This is a repository storing data from molecular dynamics simulations of transmembrane proteins involved in remyelination pathways (OPC differentiation), as well as Galaxy workflows and python scripts for automated analysis and plotting of simulation data.
Loss of myelin, the protective covering surrounding the axons of neurons, is the driver of many neurodegenerative disorders including multiple sclerosis (MS). Most current therapeutic approaches today involve immunomodulating agents, which target the inflammatory response of the disease. Recent efforts have given way to a new approach: targeting pathways that induce remyelination of these axons. This can be done by promoting the differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes, which directly repair the myelin sheaths and help reverse the effects of the disease. Target identification in these pathways remains challenging, but there is evidence that inhibition of certain transmembrane proteins within the G-protein coupled receptor (GPCR) family, is a key step in promoting OPC differentiation. The work associated with this repository models binding of the M1 muscarinic receptor and H3 histamine receptors by two compounds with known in vitro activity.
The contents of this repository are as follows:
- Analysis_Plotting_Scripts: This holds a copy of the python scripts used to generate the final plots in the analysis.
- Data: This folder contains all data associated with each simulated system. This includes the initial protein and ligand input files obtained from molecular docking, the archives from building the full protein-membrane system with these files using CHARMM-GUI, and output files from all analysis conducted with and without Galaxy tools. The outputs for center-of-mass distance (COMd) and binding free energy analysis were generated by using gromacs2022 and gmx_mmpbsa on the commandline, respectively.
- Galaxy_Workflows: This folder contains the primary Galaxy workflows involved in this work, including molecular docking with AutoDock Vina, post-processing of gromacs trajectories, as well as a full analysis of the trajectories.