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

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 [23], 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) [35] , MSA-Transformer (multiple sequence alignment) [30] 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? (iii) 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 . * Equal Contribution † Corresponding author. Fajie designed the idea and led the research. Mingyang performed the research and led all experiments. Kevin provided important guidance for this research and worked on a part of paper writing. Jin performed experiments for the MSA generation. 36th Conference on Neural Information Processing Systems (NeurIPS 2022).