Allosteric signal transduction in FXR/RXR heterodimers bound to steroidal antagonists.
Bile acids are steroidal signalling molecules that regulate glucose, lipid and energy homeostasis through the farnesoid X receptor (FXR) and the G-protein bile acid receptor 1 (GPBAR1). FXR is a nuclear receptor and a transcription factor: an N-terminal DNA-binding domain is connected to a ligand-binding domain (LBD) made of a three-layered α-helical sandwich (helices H1–H12). The LBD holds a large lipophilic ligand-binding pocket and the activation function-2 (AF2) surface (helices 3, 4, 5 and 12), which recruits coactivators or corepressors depending on the bound ligand.
This repository analyzes how steroidal antagonists change the conformational dynamics and allosteric communication of the FXR/RXR heterodimer.
| File | Description |
|---|---|
MSM_FXR-RXR-gmf.ipynb |
Markov state model (PyEMMA): featurization, clustering, implied timescales, metastable states |
Angle-Vector-domain.ipynb |
Angle between domain vectors along the trajectory (MDAnalysis) |
n5states_state01–05.pdb |
Representative structures of the five metastable states |
Python 3 with Jupyter and the libraries listed below. Trajectories and Schrödinger Suite outputs are not included in this repository.
pip install jupyter numpy matplotlib MDAnalysis pyemma mdtraj nglview mdshareGlaucio Monteiro Ferreira — Research Associate, Institute of Chemistry, University of São Paulo (IQ-USP) · LIBNM · Ferreira Lab · ORCID · FAPESP profile · gmf@usp.br