Morgan E. Diolaiti

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.

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

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

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

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.

The paper develops an ODE model of PARP1 inhibition, identifies key parameters through sensitivity analysis, and discovers GSPT2 as a biomarker linked to cancer patient outcomes.