arXiv:2606. 02629v1 Announce Type: cross Abstract: Protein-protein interactions (PPIs) are essential for many biological processes.
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.
arXiv:2512. 15133v3 Announce Type: replace-cross Abstract: Proteins inherently possess a consistent sequence-structure duality.
arXiv:2606. 27440v1 Announce Type: new Abstract: Foundation models for structural biology have achieved remarkable performance in predicting biomolecular structure and show promise for the design of proteins and small molecules.
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.
The paper introduces a multimodal framework that learns subcellularly resolved cell embeddings by integrating RNA expression profiles, protein sequence representations, and protein structural information. It uses a cross‑attention architecture to model interactions across distinct subcellular compartments, producing embeddings that capture both molecular expression patterns and functional protein properties. This approach is presented as the first to jointly incorporate transcriptomic data, protein sequences, and structural knowledge within a unified cross‑modal learning paradigm.
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...
The paper introduces a multimodal framework that learns subcellularly resolved cell embeddings by integrating RNA expression profiles, protein sequence representations, and protein structural information using a cross‑attention architecture. This approach models interactions within distinct subcellular compartments, producing fine‑grained embeddings that capture both molecular expression patterns and functional protein properties. It is presented as the first method to jointly incorporate transcriptomic data, sequence, and structural knowledge for subcellularly resolved cell representation.
SimpleDesign is a single-stage, end-to-end model for joint protein sequence and structure design that eliminates the need for multi-stage training. It combines discrete cross-entropy for sequences with a regression objective for structures, using a Mixture-of-Transformer architecture to handle modality-specific processing while maintaining global self-attention. Trained on over 2 million sequence-structure pairs, SimpleDesign achieves strong performance on co-design and unconditional generation benchmarks.
arXiv:2607. 01627v1 Announce Type: cross Abstract: Accurate protein-protein interaction (PPI) prediction is central to functional genomics, disease mechanism discovery, and drug development.
arXiv:2608.21367v1 Announce Type: cross Abstract: Protein-peptide interactions are central to cellular regulation and peptide-based drug discovery, yet existing computational methods mainly focus on...
The paper introduces a method that uses orthogonal projection to remove the influence of known biochemical features from protein language model (PLM) embeddings, allowing the authors to assess how much these features contribute to protein fitness predictions. By applying this technique to high‑order and interaction effects, they demonstrate that eliminating these interpretable features reduces downstream classifier performance, indicating that PLM embeddings encode patterns correlated with biochemical properties. The authors also show that these biochemical features explain a substantial portion of the variance in the classifier’s predictions, suggesting that PLM embeddings capture biologically relevant information.
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.