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 trajectorie (XTC/DCD) 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 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 (combined_secstr_8sim.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.