Biophysics-based protein language models for protein engineering DOI Creative Commons
Sam Gelman,

Bryce Johnson,

Chase R. Freschlin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 17, 2024

Protein language models trained on evolutionary data have emerged as powerful tools for predictive problems involving protein sequence, structure, and function. However, these overlook decades of research into biophysical factors governing We propose Mutational Effect Transfer Learning (METL), a model framework that unites advanced machine learning modeling. Using the METL framework, we pretrain transformer-based neural networks simulation to capture fundamental relationships between energetics. finetune experimental sequence-function harness signals apply them when predicting properties like thermostability, catalytic activity, fluorescence. excels in challenging engineering tasks generalizing from small training sets position extrapolation, although existing methods train remain many types assays. demonstrate METL's ability design functional green fluorescent variants only 64 examples, showcasing potential biophysics-based engineering.

Language: Английский

Biophysics-based protein language models for protein engineering DOI Creative Commons
Sam Gelman,

Bryce Johnson,

Chase R. Freschlin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 17, 2024

Protein language models trained on evolutionary data have emerged as powerful tools for predictive problems involving protein sequence, structure, and function. However, these overlook decades of research into biophysical factors governing We propose Mutational Effect Transfer Learning (METL), a model framework that unites advanced machine learning modeling. Using the METL framework, we pretrain transformer-based neural networks simulation to capture fundamental relationships between energetics. finetune experimental sequence-function harness signals apply them when predicting properties like thermostability, catalytic activity, fluorescence. excels in challenging engineering tasks generalizing from small training sets position extrapolation, although existing methods train remain many types assays. demonstrate METL's ability design functional green fluorescent variants only 64 examples, showcasing potential biophysics-based engineering.

Language: Английский

Citations

11