Herrera, J. E. | Search bioRxiv

bioRxiv2025

Inferring Local Protein Structural Similarity from Sequence Alone

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.

bioinformatics↗

bioRxiv2024

The Protein Language Visualizer: Sequence Similarity Networks for the Era of Language Models

AO_SCPLOWBSTRACTC_SCPLOWThe era of modern AI-driven representations of proteins is here, and moving fast, yet tools for their intuitive visualization and exploration lag behind. Sequence Similarity Networks (SSNs) have long filled this role for alignment-based methods, providing simple but widely adopted platforms for grouping proteins by homology. Building on this foundation, we present the Protein Language Visualizer (PLVis), a modular framework that applies existing pre-trained protein language model (pLM) embeddings, dimensionality reduction, and clustering to generate interactive maps of protein relationships. The central contribution is the PLVis Repository, an online resource where thousands of reference proteomes can be compared and annotated through an accessible, interactive interface, much like SSNs became impactful not for their technical novelty but for their broad usability. We first validate that well-separated clusters in PLVis reliably capture homology information, while emphasizing caution when interpreting central "fuzzy" regions. We then illustrate the value of PLVis through case studies spanning individual protein families to full proteome comparisons across Mycobacterium and Plasmodium species. By combining methodological clarity with broad accessibility, the PLVis Repository provides a low-barrier platform for exploring proteomes through the lens of language models.

bioinformatics↗