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

Assignments

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

Using pyRosetta, analyze energy between any two close residues of separate chains, output various energy terms.See 03.02-Analyzing-energy-between-residues.ipynb
(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
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