Somatic hypermutation-mediated paratope flexibility improves the cross-reactivity of human malaria antibodies -- Molecular Dynamics dataset

4493 Manuscript Data
====================

author: Anton Hanke
size of uncompressed folder: ~19Gb.
DOI: 10.5281/zenodo.11470585

# Standard MD simulation data

Standard Simulations were generated with gromacs 2021.5 using the charmm36m forcefield Juli 2021 release tarball (https://mackerell.umaryland.edu/download.php?filename=CHARMM_ff_params_files/charmm36-jul2021.ff.tgz).
Post processed (PBC) simulations are structured as follows:
Mature generally refers to the wildtype 4493 antibody.

- simulations/standardMD
  |
  |- prod.mdp                                      example production mdp file used to run all production simulations.
  |
  |- mature                                        Mature simulation set. (folder and file naming the same in all simulation directories)
  |  |- {peptide}_{replicate}_prod.gro             {peptide} = peptide; {replicate} = standard MD replicate
  |  |- {peptide}_{replicate}_prod.tpr
  |  `- {peptide}_{replicate}_prod_align_noPBC.xtc (10Frames/ns)
  |
  |- mature_rerun                                  Additional set of replicates with the wildtype 4493.
  |- matureCapped                                  Set of simulations with termini capped peptides
  |- mature_nanpv2                                 Set of simulations with NPDP similar positioning of NANP
  |- wo_pep                                        Set of simulations without peptides for germline and mature
  `- germline                                      Set of germline simulations.

# RAMD simulation data

RAMD simulations were generated with gromacs_2020.5 patched with RAMDv2 modified to account for the connected multiple ligand groups.
(Source code provided as tar file ./sw/gromacs_ramd_patchv2.tar.gz)

Not all trajectories contain an unbinding event (gromacs CUDA bug.). 
These trajectories were not considered in the analysis of simulations. 

- simulations/ramd
  |
  |- prod.mdp                                                         Exemplary production mdp file with RAMD settings, these were used in all trajectories w/
  |                                                                   differing RAMD random seed.
  |
  |- mature_2.625kcalmolA_4.0_3.0
  |  |- {peptide}_{replicate}_prod_{startFrame}.gro                   {peptide} = peptide; {replicate} = standard MD replicate; {startFrame} = Frame in standard MD used to start simulation.
  |  |- {peptide}_{replicate}_prod_{startFrame}.tpr
  |  |- {peptide}_{replicate}_prod_{startFrame}.ndx
  |  |- {peptide}_{replicate}_prod_{startFrame}_align_noPBC.xtc       (100Frames/ns) Files omited due to size -- available on request.
  |  `- {peptide}_{replicate}_prod_{startFrame}_lastframe.pdb         Last frame of the processed RAMD trajectory.
  `- gl_2.625kcalmolA_4.0_3.0

# Analysis

- analysis
  |
  |- entropie                                                         Quasi harmonic entropy estimation.
  |  |- inp                                                           Concatenated & Bootstrapped, coarse-grained and aligned trajectories of all systems
  |  |- out                                                           CPPTRAJ runs to calculate QHE on the bootstrapped trajectories
  |  |- run_complex.sh                                                Script running analysis.
  |  |- ana.py                                                        Script to calculte average and std of QHE for each system. (generates *.out *.tsv *.png)
  |  |- cg.py                                                         Script used to bootstrap, coarse-grain align and build average structure with.
  |  `- delta_entropies.ods                                           Excel file used to calculate Tab 1. in Main text of paper from entropies.out.
  |
  |- mmpbsa                                                           MMPBSA calculations (MM + SolvEnergy) with gmx_MMPBSA
  |  |- inp                                                           Input trajectories and topologies processed for MMPBSA
  |  |- out/gmx_mmpbsa                                                Output directories in which gmx_MMPBSA was run.
  |  |  ` *.dat                                                       Output files containing calculated energy terms from gmx_MMPBSA.
  |  |- mmpbsa.in                                                     MMPBSA input file used to run analysis.
  |  |- plot_results.py                                               Python script to plot correlation of MMPBSA output with experimental data
  |  |- pca_eig_extr.py                                               Script to reduce simulations to regions of high probability density within trajectory (not used in the present analysis)
  |  |- slurm-91315023.out                                            Log file of the analysis run
  |  `- run_mmpbsa.sh                                                 Shell script to run the MMPBSA analysis (generates input and output file trees).
  |
  `- ramd                                                             RAMD analysation.
     |- run.sh                                                        Shell script to run the analysis
     |- run_ramd_ana.py                                               Python script called by `run.sh` to run the analysis using `ramdAnalysis.py`
     |- contact_clusters.py                                           Python script to generate plots based on output of the analysis.
     |- ramdAnalysis.py                                               Python module containing analysis classes called/used within `run_ramd_ana.py`
     |                                                                Based on tauRAMD & Fingerprint analysis by Dr. Daria Khokh (https://doi.org/10.1021%2Facs.jctc.8b00230; https://doi.org/10.1063%2F5.0019088)
     |- abrun.*                                                       Log files from the present run
     |- *.svg; *.png                                                  Analysis output files.
     |- tramd_patchv2/                                                Output PDB structures from the analysis (excluded due to size, available on request)
     `- representatives.pse                                           Pymol session of cluster representatives along unbinding for germline and wildtype with contact probabilities within the
                                                                      cluster mapped as b-factor.

# Figures

- figure_pdbs                                                         PDB files (and pymol sessions) used to generate figures in the papers main text.