Papers › Exploring evolution-aware & -free protein language models as protein function predictors

Exploring evolution-aware & -free protein language models as protein function predictors

14 Jun 2022arXiv:2206.06583archive 2025-07-28

Mingyang Hu, Fajie Yuan, Kevin K. Yang, Fusong Ju, Jin Su, Hui Wang, Fei Yang, Qiuyang Ding

Large-scale Protein Language Models (PLMs) have improved performance in protein prediction tasks, ranging from 3D structure prediction to various function predictions. In particular, AlphaFold, a ground-breaking AI system, could potentially reshape structural biology. However, the utility of the PLM module in AlphaFold, Evoformer, has not been explored beyond structure prediction. In this paper, we investigate the representation ability of three popular PLMs: ESM-1b (single sequence), MSA-Transformer (multiple sequence alignment) and Evoformer (structural), with a special focus on Evoformer. Specifically, we aim to answer the following key questions: (i) Does the Evoformer trained as part of AlphaFold produce representations amenable to predicting protein function? (ii) If yes, can Evoformer replace ESM-1b and MSA-Transformer? (ii) How much do these PLMs rely on evolution-related protein data? In this regard, are they complementary to each other? We compare these models by empirical study along with new insights and conclusions. All code and datasets for reproducibility are available at https://github.com/elttaes/Revisiting-PLMs.

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apc elttaes/revisiting-plms/ESM-1b_Pretrain/esm/modules.py official repository ran fingerprinted MIT (permissive) · f6701ae421cbe0d4 · report
gelu elttaes/revisiting-plms/ESM-1b_Pretrain/esm/modules.py official repository ran fingerprinted MIT (permissive) · 2e7bd6c4ccd1ed68 · report
symmetrize elttaes/revisiting-plms/ESM-1b_Pretrain/esm/modules.py official repository ran · violated contract fingerprinted MIT (permissive) · b385be9826c4a8b3 · report
aa2num elttaes/revisiting-plms/ESM-MSA/GREMLIN_tensorflow.py official repository unverified MIT (permissive) · b5f6e8201d45514b · report
calc_neff elttaes/revisiting-plms/ESM-MSA/af2_eval.py official repository unverified MIT (permissive) · 95cfb6fa75b827cc · report
filt_gaps elttaes/revisiting-plms/ESM-MSA/GREMLIN_tensorflow.py official repository unverified MIT (permissive) · 4ef9ac2f182847f2 · report
generate_coordinates elttaes/revisiting-plms/ESM-MSA/draw.py official repository unverified MIT (permissive) · 32b11da71f634b4a · report
parse_fasta elttaes/revisiting-plms/ESM-MSA/GREMLIN_tensorflow.py official repository unverified MIT (permissive) · be03e131ebf978b6 · report
reduce_loss elttaes/revisiting-plms/ESM-1b_Pretrain/DDP_train_1b.py official repository unverified MIT (permissive) · 7bbb1a6e077ff43b · report

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Multiple Sequence AlignmentPrediction

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AlphaFold

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