submit_MEF_kic_with_frags_icl3.atomate_jrdd.qsub (ICL3 loop building SLURM job submission script)
|- 7bvq_template_ptrd.pdb (input pdb for ICL3 building, but this one without ICL3, only the helices)
|- 7bu6_template_ptd_dummy_loop.pdb (input pdb for extracting dummy ICL3)
|- 7bvq_template_ptd_dummy_loop.pdb (loop building input pdb with a dummy ICL3, the modeling protocol required coordinates for the loop already be present)
|- adding_dummy_loop.py (Python code to add dummy ICL3 to 7bvq_template_ptrd.pdb)
|- modeling_stages_b1arr_versus_b1ara_2024_resave.py (Miscellaneous Python code)
|- loopmodel_inp (Input files for Rosetta loop modeling)
|| - icl3.loop (Miscellaneous file for loop building)
|| - hb1arr_target.span ( File indicating location of lipid membrane for target protein)
|| - hb1arr_target.fasta (Protein sequence file in the FASTA format )
|| - disulfides.ss (File indicating disulfife bridge location)
|| - ab_inito.map (map file for loop building defining region of protein to be completely rebuilt)
|| - 7bvq_template_ptd_dummy_loop.span (File indicating location of lipid membrane for the template protein)
|| - 7bvq_template_ptd_dummy_loop.pdb (loop building input pdb with a dummy ICL3, the modeling protocol required coordinates for the loop already be present)
|| - hb1arr_target-grishn.aln (Protein sequence alignment file)
|- hb1arr.200.03.3mers (Protein 3-residue fragments used for loop building)
|- hb1arr.200.09.9mers ( Protein 9-residue fragments used for loop building)
|- kic_with_frags_mef.xml (Please refer to the one in Dataset

C_terminal_modeling.zip. Rosetta script in the XML format for KIC loop building with fragments)

|- stage1_membrane.wts (Membrane weights for stage 1 of loop building)
|- stage2_membrane.wts (Membrane weights for stage 2 of loop building)
|- stage3_rlx_membrane.wts (Membrane weights for stage 3 of loop building)
|- example_output (example output file after performed loop building)
|| - 7bvq_template_ptd_dummy_loop.pdb (loop building input pdb with a dummy ICL3, the modeling protocol required coordinates for the loop already be present)
|| - 2021-05-11_7bvq_hb1arr_icl3_kWF_MEF_production-1.silent (Compressed protein structure archive in the Rosetta Silent format)
|| - 2021-05-11_7bvq_hb1arr_icl3_kWF_MEF_production-1.fsc (File with Rosetta scores for building protein structures)
|| - 2021-05-11_7bvq_hb1arr_icl3_kWF_MEF_production-1.silent.merge.tmp (Temporary file used for protein structure archive merging)
|| - 2021-05-11_7bvq_hb1arr_icl3_kWF_MEF_production-1.log (Log file from protein structure building)

Dataset C_terminal_modeling.zip (model preparation for C terminus buidling)

|- submit_MEF_kwf_cterm.atomate_jrdd.qsub (SLURM job submission script for C terminus building)
|- all_inp (All input files used for C terminus building)
|| - disulfides.ss (File indicating disulfide bridge location)
|| - hb1arr_target.span (File indicating location of lipid membrane for the target protein)
|| - hb1arr_7bvq_icl3_built_4470002_dummy_cterm_plus_ala.span (File indicating location of lipid membrane for the template protein)
|| - hb1arr_7bvq_icl3_built_4470002_dummy_cterm_plus_ala.pdb (input pdb file with a built ICL3 and dummy C terminus, the modeling protocol required coordinates for the terminus already be present)
|| - hb1arr_target-grishn.aln (Protein sequence alignment file)
|| - hb1arr_target.fasta (Target protein sequence file in the FASTA format)
|| - ab_inito.map (map file for loop building)
|- hb1arr.200.03.3mers (Protein 3-residue fragments used for C-terminus building)
|- hb1arr.200.09.9mers (Protein 9-residue fragments used for C-terminus building)
|- kic_with_frags_mef.xml (Rosetta script in the XML format for KIC C-terminus building with fragments)
|- stage1_membrane.wts (Membrane weights for stage 1 of C-terminus building)
|- stage2_membrane.wts (Membrane weights for stage 2 of C-terminus building)
|- stage3_rlx_membrane.wts (Membrane weights for stage 3 of C-terminus building)
|- cluster_decoys.sh (Clusters structures (decoys) from a Rosetta silent file based on structural similarity, with a user-defined RMSD radius.)
|- pre-merge_rename.sh (Merge the icl3 and C_terminal)
|- example_output (example output file after performed C-terminus building )
|| - hb1arr_7bvq_icl3_built_4470002_dummy_cterm_plus_ala.pdb (input pdb file with a built ICL3 and dummy C terminus, the modeling protocol required coordinates for the terminus already be present)
|| - 2021-05-17_7bvq_kwf_mef_cterm-1.silent (Compressed protein structure archive in the Rosetta Silent format)
|| - 2021-05-17_7bvq_kwf_mef_cterm-1.fsc (File with Rosetta scores for built protein structures)
|| - 2021-05-17_7bvq_kwf_mef_cterm-1.log (Log file for built protein structures)

Dataset ligand_dock_norepinephrine.zip (RosettaLigand docking of norepinephrine to beta 1AR)

|- clean_pdb_builds (Initial files for ligand + receptor complex, receptors include C-terminal and ICL3 loops, the major helix part of the receptors are based on structures from protein data bank, users can match up the files with the source based on the second part of the file name (i.e., 3SN6 or 7BVQ) )
|| - hb1arr_7bvq_full_template_nor1_conf2.pdb (PDB file for the initial b1AR + cationic norepinephrine complex with CONF2)
|| - hb1arr_7bvq_full_template_nor1.pdb(PDB file for the initial b1AR + cationic norepinephrine complex)
|| - hb1arr_7bvq_cterm_model_180003_ala_deletion_nor1_added.pdb (PDB file for the initial b1AR + cationic norepinephrine complex with specific model of cterm)
|| - hb1arr_7bvq_cterm_model_180003_ala_deletion_nor1_conf2.pdb (PDB file for the initial b1AR + cationic norepinephrine complex with conf2)
|- ldock_rpkmin_jd.sh (RosettaLigand repacking shell script to get rid of bad contacts in the protein-ligand complex)
|- ldock-rs_jd.sh (RosettaLigand test docking shell script)
|- generate-ligand-conformers.sh (Code for generate ligand conformers and fa and cen folders)
|- ligand (RosettaLigand ligand parameter files)
||- fa (full-atom model)
||- cen (centroid model)
||- _nor1.parm (RosettaLigand ligand parameter files)
||- others are intermediate files
|- hb1arr_7bvq_full_template_nor1_conf2_t01_50k_ldock-rs.sh (RosettaLigand docking of 50K structures SLURM job submission script)
|- hb1arr_7bvq_full_template_nor1_conf2-input.pdb (input structure file for the RosettaLigand docking after repacking)
|- ligand_dock_tnew1.xml (XML file for RosettaLigand docking protocol)
|- get_top50_from_50k_pdb.run (Shell script code for getting top 50 of docked structures from the 50K output structures)

Dataset ligand_dock_S-Propranolol.zip (repeated documents were omitted, RosettaLigand docking of S-Propranolol to beta1AR)

|- clean_pdb_builds (Initial files for ligand + receptor complex, receptors include C-terminal and ICL3 loops, the major helix part of the receptors are based on structures from protein data bank, users can match up the files with the source based on the second part of the file name (i.e., 3SN6 or 7BVQ))
|- prs1_ligand (RosettaLigand S-Propranolol ligand parameter files)
|| - fa (full-atom model)
|| - cen (centroid model)
|| - _prs1.parm (RosettaLigand S-Propranolol ligand parameter files)

Dataset ligand_dock_R-Propranolol.zip (docking of R-Propranolol to beta 1 AR)

|- clean_pdb_builds (Initial files for ligand + receptor complex, receptors include C-terminal and ICL3 loops, the major helix part of the receptors are based on structures from protein data bank, users can match up the files with the source based on the second part of the file name (i.e., 3SN6 or 7BVQ))
|- ligand (RosettaLigand ligand parameter files)
|| - fa (full-atom model)
|| - cen (centroid model)
|| - _pro1.parm (RosettaLigand R-Propranolol ligand parameter files)

Dataset ligand_dock_D-sotalol.zip (RosettaLigand docking of D-sotalol to beta1AR)

|- clean_pdb_builds (Initial files for ligand + receptor complex, receptors include C-terminal and ICL3 loops, the major helix part of the receptors are based on structures from protein data bank, users can match up the files with the source based on the second part of the file name (i.e., 3SN6 or 7BVQ))
|- ligand ( ligand parameter files)
|| - fa (full-atom model)
|| - cen (centroid model)
|| - _sotp.parm (RosettaLigand d-sotalol ligand parameter files)

Dataset ligand_dock_L-sotalol.zip (RosettaLigand docking of L-sotalol to beta1AR)

|- clean_pdb_builds (Initial files for ligand + receptor complex, receptors include C-terminal and ICL3 loops, the major helix part of the receptors are based on structures from protein data bank, users can match up the files with the source based on the second part of the file name (i.e., 3SN6 or 7BVQ))
|- ligand RosettaLigand ligand parameter files)
|| - fa (full-atom model)
|| - cen (centroid model)
|| - _lstp.parm (RosettaLigand l-sotalol ligand parameter files)

Dataset D_sotalol_b1AR.zip (Molecular Dynamics simulation files for beta1AR - d-sotalol system)

|- step5_input.parm7 (Amber parameter file for the system )
|- step5_input.pdb (coordinate file for the system in the PDB format)
|- step5_input.psf (protein structure file of the system used for atom names and connectivity, can be used to visualize dcd trajectory files)
|- step5_input.rst7 (coordinate file that can be used as an input and restart file for Amber)
|- step6.0_minimization.mdin (Amber simulation input file for the minimization step)
|- step6.1-6.6_minimization.mdin (Amber simulation input files for the equilibration step 6.1 to step 6.5, respectively)
|- step7.1_production.mdin (Amber simulation input file for the production step 7.1)
|- step7_production.mdin (example Amber simulation input file for the rest of the production steps and can be used in the job submitting script)
|- step7_production_restraints_CORE_CA_NE.mdin (example Amber simulation input file using restraint for the binding pocket and the drug)
|- step7_production_restraints_all_CA_NE.mdin (example Amber simulation input file using restraint for the protein backbone and the drug)
|- step8_production_LiGaMD.mdin (example Amber simulation input file for the preparation of Gaussian accelerated MD, GaMD, and can be used in the job submitting script)
|- step8_production_LiGaMD2.mdin (example Amber simulation input file using GaMD and can be used in the job submitting script)
|- slurm_cmd.sh (job submitting script using SLURM for conventional MD, cMD, simulation)
|- slurm_GaMD.sh (job submitting script using SLURM for Gaussian accelerated MD, GaMD, simulation)
|- d_sotalol_b1_cmd.dcd (binary simulation trajectory of cMD for about 1,000 ns)
|- d_sotalol_b1_GaMd.dcd (binary simulation trajectory of GaMD for about 1,000 ns)

Dataset L_sotalol_b1AR.zip

(Molecular Dynamics simulation files for beta1AR – l-sotalol system, the listed files share the same names and guidelines as the d-sotalol simulations.)

Dataset R_propranolol_b1AR.zip

(Molecular Dynamics simulation files for beta1AR – R-propranolol system, the listed files share the same names and guidelines as the d-sotalol simulations.)

Dataset S_propranolol_b1AR.zip

(Molecular Dynamics simulation files for beta1AR – S-propranolol system, the listed files share the same names and guidelines as the d-sotalol simulations.)

Sharing/Access information

Experimental PDB files were downloaded from the Protein Data Bank
PDB 3SN6: https://www.rcsb.org/structure/3sn6
PDB 7BVQ: https://www.rcsb.org/structure/7BVQ
PDB 7BU6: https://www.rcsb.org/structure/7BU6

Code/Software

TM4-TM6-distance.tcl (VMD Tcl/Tk code for analyze the distance between TM4 and TM6)
contact-AA-ligand.tcl (VMD Tcl/Tk code for analyze the contact amino acid residues)