Data · dataset · 2024
Data from: Elucidation of molecular mechanisms of sex-based arrhythmias
Listed in DataCite
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.
Description
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 repolarization and an anti-target for diverse drug molecules. We performed a comprehensive set of in silico atomistic modeling and simulations on hERG structure and function modulation by sex hormones in combination with hERG channel blockers with different proclivities for arrhythmogenesis.
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These studies were informed by and will also guide electrophysiological experiments on cardiomyocytes and hERG-expressing HEK cells by our collaborators. Molecular dynamics (MD) simulation and molecular docking data, presented here and validated by electrophysiological recordings, will provide us with quantitative estimates of such hormone modulatory effects and will be used for elucidation of molecular mechanisms of sex-dependent heart rhythm abnormalities and thus the ways to combat them via rational design of sex-specific cardiac safe pharmaceuticals and/or their dose adjustments.
The dataset contains MD simulations of hERG channel - hormone and 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.
Links
Where it is published
- Repository landing page datadryad.org/dataset/doi:10.25338/B8F342 ↗
landing page · from DataCite
- DOI doi.org/10.25338/b8f342 ↗
DOI / persistent id · from DataCite
Documentation and papers
- Creative Commons Zero v1.0 Universal creativecommons.org/publicdomain/zero/1.0/legalcode ↗
license · from DataCite
- IsCitedBy 10.1161/circ.140.suppl_1.10254 doi.org/10.1161/circ.140.suppl_1.10254 ↗
publication · from DataCite
- IsCitedBy 10.1101/635441 doi.org/10.1101/635441 ↗
publication · from DataCite
- IsCitedBy 10.1161/circresaha.119.316404 doi.org/10.1161/circresaha.119.316404 ↗
publication · from DataCite
- IsCitedBy 10.1016/j.yjmcc.2021.05.015 doi.org/10.1016/j.yjmcc.2021.05.015 ↗
publication · from DataCite
- IsCitedBy 10.1161/circ.146.suppl_1.15504 doi.org/10.1161/circ.146.suppl_1.15504 ↗
publication · from DataCite
Catalogue records · 2
- DataCite API api.datacite.org/dois/10.25338/b8f342 ↗
metadata API · from DataCite
- DataCite Commons commons.datacite.org/doi.org/10.25338/b8f342 ↗
catalogue entry · from DataCite
Topics
- Stated by source
- Basic medicine
- Inferred from text
- Heart 75% · Simulation 75%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| DataCite | 10.25338/b8f342 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · DataCite | connector:datacite@1.0.0 | /data/attributes/rightsList |
| byte_size | source · DataCite | connector:datacite@1.0.0 | |
| concepts[anatomy].local:anatomy:heart | enrichment · DataCite | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].fos:basic-medicine | source · DataCite | connector:datacite@1.0.0 | |
| concepts[method].local:method:simulation | enrichment · DataCite | keyword-concept-rules@1.0.0 | title+description (75%) |
| created_date | source · DataCite | connector:datacite@1.0.0 | |
| description | source · DataCite | connector:datacite@1.0.0 | /data/attributes/descriptions |
| license | source · DataCite | connector:datacite@1.0.0 | /data/attributes/rightsList |
| publication_date | source · DataCite | connector:datacite@1.0.0 | /data/attributes/dates |
| title | source · DataCite | connector:datacite@1.0.0 | /data/attributes/titles/0/title |
| version_label | source · DataCite | connector:datacite@1.0.0 |