Biology subjects

Koob, J.

Publications and source records attributed to Koob, J..

2 recordsLinked to original sources

bioRxiv2026

Reliable and Efficient Agentic Protein Design with Toolset Harnessing

Computational protein design workflows require the orchestration of multiple tools, data formats, and analysis steps that are often fragmented. Here, we introduce Chaperone, a lightweight and customizable framework that enables seamless integration of RFdiffusion3 (RFD3) with downstream sequence design, structure prediction, and evaluation tools, including ProteinMPNN, AlphaFold3 (AF3), and more than 50 other protein design tools. By combining a programmable agent-friendly interface with parallelized execution on high-performance computing systems, Chaperone as a harness enables rapid iteration and scalable exploration of complex protein design workflows. Across an evaluation of nine biomolecular design tasks, we find using Chaperone reduces total token usage relative to baseline agents by 86% and GPU costs by 64%, while increasing the overall computational design pass rate. We demonstrate Chaperones utility for large-scale design-space exploration through a two-week end-to-end small-molecule binder design campaign, yielding low nanomolar binders to cortisol zero shot. We further demonstrate its versatility across distinct design challenges, including the design of a symmetric 12-subunit self-assembly nanoparticle and a linker that mediates interactions between C2- and D3-symmetric protein complexes to form crystalline assemblies. Together, these results demonstrate how agent harnesses built around standardized tool interfaces can substantially improve the efficiency and success of complex, long-horizon agentic design workflows in biology. We make Chaperone freely available to the community on GitHub: https://github.com/RosettaCommons/chaperone.

biochemistry↗

bioRxiv2022

Programmable eukaryotic protein expression with RNA sensors

The diversity of cell types and states can be scalably measured and defined by expressed RNA transcripts. However, approaches to programmably sense and respond to the presence of specific RNAs within living biological systems with high sensitivity are lacking. RNA sensors that gate expression of reporter or cargo genes would have diverse applications for basic biology, diagnostics and therapeutics by enabling cell-state specific control of transgene expression. Here, we engineer a novel programmable RNA-sensing technology, Reprogrammable ADAR Sensors (RADARS), which leverages RNA editing by adenosine deaminases acting on RNA (ADAR) to gate translation of a protein payload on the presence of endogenous RNA transcripts. In mammalian cells, we engineer RADARS with diverse payloads, including luciferase and fluorescent proteins, with up to 164-fold activation and quantitative detection in the presence of target RNAs. We show RADARS are functional either expressed from DNA or as synthetic mRNA. Importantly, RADARS can function with endogenous cellular ADAR. We apply RADARS to multiple contexts, including RNA-sensing induced cell death via caspases, cell type identification, and in vivo control of synthetic mRNA translation, demonstrating RADARS as a tool with significant potential for gene and cell therapy, synthetic biology, and biomedical research. One Sentence SummaryA new technology utilizing ADAR mediated RNA-editing enables robust reprogrammable protein expression based on target RNA transcripts in mammalian cells, leading to broad applications in basic science research, cell engineering, and gene therapy.

genomics↗