Alan Ashworth

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.

This paper designs a de novo protein fold that binds doxorubicin with high affinity through aromatic π-stacking, revealing a new 5-helix globular fold.

This paper develops a method to selectively kill cancer cells with TP53 mutations by using RNA-guided Cas12a2 to induce chromatin shredding through targeting cancer-specific transcripts.

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 paper sequences the mouse pseudoautosomal region, revealing its structure and evolutionary dynamics.

This paper identifies AVI-6451, an orally bioavailable inhibitor of SARS-CoV-2 Mac1 with once-daily efficacy in a mouse model.

The paper uses crystallographic ensembles to quantify conformational entropy changes in SARS-CoV-2 Macrodomain upon ligand binding, linking structural heterogeneity to binding thermodynamics.

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.

This study shows that CHIKV macrodomain catalytic activity affects virus replication and transmission in Aedes mosquitoes, with mutation-specific outcomes in different host contexts.

This study uses base-editing to inactivate a missense mutation in A20ZF7, enhancing CAR-T cell efficacy by reducing exhaustion and improving anti-tumor responses.

The paper uses single cell mass cytometry to identify protein modules associated with carboplatin resistance and sensitivity in ovarian cancer models.

This study characterizes AcrIF11, an ADP-ribosyltransferase that inhibits CRISPR-Cas systems with high potency and specificity, and shows its reversibility through macrodomain enzymes.

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.

This study identifies PCAHIT, a lncRNA linked to poor outcomes in prostate cancer, showing it promotes aggressive phenotypes by affecting steroid biosynthesis and immune response.

This study shows KDM5A and KDM5B regulate ERV expression and immune response by modulating KRAB-ZNF genes, with degradation of KDM5A causing rapid ERV activation.

This paper designs drug-binding proteins with low nanomolar affinity and predictable specificity using computational methods, validated by experimental measurements and structural analysis.

This paper compares two CreERT2 mice, showing Itga8-CreERT2 avoids a lethal intestinal phenotype seen with Myh11-CreERT2 when knocking out Srf.

This study uses 5-hydroxymethyl cytosine (5hmC) profiles in plasma cell-free DNA to detect multiple cancers with high accuracy using machine learning.

This paper develops a non-viral CRISPR-Cas9 system for precise genome editing in human T cells, enabling therapeutic reprogramming of cell function and specificity.