arXiv Machine Learning
Oct 12

Designing Protein Structures from Natural Language

The paper introduces Prompteina, an all‑atom protein structure generation model that accepts natural‑language descriptions of desired structural and functional properties, similar to text‑to‑image systems. It is trained on a large paired dataset of 1.8 million protein structures and over 50 million captions, and fine‑tuned from the Proteina‑Complexa model to align residues with textual cues. Prompteina outperforms existing baselines on most structural metrics, improves binder design performance, and experimentally validates nine new binders for the GM2A target.

By Joseph Lee, Yanjing Li, Bo Qiang, Gregory Lau, Allyson Ettinger, Noah A. Smith, Rory Donovan-Maiye, David Baker, Hanna Hajishirzi, Pang Wei Koh
arXiv Machine Learning
Oct 15

ProtModernBERT: Compute-Efficient Protein Language Modeling

ProtModernBERT is a modernized BERT-style protein language model that reduces training cost by incorporating architectural refinements, achieving performance comparable to larger models while cutting pre‑training FLOPs by 80‑90%. The authors benchmark ProtModernBERT against ProtBert, Amplify, and ESM2 on supervised structural tasks and a zero‑shot functional benchmark, showing it matches or closely tracks Amplify‑120M and ProtBert. Their cluster‑based validation and random‑init experiments reveal that modern architectural components provide stronger inductive biases than parameter count in low‑compute regimes.

By Alberto Mart\'inez, Natalia Flechas Manrique, Lloren\c{c} Espinosa-Portal\'es, Luc Andrea
arXiv Machine Learning
Oct 3

Generative modeling of intrinsically disordered protein regions by reinforcing sparse autoencoder features

The paper introduces IDiom, an autoregressive protein language model trained on a large dataset of intrinsically disordered protein regions (IDRs) from AlphaFold, and demonstrates that it can generate sequences matching natural IDR composition, motifs, and disorder. It further presents RL‑SAE, a reinforcement learning approach that uses sparse autoencoder features to steer generation toward specific functional patterns, achieving high activation of targeted features and improved predicted subcellular localization and transcriptional activity. The combination of IDiom and RL‑SAE allows interpretable, composable IDR design by explicitly controlling function‑associated sequence features.

By Jason X. Liu, Sebastian Ibarraran, Frank Hu, Soojung Yang, Xinyu A. Feng, Abigail Park, Anagha Aneesh, Lacramioara Bintu, Alexander R. Dunn, Grant M. Rotskoff