#36 · Structural bio & protein design

Computational and experimental design of regulatory DNA and enhancer target selection

The common thread is computational and experimental engineering of regulatory DNA and the proteins that act on it. RegDesign-Bench provides a standardized benchmark for comparing methods that design cell-type-specific cis-regulatory DNA, establishing a common evaluation basis for this design task. Separately, synthetic activators are designed with AlphaFold3 guidance, with more than 300 coactivator-binding proteins screened in mammalian cells for programmable gene expression. The SPIE-seq enhancer insertion screen across 724 clonal lines tests the RbP model, which allocates enhancer output among promoters by distance, contact and intrinsic factors. What is new is direct experimental testing of predictive allocation rules for enhancer target selection, alongside structure-guided design of activator proteins. The items are heterogeneous: only the enhancer study tests a mechanistic model of regulatory allocation, while the others address design and benchmarking.