Introduction

• Welcome! This repository contains code used for analysis of HLA-Ab crystal structures for Sampurna Mukherjee (@SampurnaM) 's MPhil by thesis, titled "Computational Analysis of HLA-Ab interactions in the context of solid organ transplantation", to be submitted to Department of Biological Sciences, University of Cambridge in 2024, as a student of EMBL-EBI, Leach Group in collaboration with Kosmoliaptsis group in University of Cambridge.
• The code in this repository was created to analyse HLA-antibody complexes in the context of solid organ transplantation.
• Please use the provided yaml file: , to create Conda environment and have dependencies installed for running code in this repo.
• The code is organised in three Jupyter notebooks :

1. The first Jupyter Notebook: Follows Objective 1 of the thesis - finding epitope residues for HLA-A*1101- 2e3 complex (PDB ID: 6ID4 using epitope features: Presence in antibody-antigen binding interface(distance), solvent accessibility and presence of non-covalent interactions (NCIs) computed as Interaction Fingerprints. This analysis is for static structures, i.e single PDB files.

   • The module sampurna_thesis was written specifically for epitope feature computation from PDB files.
   • The notebook has driver code using the functions in sampurna_thesis module and additional steps for data wrangling and final plots.
   • Objective 1 Notebook

2. The second Jupyter notebook: Follows Objective 2 of the thesis - computing the same epitope features across multiple conformations generated by molecular dynamics (MD) simulations to observe if HLA epitope residues retain epitope features across multiple structural conformations generated by MD simulations.

   Metrics used for MD simulation analysis:

   • QA check: 1D-RMSD & RMSF
     Analysis: 2D-RMSD, Fraction of native contacts, Solvent accessibility, Tanimoto Similarity Matrices and Clustered Tanimoto Similarity Matrices from Interaction Fingerprints
   • Simulation software: GROMACS 2022
   • Key packages: MDAnalysis and ProLIF
   • Objective 2 Notebook

3. Finally, the molecular dynamics simulations were performed on EMBL-EBI's CODON cluster and the system setup was performed by launching Jupyter Notebooks inside CODON-SLURM cluster. The setup notebook is also available in this repository.

Images generated from the analyses in the notebooks are present in the images folder.

Simulation files

If you are interested in having a copy of the raw simulation trajectory files, please write to arl@ebi.ac.uk . Thank you!