EvoProtGrad
A Python package for directed evolution on a protein sequence with gradient-based discrete Markov chain monte carlo (MCMC). Users are able to compose their custom protein models that map sequence to function with various pretrained models, including protein language models (PLMs), to guide and constrain search. The library is designed to natively integrate with 🤗 HuggingFace and supports PLMs from the transformers library.
The underlying search technique is based on a variant of discrete MCMC that uses gradients of a differentiable compositional target function to rapidly explore a protein's fitness landscape in sequence space.
We allow users to compose their own custom target function for MCMC by leveraging the Product of Experts MCMC paradigm.
Each model is an "expert" that contributes its own knowledge about the protein's fitness landscape to the overall target function.
Our MCMC sampler is designed to be more efficient and effective than brute force and random search while maintaining most of the generality and flexibility.
See our publication and our documentation for more details.
Installation
EvoProtGrad is available on PyPI and can be installed with pip:
pip install evo_prot_grad
If you wish to run tests or register a new expert model with EvoProtGrad, please clone this repo and install in editable mode as follows:
git clone https://github.com/NREL/EvoProtGrad.git
cd EvoProtGrad
pip install -e .
Basic Usage
Create a ProtBERT
expert from a pretrained HuggingFace protein language model (PLM) using evo_prot_grad.get_expert
:
import evo_prot_grad
prot_bert_expert = evo_prot_grad.get_expert('bert', temperature = 1.0)
The default BERT-style PLM in EvoProtGrad
is Rostlab/prot_bert
. Normally, we would need to also specify the model and tokenizer. When using a default PLM expert, we automatically pull these from the HuggingFace Hub. The temperature parameter rescales the expert scores and can be used to trade off the importance of different experts. For masked language models like prot_bert
, we score variant sequences with the sum of amino acid log probabilities by default.
Then, create an instance of DirectedEvolution
and run the search, returning a list of the best variant per Markov chain (as measured by the prot_bert
expert):
variants, scores = evo_prot_grad.DirectedEvolution(
wt_fasta = 'test/gfp.fasta',
output = 'best',
experts = [prot_bert_expert],
parallel_chains = 1,
n_steps = 20,
max_mutations = 10,
verbose = True
)()
We provide a few experts in evo_prot_grad/experts
that you can use out of the box, such as:
Protein Language Models (PLMs)
bert
, BERT-style PLMs, default: Rostlab/prot_bert
causallm
, CausalLM-style PLMs, default: lightonai/RITA_s
esm
, ESM-style PLMs, default: facebook/esm2_t6_8M_UR50D
Potts models
and an generic expert for supervised downstream regression models
onehot_downstream_regression
See demo.ipynb
to get started right away in a Jupyter notebook.
Citation
If you use EvoProtGrad in your research, please cite the following publication:
@article{emami2023plug,
title={Plug \& play directed evolution of proteins with gradient-based discrete MCMC},
author={Emami, Patrick and Perreault, Aidan and Law, Jeffrey and Biagioni, David and John, Peter St},
journal={Machine Learning: Science and Technology},
volume={4},
number={2},
pages={025014},
year={2023},
publisher={IOP Publishing}
}