On the determinants of residence times and dissociation mechanisms of complexes of Interleukin-13 with its low and high affinity receptors.

File Organization Note that the numbering scheme for the mutants depicted here refers to the publications from Lupardus et al. (2010) and Moraga et al. (2015) and not to the numbering scheme from UniProt as shown in the publication. The following project folder "Publication_Data.zip" is divided into the following subfolders: "IL13Ra1" (Analysis with the low affinity receptor) "IL13Ra2" (Analysis with the high affinity receptor) Both subfolders are divided into: "tauRAMD" "MD-IFP" The "tauRAMD" folder contains the following files: tauRAMD.py (calculation of the residence time according to Kokh et al. (2018)) tauRAMD_PP_Residence_time.ipynb (calculation of the residence times according to D'Arrigo et al. (2024)) amber_prep.sh (minimization, heating and equilibration script for AMBER) amber_prep_last.sh (equilibration script for AMBER) Additionally, the "tauRAMD" contains a folder for each mutant studied. For each mutant, there is a folder called "RAMD_26kcalmol" (26kcal/mol is the force magnitude used for the RAMD simulations). The folder contains the following files: gromacs.gro (gromacs structure file) gromacs.top (gromacs topology file) index.ndx (gromacs index file) oct25_150.inpcrd (amber coordinate file before energy minimizatione and equilibration) oct25_150.pdb (binary complex pdb file with water and ions) oct25_150.prmtop (amber parameter topology file) ref-equil-NPT.crd (amber coordinate file after energy minimization and equilibration) res_times.png (statistical evaluation of the residence time calculation) res_times_summary.png (calculated residence time based on all replicas) steps_replica_1.txt (plain text file containing the number of steps needed for dissociation for all RAMD simulation referring to replica 1) steps_replica_2.txt (plain text file containing the number of steps needed for dissociation for all RAMD simulation referring to replica 2) steps_replica_3.txt (plain text file containing the number of steps needed for dissociation for all RAMD simulation referring to replica 3) steps_replica_4.txt (plain text file containing the number of steps needed for dissociation for all RAMD simulation referring to replica 4) steps_replica_5.txt (plain text file containing the number of steps needed for dissociation for all RAMD simulation referring to replica 5) steps_replica_6.txt (plain text file containing the number of steps needed for dissociation for all RAMD simulation referring to replica 6) For all mutants with representative trajecoties (IL-13Ra1: WT and DN; IL-13Ra2: WT and F107A), an additional "GROMACS" folder exists and contains another folder called REPLICA_X, where X represents the replica from which the representative trajectory was taken. The REPLICA_X folder contains the following files: confout_renum.gro (corresponds to gromacs.gro used for the corresponding RAMD simulations) gromacs_eq.tpr (input file for the equilibration in GROMACS) gromacs_eq1.mdp (parameter file for the equilibration in GROMACS) state.cpt (restart file for GROMACS used for the corresponding RAMD simulations) Furthermore, the "RAMD_26kcalmol" folder contains the subfolder "TRJ-X-Y", where X represents the replica and Y the trajectory number. The folder contains the following files: Ra1(2)_MUTANT.mp4 (movie of a representative dissociation event) gpu-out.****** (output file of the RAMD simulation) gromacs_ramd.tpr (input file for the RAMD simulation in GROMACS) state.cpt (restart file for GROMACS used for the corresponding RAMD simulations) tr.xtc (trajectory file used for generating the representative movies) Besides the "tauRAMD" folder, there is the "MD-IFP" folder. It contains the following folders: "analysis_scripts" "input_scripts" "pkl_files" The "analysis_scripts" folder contains the following files: IFP_analysis_RAMD_PP_MUTANT_moraga_5c.py (plotting script that analysis the output of the MD-IFP analysis; there is one script per mutant) JN_scripts.py (important functions that are imported by the plotting script) MD-IFP-3.8-scipy.yml (conda evironment as a yaml file to run IFP_analysis_RAMD_PP_MUTANT_moraga_5c.py The "input_files" folder contains the following files: IFP-Analysis-EQ.py (MD-IFP script for the analysis of equilibration trajectories) IFP-Analysis.py (MD-IFP script for the analysis of RAMD trajectories) IFP-Analysis_20.py (MD-IFP script for the analysis of RAMD trajectories for mutants with 20 trajectories per replica instead of 15) combine_all_data.py (script that compresses the output of the MD-IFP analysis into pkl files) combine_all_data_20.py (script that compresses the output of the MD-IFP analysis into pkl files for mutants with 20 trajectories per replica) Unfortunately, the conda environment necessary for performing the analysis has been lost but can be adapted from https://github.com/HITS-MCM/MD-IFP/blob/master/MD-IFP.yml The "pkl_files" folder contains the following files: MUTANT-EQ.pkl (pkl file that contains the output of the MD-IFP analysis for the equilibration trajectories) MUTANT-RAMD.pkl (pkl file that contains the output of the MD-IFP analysis for the RAMD trajectories)