The ability to generate proteins with desired functions is a central goal of computational biology. Although natural language can express diverse design objectives, existing protein generation methods...
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.
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.
arXiv:2505. 20346v3 Announce Type: replace-cross Abstract: Function-guided protein design is a crucial task with significant applications in drug discovery and enzyme engineering.
Large protein language models provide a powerful framework for learning sequence-function relationships and guiding experimental design. However, architectural improvements are underexplored, especial...
SymFold introduces a symmetric dual‑path architecture that combines protein language models (PLMs) and multimodal protein language models (MPLMs) to iteratively guide protein sequence generation for inverse folding. By leveraging pretrained sequence evolution knowledge from PLMs and structural knowledge from MPLMs, the method improves upon the traditional serial pipeline where structure encoders produce coarse sequences refined by PLMs. Experiments on standard inverse‑folding benchmarks show state‑of‑the‑art performance, and ablation studies confirm the effectiveness of the symmetric design.
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.
The paper introduces a flexible sampling technique for masked language models (MLMs) called stochastic beam search, which leverages MLMs’ efficiency in evaluating the pseudo‑perplexity of a sequence’s 1‑edit neighborhood. This method reframes generation as whole‑sequence evaluation, allowing guidance across multiple optimization objectives. Extensive in‑silico and in‑vitro tests on antibody therapeutics demonstrate that the sampling strategy significantly influences outcomes, highlighting the need for further research in this area.
arXiv:2606. 02386v1 Announce Type: new Abstract: Protein language models (PLMs) are passive oracles: they generate sequences in a single forward pass with no mechanism to consult external biophysical feedback or redirect generation when a candidate violates thermodynamic or structural constraints.
ProTok introduces a unified protein tokenizer that maps protein sequence, structure, and functional annotations into a single modular discrete vocabulary using product quantization with per-modality codebook groups and modality dropout. The tokenizer supports flexible inference from any subset of modalities without retraining and achieves top performance on seven StructTokenBench benchmarks, with high reconstruction accuracy (0.939 lDDT on CATH 4.2) and superior zero‑shot functional retrieval. Additionally, a compact language model trained on ProTok tokens can jointly generate backbone and sequence, yielding a higher proportion of designable backbones compared to a GeoBPE baseline.
arXiv:2609.05818v1 Announce Type: new Abstract: We introduce ABLE, a benchmark for evaluating LLM agents' ability to use biological AI models (BAIMs), such as ProteinMPNN and AlphaFold3, in dual-use...
arXiv:2505.23862v2 Announce Type: replace-cross Abstract: The mRNA optimization is essential for mRNA vaccines, therapies, and industrial protein production. Based on current explorations, an ideal o...