Biology subjects

Feller, A. L.

Publications and source records attributed to Feller, A. L..

3 recordsLinked to original sources

bioRxiv2026

Validation and analysis of 12,000 AI-driven CAR-T designs in the Bits to Binders competition

Artificial intelligence (AI) methods for proteins have advanced rapidly, improving structure prediction and design, particularly for de novo binders. However, most evaluations emphasize binding affinity rather than higher-order biological function. We present Bits to Binders, a global competition benchmarking de novo binder design in the context of chimeric antigen receptor (CAR) T cells. Teams from 42 countries submitted 12,000 designs of 80-amino acid binders targeting human CD20 as CAR binding domains. Designs were screened by pooled CAR-T proliferation, identifying 707 designs exhibiting significant CD20-specific enrichment, with team hit rates from 0.6% to 38.4%. Top-performing candidates were validated as individual constructs, measuring CD20-specific proliferation, expansion, cytokine production, and targeted cell lysis. We identified common design methodologies and factors correlated with DNA synthesis, expression, and target-specific T cell activation which nearly double the success rates when applied as a retrospective filter. We release this dataset as an open resource, with practical recommendations to support more effective AI-driven binder design.

bioinformatics↗

bioRxiv2026

PeptideMTR: Scaling SMILES-Based Language Models for Therapeutic Peptide Engineering

Therapeutic peptides occupy a unique middle ground in drug discovery, offering the high specificity of protein interactions with the chemical diversity of small molecules, yet they currently fall in a computational blind spot. Existing foundation models cannot handle them effectively: protein models are restricted to natural amino acids, while chemical models struggle to process large, polymer-like sequences. This disconnect has forced the field to rely on static chemical descriptors that fail to capture subtle chemical details or on complex multi-embedding pipelines that are custom tailored to specific datasets. To bridge this gap, we present PeptideCLM-2, a suite of chemical language models trained on over 100 million molecules to natively represent complex peptide chemistry. This modeling approach expands the available toolkit of machine learning models for therapeutic peptides. Benchmarking results show strong performance versus prior methods for predicting development endpoints including membrane diffusion, biological function, and half life.

bioinformatics↗

bioRxiv2024

Peptide-specific chemical language model successfully predicts membrane diffusion of cyclic peptides

Language modeling applied to biological data has significantly advanced the prediction of membrane penetration for small molecule drugs and natural peptides. However, accurately predicting membrane diffusion for peptides with pharmacologically relevant modifications remains a substantial challenge. Here, we introduce PeptideCLM, a peptide-focused chemical language model capable of encoding peptides with chemical modifications, unnatural or non-canonical amino acids, and cyclizations. We assess this model by predicting membrane diffusion of cyclic peptides, demonstrating greater predictive power than existing chemical language models. Our model is versatile and can be extended beyond membrane diffusion predictions to other target values. Its advantages include the ability to model macromolecules using chemical string notation, a largely unexplored domain, and a simple, flexible architecture that allows for adaptation to any peptide or other macromolecule dataset.

bioinformatics↗