mm_2024

Workshop: Introduction to Rosetta

Description

• We will outline basic methods of working with protein design using pyRosetta, ProteinMPNN and RFDiffusion.
• Duration: 90 minutes
• Objectives: be able to
  • Understand how to setup modeling with Rosetta
  • Understand how to setup protein folding simulations in Rosetta
  • Understand how to vary a binding sequence using ProteinMPNN
  • Understand how to generate new protein scaffolds using RFDiffusion

Jupyter notebooks

• PyRosetta Workshops.
• The github repo (PyRosetta) is here
• ProteinMPNN basic and example
• RFDiffusion

Required software and resources

• Easiest way is to use Google Colab Google Drive - see tutorial for initialization instructions. However, this will require a lengthy download.
• Or you need local access to a Jupyter notebook evironment with pyRosetta installed, see here
• Or use SandBox cluster rosetta conda environment.

Learning resources

• pyRosetta tutorials
• Colab Design
• RFDiffusion

Assignments

Take a structure of interest (with 2 or more protein chains):

1. Using pyRosetta, analyze energy between any two close residues of separate chains, output various energy terms.See 03.02-Analyzing-energy-between-residues.ipynb
2. (со звуздочкой) Using pyRosetta, take an arbitrary sequence of 10 amino acids. Try to do folding. Explore different lowest conformations depeding on the number of Monte-Carlo steps. Visualize results. See 04.01-Basic-Folding-Algorithm.ipynb
3. Use RFDiffusion to generate a new binder scaffold for the target protein. Use ProteinMPNN to generate the amino acid residues of the new binder. Use AlphaFold to check whether a complex similar to the original structure is formed.

Troubleshooting

• Consult with the seminar protocol/recording
• Ask questions in Slack