Evolutionary-scale prediction of atomic-level protein structure with a language model

Science. 2023 Mar 17;379(6637):1123-1130. doi: 10.1126/science.ade2574. Epub 2023 Mar 16.

Abstract

Recent advances in machine learning have leveraged evolutionary information in multiple sequence alignments to predict protein structure. We demonstrate direct inference of full atomic-level protein structure from primary sequence using a large language model. As language models of protein sequences are scaled up to 15 billion parameters, an atomic-resolution picture of protein structure emerges in the learned representations. This results in an order-of-magnitude acceleration of high-resolution structure prediction, which enables large-scale structural characterization of metagenomic proteins. We apply this capability to construct the ESM Metagenomic Atlas by predicting structures for >617 million metagenomic protein sequences, including >225 million that are predicted with high confidence, which gives a view into the vast breadth and diversity of natural proteins.

MeSH terms

  • Amino Acid Sequence
  • Evolution, Molecular*
  • Machine Learning*
  • Protein Conformation
  • Proteins* / chemistry
  • Sequence Analysis, Protein*

Substances

  • Proteins