Yagmur Umay Doruk

Large scale prospective evaluation of co-folding across hundreds of Mac1-ligand complexes and three virtual screens

On 489 evaluable new Mac1 complexes, AlphaFold3, Chai-1 and Boltz-2 placed over half of ligands within 2 Å, but on docking hit-lists AF3 and Boltz-2 added little over docking.

Toward a Random Background for Ligand Optimization

This study systematically evaluates the effectiveness of random small perturbations in ligand optimization, finding 11.2% of analogs improved potency by ≥10-fold but often had worse pharmacokinetics.

The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2

This study identifies Mac1 as a therapeutic target for SARS-CoV-2 and demonstrates that AVI-4206, a small molecule inhibitor, reduces viral replication and improves survival in an animal model.

Extensive exploration of structure activity relationships for the SARS-CoV-2 macrodomain from shape-based fragment merging and active learning

Shape-based fragment merging (FrankenROCS) with Thompson sampling over 22 billion molecules found neutral SARS-CoV-2 macrodomain inhibitors; analogs reached single-digit micromolar IC50, backed by 137 crystal structures.