esm/cookbook/tutorials/README.md

ESM Tutorial Notebooks

Tutorial notebooks are the best way to get hands-on with ESM models! Use the notebooks to explore model capabilities, learn workflows that can be applied to your own data, and learn how to interpret model outputs.

ESMC

ESMC is a protein language model that embeds sequences into rich numerical representations. Use it for analyzing, classifying, comparing, and interpreting proteins.

Notebook	Colab Notebook	Description
Embedding sequences with ESMC	embed.ipynb	Embed protein sequences and explore how different transformer layers encode structural and functional information.
Zero-shot entropy and mutation analysis	esmc_mutation_scoring.ipynb	Compute per-position entropy and log-likelihood ratios to identify constrained vs. mutation-tolerant sites.
Layer sweep for enzyme function classification	esmc_layer_sweep.ipynb	Learn how to sweep all layers to find which one is best using enzyme classification as a task.
Fine-tuning ESMC	esmc_finetune.ipynb	Fine-tune a classification or regression head for your dataset on top of ESMC using Parameter Efficient Fine-tuning (PEFT)

Interpretable features through Sparse Autoencoders (SAEs)

Notebook	Colab Notebook	Description
Understanding proteins with SAE features	esmc_sae_feature_interpretation.ipynb	Extract and visualize sparse autoencoder features, rank by peak activation and prevalence, and map activations onto 3D structure.

ESMFold2

ESMFold2 predicts 3D protein structure from sequence, including DNA/RNA and small molecules.

Notebook	Colab Notebook	Description
Folding with ESMFold2	esmfold2.ipynb	Fold proteins in combination with DNA, RNA and small-molecule ligands.
Binder design	binder_design.ipynb	Design antibodies and minibinders with high hit rates. Implements the protocol featured in our paper, which produced binders exhibiting nanomolar affinity, target specificity, and functional activity in laboratory assays.

ESM3

ESM3 is a generative model that reasons jointly over protein sequence, structure, and function. Use it for designing new proteins or editing existing ones.

Notebook	Colab Notebook	Description
Understanding the ESMProtein class	esmprotein.ipynb	Get familiar with how ESM3 represents proteins.
Generating proteins with ESM3	esm3_generate.ipynb	Learn how to scaffold a functional motif, edit secondary structure, and guide design using solvent exposure.
Designing a novel GFP with ESM3	gfp_design.ipynb	Walk through the exact prompting strategy used to design a novel fluorescent protein with no close natural relatives.
Guided generation with ESM3	esm3_guided_generation.ipynb	Add scoring functions into the generation process, such as structural quality, sequence constraints, or other properties.