Study and evaluation of the unbinding kinetics of Mineralocorticoid (MR and MR-S810L) receptor steroid agonist Cortisol (COL), Aldosterone (AS4), and Progesterone (STR) ligands using Molecular Dynamics (MD) and Monte Carlo (MC) simulations, LiGaMD and LiBELa softwares respectively.
- Prepare the input files: PDB and mol files of the Mineralocorticoid (MR) and MR mutation (S810L) ligands and the Aldosterone (AS4), Cortisol (COL), and Progestero (STR) proteins
- Create the Molecular Dynamics (MD) simulations for the MR/MR_mut - aldosterone/cortisol/progesteron system
- Create the Monte Carlo (MC) simulations for the MR aldosterone/cortisol/prgesteron systems
- Contrast MD and MC simulations, does the MC simulation show the same behavior as MC?
- PDB-rcsb
- GaMD
- GamD-OpenMM
- OpenMM
- LiBELa
- Amber Manuals
- Chimera User Guide - commands
- Living Journal of Computational Molecular Science
- Thesis_Alessandro_Silva_Nascimento.pdf, pag 127
- Highly accurate protein structure prediction with AlphaFold
- Aldosterone and mineralocorticoid receptors: Orphan questions
- Ligand Dissociation from Estrogen Receptor Is Mediated by Receptor Dimerization: Evidence from Molecular Dynamics Simulations
Reports made during the internship. Here you can find weekly updates and the final report with some conclusions.
Mineralocorticoid (MR) protein interaction with aldosteron (AS4) ligand
Mineralocorticoid (MR) protein interaction with cortisol (COL) ligand
This image is obtained using the PlotEnergies.ipynb notebook that use jscatter pacakge to import dat files and matplotlib to plot.
These image are obtained using the notebooks Plots_MC.ipynb, which use jscatter pacakge to import dat files and matplotlib to plot, and PyEMMA_AS4.ipynb, which uses PyEMMA to analyze the simulatiosn outputs.
- LiGaMD is not eble to reproduce ligand un/binding events, while or nether LiGaMD2
- LiBELa software is abel to emulate the ligand un/binding events when a high temperature is used, above of 5000K
- Analyzing MC simulations with PyEMMA shows that in the tal sysmtem the ligand scape easier than in the other systems, talk also about mutations.
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