Back

Inferring Local Protein Structural Similarity from Sequence Alone

Ma, Z.; Herrera, J. E.; Bethel, N. P.; Jinich, A.

2025-11-27 bioinformatics
10.1101/2025.11.24.690129 bioRxiv
Show abstract

Detecting structural similarity at the local level between proteins is central to understanding function and evolution, yet most approaches require 3D models. In this work, we show that protein language models (pLMs), solely using sequence data as input, implicitly capture fine-grained structural signals that can be leveraged to identify such similarities. By mean-pooling residue embeddings over sliding windows and comparing them across proteins with cosine similarity, we find diagonal patterns that reflect locally aligned regions even without sequence identity. Building on this insight, we introduce a framework for detecting locally aligned structural regions directly from sequences, supporting the development of scalable methods for structural annotation and comparison.

Published in Journal of Chemical Information and Modeling (predicted rank #7) · training set

Matching journals

The top 3 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.