Data for the grant "Elucidation of molecular mechanisms of sex-based arrhythmias"

This dataset is associated with the In the American Heart Association (AHA) sponsored career development award 19CDA34770101 "Elucidation of molecular mechanisms of sex-based arrhythmias, in which we focused on hormone and/or drug interactions with the human Kv11.1 potassium channel (encoded by the hERG - human Ether--go-go-Related Gene), a major contributor to cardiac action potential repolarization and an anti-target for diverse drug molecules. The dataset contains MD simulations of hERG channel - hormone and/or drug interactions as well as their analyses. Multi-microsecond-long umbrella sampling MD simulations as well as fragment-based Site-Identification by Ligand Competitive Saturation (SILCS) docking results were performed and presented here.

Description of the data and file structure

The dataset includes gzipped tar ball files, which contain multiple files, which need to be extracted and uncompressed.

herg_o2_e2b_zm50_namd_u01_r1_50.tar.gz.partaa - gzipped tar ball file (part 1/2) for the hERG channel - estradiol (E2b) interactions using all-atom umbrella sampling molecular dynamics (US-MD) simulations

herg_o2_e2b_zm50_namd_u01_r1_50.tar.gz.partab - gzipped tar ball file (part 2/2) for the hERG channel - estradiol (E2b) interactions using all-atom umbrella sampling molecular
dynamics (US-MD) simulations

herg_o2_dht_zm50_namd_u01_r1_70_partial.tar.gz - gzipped tar ball file for the hERG channel - dihydrotestosterone (DHT) interactions using all-atom umbrella sampling molecular dynamics (US-MD) simulations.

herg_o2_dht_zm50_namd06_pullx_us0x.tar.gz - gzipped tar ball file for the hERG channel - dihydrotestosterone (DHT) interactions using initial 50 ns-long equilibration and five 90-ns-long pulling (steered MD) runs.

herg_o2_e2b_zm50_namd06_pullx_us0x.tar.gz - gzipped tar ball file for the hERG channel - estradiol (E2b) interactions using initial 50 ns-long equilibration and five 90-ns-long pulling (steered MD) runs.

hormone_herg_silcs_docking_.tar.gz - gzipped tar ball file for the hERG channel - hormone and/or drug interactions using SILCS MC fragment-based molecular docking.

Extraction and decompression instructions for .tar.gz:
tar xvfz FILE_NAME.tar.gz
Or
gunzip FILE_NAME.tar.gz
tar xvf ILE_NAME.tar

Split tar.gz files (.partaa and .partb) need to be combined first
cat FILE_NAME.tar.gz.partaa FILE_NAME.tar.gz.partab > FILE_NAME.tar.gz

After extraction of all those files the following folders will be created:

herg_o2_e2b_zm50_namd_u01_r1_50/

herg_o2_dht_zm50_namd_u01_r1_70_partial/

herg_o2_dht_zm50_namd06_pullx_us0x/

herg_o2_e2b_zm50_namd06_pullx_us0x/

hormone_herg_docking/

Below is the description of each of these folders as well as subfolders and files within them. There are also README files within some of those folders with more detailed information.

Folder herg_o2_e2b_zm50_namd_u01_r1_50/ - data for all-atom umbrella sampling molecular dynamics (US-MD) simulations of hERG channel - estradiol (E2b) interactions.
90 US-MD windows were used with 50 ns per window, 4,500 ns of MD simulation time in total. Initial and final coordinates in the PDB and NAMD binary (.coor) formats, binary velocity (.vel) and system size (.xtc) files, protein structure files (.psf), NAMD input (.inp) and output (.out or .log) files., trajectory files for collective variables (.traj), force field parameter files (.par) are included for each US-MD run. Binary trajectory (.dcd) files are not included.

Subfolders 1/ to 90/ contain data for each of US-MD runs 1 to 90 corresponding to Z value of -50 to -5.5 Angstrom. Z distance is counted with respect to center of mass (COM) of C-alpha atoms of selectivity filter (SF) residues 624-628. In each folder there are runs 1-50, each of them corresponds to 1 ns of the simulation.
File names are:step9.[run_number]_production.[extension]
For instance, for window 5 and run 10 files are:
5/step9.10_production.col - NAMD collective variable (colvar) file, text format, used by NAMD software and can be read by NAMD or text editor
5/step9.10_production.colvars.state - NAMD collective variable (colvar) state file, text format, output of NAMD software, contains latest values of colvars at the end of each run
5/step9.10_production.colvars.traj - NAMD collective variable (colvar) trajectory file, text format, output of NAMD software, contains trajectory of colvars for the whole run
5/step9.10_production.coor - NAMD binary coordinate file at the end of each run, can be read by VMD or NAMD software after reading PDB or PSF file containing atom names and topology
5/step9.10_production.inp - NAMD input file, text format, can be read using text editor and by NAMD software
5/step9.10_production.log - NAMD output file, text format, can be read using text editor
5/step9.10_production.vel - NAMD binary velocity file at the end of each file, can be read by VMD or NAMD software after reading PDB or PSF file containing atom names and topology.
5/step9.10_production.xsc - NAMD unit cell file (x, y, z and angles) at the end of each run, text file, can be read using text editor, NAMD and VMD software
5/step9.10_production.xst NAMD unit cell file (x, y, z and angles) trajectory for the entire run, text file, can be read using text editor, NAMD and VMD software
For each window we also have initial coordinates and velocity files
5/step8.5_production.coor - initial NAMD binary coordinate file for each US-MD window, can be read by VMD or NAMD software after reading PDB or PSF file containing atom names and topology
5/step8.5_production.vel - initial NAMD binary velocity file for each US-MD window, can be read by VMD or NAMD software after reading PDB or PSF file containing atom names and topology
5/step8.5_production.xsc - initial NAMD unit cell file (x, y, z and angles) at the end of each run, text file, can be read using text editor, NAMD and VMD software.
5/step5_assembly.namd.str - NAMD stream file, text format, can be read by NAMD software and text editor
5/checkfft.str - NAMD stream file for fast Fourier transform (FFT) parameters, text format, can be read by NAMD software and text editor
5/production_restraint.namd.col - NAMD collective variable (colvar) initial file, text format, used by NAMD software and can be read by NAMD or text editor

Subfolder all_inp/ contain input files and job submission scripts, common for all US-MD windows or templates (.templ) used to generate ones specific for each US-MD run. All files are in text format and can be read by any text editor.
all_inp/checkfft.str - NAMD stream file for fast Fourier transform (FFT) parameters, text format, can be read by NAMD software and text editor
all_inp/herg_mx0_cometgpu_us_wx_02.qsub.templ - SLURM job submission script template for SDSC Comet GPU nodes
all_inp/herg_mx0_comet_us_wx_02.qsub.templ - SLURM job submission script template for SDSC Comet CPU nodes
all_inp/production_restraint.namd.col.templ - NAMD stream file template, text format, can be read by NAMD software and text editor
all_inp/step5_assembly.namd.str - NAMD collective variable template file, text format
all_inp/step9.1_production.inp.templ - NAMD input file template for run #1
all_inp/step9_production.inp - NAMD input file template for runs #2-50

Subolder toppar/ contains CHARMM parameter files in text format, all files can be read by any text editor, NAMD or CHARMM software. par_.prm - parameter files for different biomolecular systems (proteins, lipids etc.). toppar_.str - auxiliary parameter files for specific molecules (e.g., water).

Subfolder restraints/ contains NAMD files for restraints used in the MD simulations. All files are in text format and can be read by any text editor, NAMD or CHARMM software. *.ref files are reference coordinates (in the PDB text format) with restraints written as a previous to the last column (e.g., 1.00 - restraint, 0.00 - no restraint) for each atom. write_ca_rest.tcl is VMD script in the text format, which generates those restraint files. dihe.txt is restraint file for dihedral angles.

Subfolder e2b/ contains CHARMM topology (e2b.rtf) and parameter (e2b.prm) files for estradiol in the text format, can be read by NAMD or CHARMM software.

Subfolder pmf_convergence/ contains text files of US_MD collective variables to compute free energy or potential of mean force (PMF) profile using weighted histogram analysis method (WHAM).
pmf_[win_num]_[run_num].dat are text data files for US_MD window and run number.
wham_old2_newf.f90 - WHAM program script written in Fortran 90, can be compiled using GNU Fortran.
wham_old2_newf.exe - WHAM program executable in the binary format, can be run on x86 computers using Linux
wham.inp - text input file for WHAM program
wham_clean.run - shell script in text format to remove unneeded files.
win_ene_hist2o.run - shell script in text format to generate PMF histogram.

Files in the parent subfolder ./
check_max_run.run - shell script in text format to check max run for each US-MD window
convert_NAMD2WHAM*.sh - shell script in text format to convert colvar trajectories from NAMD to WHAM program format
copy_run_qsub_us_windows.run - - shell script in text format to copy US-MD window files
e2b*.qsub - queue submission scripts for different platforms and for different US-MD windows (w#).
edit_pmf.sh - shell script in text format to edit information in WHAM colvar trajectory files if needed.
make_all_us_windows.run - shell script in text format to generate all US-MD windows
random_num.txt - text file with random numbers.
README.txt - text file with description of MD simulation procedure.
shuffle_windows_new.py - Python script in text format to generate non-repeating random numbers for subsequent US-MD windows.
shuffle_windows.py - Python script in text format to generate random numbers for subsequent US-MD windows (not used).
step5_assembly.namd.pdb - Initial molecular coordinates in the PDB text NAMD compatible format.
step5_assembly.pdb - Initial molecular coordinates in the PDB text original format.
step5_assembly.psf - CHARMM protein structure file (PSF) in the text format.
step5_assembly.xplor_ext.psf - CHARMM protein structure file (PSF) in the extended text format.

Folder herg_o2_dht_zm50_namd_u01_r1_70_partial/ - data for all-atom umbrella sampling molecular dynamics (US-MD) simulations of the hERG channel - dihydrotestosterone (DHT) interactions.
90 US-MD windows were used with up to 70 ns per window, 6,300 ns of MD simulation time in total. Initial and final coordinates in the PDB and NAMD binary (.coor) formats, binary velocity (.vel) and system size (.xtc) files, protein structure files (.psf), NAMD input (.inp) and output (.out or .log) files, trajectory files for collective variables (.traj), force field parameter files (.par) are included for each US-MD run. Binary trajectory (.dcd) files are not included. Some files not important for free energy and diffusion coefficient calculation analysis are missing but can be re-generated using new runs if needed.

Subfolders 1/ to 90/ contain data for each of US-MD runs 1 to 90 corresponding to Z value of -50 to -5.5 Angstrom. Z distance is counted with respect to center of mass (COM) of C-alpha atoms of selectivity filter (SF) residues 624-628. In each folder there are runs 1-30 (windows 1-50) or 1-15 (windows 51-90), each of them corresponds to 1 ns of the simulation.

Subfolder all_inp/ contain input files and job submission scripts, common for all US-MD windows or templates (.templ) used to generate ones specific for each US-MD run. All files are in text format and can be read by any text editor.

Subolder toppar/ contains CHARMM parameter files in text format, all files can be read by any text editor, NAMD or CHARMM software. par_.prm - parameter files for different biomolecular systems (proteins, lipids etc.). toppar_.str - auxiliary parameter files for specific molecules (e.g., water).

Subfolder restraints/ contains NAMD files for restraints used in the MD simulations. All files are in text format and can be read by any text editor, NAMD or CHARMM software.

Subfolder dht/ contains CHARMM topology (dht.rtf) and parameter (dht.prm) files for dihydrotestosterone in the text format, can be read by NAMD or CHARMM software.

Subfolder pmf_convergence/ contains text files of US_MD collective variables to compute free energy or potential of mean force (PMF) profile using weighted histogram analysis method (WHAM).

Files in the parent subfolder ./
check_max_run.run - shell script in text format to check max run for each US-MD window
convert_NAMD2WHAM*.sh - shell script in text format to convert colvar trajectories from NAMD to WHAM program format
copy_run_qsub_us_windows.run - - shell script in text format to copy US-MD window files
dht*.qsub - queue submission scripts for different platforms and for different US-MD windows (w#).
edit_pmf.sh - shell script in text format to edit information in WHAM colvar trajectory files if needed.
make_all_us_windows.run - shell script in text format to generate all US-MD windows
random_num.txt - text file with random numbers.
README.txt - text file with description of MD simulation procedure.
shuffle_windows_new.py - Python script in text format to generate non-repeating random numbers for subsequent US-MD windows.
shuffle_windows.py - Python script in text format to generate random numbers for subsequent US-MD windows (not used).
step5_assembly.namd.pdb - Initial molecular coordinates in the PDB text NAMD compatible format.
step5_assembly.pdb - Initial molecular coordinates in the PDB text original format.
step5_assembly.psf - CHARMM protein structure file (PSF) in the text format.
step5_assembly.xplor_ext.psf - CHARMM protein structure file (PSF) in the extended text format.
all_ligand_tumble_hERG.tcl - example CMD TCL script for ligand tumbling analysis (it was used for a different ligand and needs to be modified for DHT if needed).

Please see detailed file type description for the folder herg_o2_e2b_zm50_namd_u01_r1_50/ above.

Folder herg_o2_dht_zm50_namd06_pullx_us0x/ - data for initial 50 ns-long equilibration and five 90-ns-long pulling (steered MD) runs of the hERG channel - dihydrotestosterone (DHT) interactions.\
Initial and final coordinates in the PDB and NAMD binary (.coor) formats, binary velocity (.vel) and system size (.xtc) files, protein structure files (.psf), NAMD input (.inp) and output (.out or .log) files., trajectory files for collective variables (.traj), force field parameter files (.par) are included for each US-MD run. Binary trajectory (.dcd) files are not included.

Subfolder CHARMM-GUI/ has files in text format generated by input generator, bilayer builder by www.charmm-gui.org

Subfolder initial/ contains CHARMM scripts (all in text format) to generate initial hERG channel - hormone structure

Subfolder namd06/ contains NAMD files for 50 ns-long equilibration

Subfolders namd_pullf1[1-5]/ contain NAMD files for five 90-ns-long pulling (steered MD) runs.

Subfolder namd_us02/ contains NAMD files for US-MD simulation (initial files and templates only).

Please see detailed description of file types for the description of the folder herg_o2_e2b_zm50_namd_u01_r1_50/ above and detailed instructions on setting up and running simulations in the file README.txt

Folder herg_o2_e2b_zm50_namd06_pullx_us0x/ - data for initial 50 ns-long equilibration and five 90-ns-long pulling (steered MD) runs of the hERG channel - estradiol (E2b) interactions.
Initial and final coordinates in the PDB and NAMD binary (.coor) formats, binary velocity (.vel) and system size (.xtc) files, protein structure files (.psf), NAMD input (.inp) and output (.out or .log) files., trajectory files for collective variables (.traj), force field parameter files (.par) are included for each US-MD run. Binary trajectory (.dcd) files are not included.

Subfolder CHARMM-GUI/ has files in text format generated by input generator, bilayer builder by www.charmm-gui.org

Subfolder initial/ contains CHARMM scripts (all in text format) to generate initial hERG channel - hormone structure

Subfolder namd06/ contains NAMD files for 50 ns-long equilibration

Subfolders namd_pullf1[1-5]/ contain NAMD files for five 90-ns-long pulling (steered MD) runs.

Subfolder namd_us02/ contains NAMD files for US-MD simulation (initial files and templates only).

Please see detailed description of file types for the description of the folder herg_o2_e2b_zm50_namd_u01_r1_50/ above and detailed instructions on setting up and running simulations in the file README.txt

Folder hormone_herg_docking/ - data for SILCS-MC fragment-based molecular docking the hERG channel - hormone and/or drug interactions.
Only final PDB files containing hERG channel and drug and/or hormone molecules for top-scoring (lowest interaction energy) binding poses are included. All files are in the text PDB format and can be read by any text editor, multiple molecular visualization software (VMD, USCF Chimera or ChimeraX, PyMol etc.)

Sharing/Access information

Links to other publicly accessible locations of the data: None

Data was derived from the following sources: None

Code/Software

All-atom molecular dynamics (MD) simulations were performed using nanoscale molecular dynamics (NAMD) software, version 2.13 or 2.14 and were analyzed using visual molecular dynamics (VMD) software version 1.9.3.

Fragment-based Site-Identification by Ligand Competitive Saturation (SILCS) molecular docking calculations used software 2022.2. SILCS fragment-generation MD simulation runs used Grimaces software version 2020.2 or later.