Ouyang-Zhang, J.; Gong, C.; Zhao, Y.; Krähenbühl, P.; Klivans, A. R.; Diaz, D. J.

Protein language models, like the popular ESM2, are widely used tools for extracting evolution-based protein representations and have achieved significant success on downstream biological tasks. Representations based on sequence and structure models, however, show significant performance differences depending on the downstream task. A major open problem is to obtain representations that best capture both the evolutionary and structural properties of proteins in general. Here we introduce Implicit Structure Model (ISM), a sequence-only input model with structurally-enriched representations that outperforms state-of-the-art sequence models on several well-studied benchmarks including mutation stability assessment and structure prediction. Our key innovations are a microenvironment-based autoencoder for generating structure tokens and a self-supervised training objective that distills these tokens into ESM2\'s pre-trained model. We have made ISM\'s structure-enriched weights easily available: integrating ISM into any application using ESM2 requires changing only a single line of code. Our code is available at https://github.com/jozhang97/ISM.