The paper introduces a scalable method to interpret sparse autoencoder (SAE) features in the ESM-2 protein language model by leveraging geometrically inspired features of the protein α‑carbon backbone. Across 8M layers of ESM-2, a false discovery rate–controlled analysis shows that local geometry is significantly associated with many SAE features, revealing substructure within known biological labels and enabling annotation of unannotated metagenomic proteins. Ablation experiments demonstrate that removing these geometric features shifts ESM-2’s predicted contact maps toward the descriptor, linking mechanistic interpretability with structural biology.
By Siddharth Setlur, Djordje Mihajlovic, Darrick Lee
ProtLingo is a protein language modeling framework that enhances a pretrained single‑sequence Transformer backbone with conditional local memory and sparse expert routing. It maps residue representations into discrete codes, composes local windows into latent N‑gram addresses, and retrieves reusable residual signals for recurring sequence contexts. The model also converts selected feed‑forward blocks into sparse Mixture‑of‑Experts layers, allowing residue‑dependent computation while activating only a subset of parameters, achieving competitive performance on protein fitness prediction, FLIP benchmarks, and supervised contact prediction with a 150M‑parameter backbone.
By Mingrui Li, Sixian Shen, Minzhang Li, Ruiyi Zhang, Kexin Zhang, Jiakai Zhang, Jingyi Yu
arXiv:2609.37675v1 Announce Type: new
Abstract: Protein Language Models (PLMs) have made remarkable progress following scaling laws established in natural language processing across sequence- and str...
By Biswajit Banerjee, Claudia Alvarez Carreno, Anton S. Petrov
arXiv:2605. 01625v3 Announce Type: replace Abstract: Proteins are inherently multiscale physical systems whose functional properties emerge from coordinated structural organization across multiple spatial resolutions, ranging from atomic interactions to global fold topology.
By Viet Thanh Duy Nguyen, John K. Johnstone, Truong-Son Hy
Protein language models (PLMs) have transferred the latest advances from natural language processing to computational biology. These models, trained on large corpora of protein sequence data, are widely used to translate amino acid sequences into latent-space embeddings, ready for use in diverse downstream tasks (DTs).
arXiv:2608. 12090v1 Announce Type: new Abstract: Protein language models (PLMs) have transferred the latest advances from natural language processing to computational biology.
By Roman Joeres, Ilya Senatorov, Olga V. Kalinina