architvasan/PeptideDesign_OMM

Peptide design project

General steps

1. Identify literature derived binding proteins to your protein of interest using PathwayCommons

   • https://apps.pathwaycommons.org/

2. Generate multimer structure using ESMFold (can also use AlphaFold2 but saw better results with ESMFold)

   python src/fold_ai/esm_pred.py -h

3. Create solvated solvated + ionized set up using ambertools (0.15 M NaCl)

   python src/create/create_apo.py -h

4. Simulate system using OpenMM for multiple replica

   python run_openmm_mpi.py -h

5. Analyze coordinates of interest during simulation (e.g. ANCA to analyze IDRs)

   python src/analyze/heiranca_dihedrals.py -h

6. Construct MSM to identify metastable protein conformations

   python src/analyze/msm/preprocess.py -h
   python src/analyze/msm/msm.py -h
   python src/analyze/msm/metastable_trajs.py -h

7. ID residue hotspots for each conformation python src/analyze/contacts_A_B.py -h

8. For each protein of interest conformation, follow RFDiffusion protocol to generate novel binding peptides.

   • Scripts in src/peptide_design
   • Follow instructions in https://github.com/RosettaCommons/RFdiffusion.git for installation + running

9. Next:

   • Implement free energy simulations to evaluate binding energy of each generated peptide