Mechanistic insights into CFTR function from molecular dynamics analysis of electrostatic interactions

MD simulations of human CFTR (PDB 6O2P)Equilibrium MD simulations were performed on the ATP-bound CFTR structure, with and without the potentiator VX-770 (Ivacaftor). The protein is embedded in a heterogeneous lipid bilayer composed of POPC, POPE, POPS, cholesterol (CHL1), and the sphingolipid DSM, at an approximate 3:3:2:1:1 ratio. Simulations were run using the CHARMM36 force field and the GROMACS MD engine. Each folder contains the input files and trajectories required for analysis. Each simulation contains the input pdb file and the trajectory (XTC) required for analysis (e.g, apo1.pdb and apo1.xtc). GROMACS binary input files (.tpr) for all simulations, enabling re-running of the MD trajectories are provided. In addition to the trajectories, the repository includes the topology and parameter files:--> System topology files (.top) for both the apo system and the VX-770–bound system.--> Force-field parameter files (.itp) provided in compressed archives (toppar_…zip), including:• CHARMM36 force-field parameters• lipid topologies for POPC, POPE, POPS, CHL1 and DSM• VX-770 topology/parameter files generated through CHARMM-GUI CGenFF VLDM analysisThe archive VLDM.zip contains the material used to perform the Laguerre diagram-based contact analyses with VLDM v12. It includes the VLDM executable, the required parameter files for atoms and residues/molecules, and the auxiliary scripts needed to run VLDM on PDB frames extracted from the MD trajectories. The archive also contains the scripts used to extract, aggregate and analyze the VLDM outputs for the different classes of interactions reported in the manuscript, including residue–residue electrostatic contacts, residue–ion contacts and residue–lipid polar contacts. A README file is provided with instructions describing the organization of the archive and the workflow required to reproduce the VLDM-based analyses (including the tsv files mentioned below) and associated supplementary figures. More details on the VLDM program can be found on GitHub: https://github.com/elbahnsi/VLDM Processed analysis files (TSV/CSV files)These include residue side chain – side chain contacts (PS.tsv, QNPS.tsv), side chain – main chain contacts (PSmain.tsv, QNPSmain), residue–lipid contacts (Lipids.tsv, QN_Lipids.tsv) and residues-anion contacts (Anion.tsv, QN_Anion.tsv), and secondary-structure analysis (secstr.csv, showing percentage of alpha helix along each MD). Python notebook used for generating figures of the manuscriptThe notebook analysis_fig_pub.ipynb contains the exact code used to generate the supplementary figures using the processed analysis files.