Elucidation of molecular mechanisms of sex-based arrhythmias

Female sex has been shown to be an independent risk factor for both inherited and acquired heart rhythm abnormalities, such as long QT syndrome (LQTS) and associated arrhythmias. Notably, female sex is a key element in up to 70% prevalence of drug-induced acquired LQTS, However, fundamental molecular mechanisms that explain this phenomenon are not well understood. Previous experimental and clinical studies suggested that it is likely related to differential levels of sex hormones (estradiol, progesterone and testosterone) playing opposite roles in pro-arrhythmia proclivities, exacerbating or mitigating effects of mutations or drugs on cardiac ion channels.  In the American Heart Association (AHA) sponsored career development award 19CDA34770101 \"Elucidation of molecular mechanisms of sex-based arrhythmias\" we focused on hormone interactions with the human Kv11.1 potassium channel (encoded by the hERG - human Ether-à-go-go-Related Gene), a major contributor to cardiac action potential re..., The dataset was collected using molecular dynamcis (MD) simulations and fragment-based Site-Identification by Ligand Competitive Saturation (SILCS) molecular docking calculations of the wild-type hERG potassium channel model based on the cryogenic electron microscopy (cryo-EM structure) with PDB ID: 5VA2. Pore and voltage sensing domain residues 405-668 were used in the model. Rosetta structural modeling was used for de novo missing loop building.
hERG channel models in a ~260 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer soaked by 0.15 M aqueous KCl solution and a  hormone molecule initially placed  in aqueous solution under .  All simulations were run using NAMD 2.13 or later in the NPT ensemble at 310 K and 1 atm pressure using Nose-Hoover thermostat and Langevin piston barostat. Standard cutoff scheme and particle mesh Ewald (PME) will be used for non-bonded interactions. Standard CHARMM biomolecular force fields (C36 for lipids, CHARMM36m for protein and sta..., PDB files contaning molecular structures can be opened with multiple molecular modeling and visualization software such as VMD,  UCSF Chimera or ChimeraX, PyMol etc. 
Protein structure files (PSF) containing system topologies and molecular dynamics (MD) simulation trajectory files in the binary DCD format can be opened using VMD or PyMol software. 
Input and output files can be opened using any text editor.
 
 , # Title of Dataset

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...