Protein complex prediction with AlphaFold-Multimer

🤖 Plain-English Summary

While the vast majority of well-structured single protein chains can now be predicted to high accuracy due to the recent AlphaFold model, the prediction of multi-chain protein complexes remains a challenge in many cases. For heteromeric interfaces we successfully predict the interface (DockQ ≥ 0.23) in 70% of cases, and produce high accuracy predictions (DockQ ≥ 0.8) in 26% of cases, an improvement of +27 and +14 percentage points over the flexible linker modification of AlphaFold respectively.

🔑 Key Findings

• In this work, we demonstrate that an AlphaFold model trained specifically for multimeric inputs of known stoichiometry, which we call AlphaFold-Multimer, significantly increases accuracy of predicted multimeric interfaces over input-adapted single-chain AlphaFold while maintaining high intra-chain accuracy.
• On a benchmark dataset of 17 heterodimer proteins without templates (introduced in ) we achieve at least medium accuracy (DockQ ≥ 0.49) on 13 targets and high accuracy (DockQ ≥ 0.8) on 7 targets, compared to 9 targets of at least medium accuracy and 4 of high accuracy for the previous state of the art system (an AlphaFold-based system from ).
• We also predict structures for a large dataset of 4,446 recent protein complexes, from which we score all non-redundant interfaces with low template identity.

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