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While the vast majority of well-structured single protein chains can now be predicted to high accuracy due to the recent AlphaFold [1] model, the prediction of multi-chain protein complexes remains a challenge in many cases. 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 [2]) we achieve at least medium accuracy (DockQ [3]≥0.49) on 14 targets and high accuracy (DockQ≥0.8) on 6 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 [2]). We also predict structures for a large dataset of 4,433 recent protein complexes, from which we score all non-redundant interfaces with low template identity. For heteromeric interfaces we successfully predict the interface (DockQ≥0.23) in 67% of cases, and produce high accuracy predictions (DockQ≥0.8) in 23% of cases, an improvement of +25 and +11 percentage points over the flexible linker modification of AlphaFold [4] respectively. For homomeric interfaces we successfully predict the interface in 69% of cases, and produce high accuracy predictions in 34% of cases, an improvement of +5 percentage points in both instances.

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We describe the operation and improvement of AlphaFold, the system that was entered by the team AlphaFold2 to the "human" category in the 14th Critical Assessment of Protein Structure Prediction (CASP14). The AlphaFold system entered in CASP14 is entirely different to the one entered in CASP13. It used a novel end-toend deep neural network trained to produce protein structures from amino acid sequence, multiple sequence alignments, and homologous proteins. In the assessors' ranking by summed z scores (>2.0), AlphaFold scored 244.0 compared to 90.8 by the next best group. The predictions made by AlphaFold had a median domain GDT_TS of 92.4; this is the first time that this level of average accuracy has been achieved during CASP, especially on the more difficult Free Modeling targets, and represents a significant improvement in the state of the art in protein structure prediction. We reported how AlphaFold was run as a human team during CASP14 and improved such that it now achieves an equivalent level of performance without intervention, opening the door to highly accurate large-scale structure prediction.

We present a method for combining multiagent communication and traditional datadriven approaches to natural language learning, with an end goal of teaching agents to communicate with humans in natural language. Our starting point is a language model that has been trained on generic, not task-specific language data. We then place this model in a multi-agent self-play environment that generates task-specific rewards used to adapt or modulate the model, turning it into a taskconditional language model. We introduce a new way for combining the two types of learning based on the idea of reranking language model samples, and show that this method outperforms others in communicating with humans in a visual referential communication task. Finally, we present a taxonomy of different types of language drift that can occur alongside a set of measures to detect them.