AbbVie (United States)

PharmaDiff turns a 3D pharmacophore hypothesis into an atom-level subgraph and injects it as a condition into diffusion-based generation, producing 3D molecules that follow the prescribed spatial arrangement. Across 250 pharmacophore conditions drawn from the GEOM-Drugs test set it reaches a mean match score of 0.8964 and a perfect match rate of 0.6990, above PGMG, TransPharmer, REINVENT4, ShEPhERD and PhoreGen; its average docking scores on four targets also beat DiffSBDD, which needs the protein structure, though its PoseBusters pass rate is below ShEPhERD and PhoreGen.

PharmaDiff turns a 3D pharmacophore hypothesis into an atom-level subgraph and injects it as a condition into diffusion-based generation, producing 3D molecules that follow the prescribed spatial arrangement. Across 250 pharmacophore conditions drawn from the GEOM-Drugs test set it reaches a mean match score of 0.8964 and a perfect match rate of 0.6990, above PGMG, TransPharmer, REINVENT4, ShEPhERD and PhoreGen; its average docking scores on four targets also beat DiffSBDD, which needs the protein structure, though its PoseBusters pass rate is below ShEPhERD and PhoreGen.

Ranking polymorphs of molecular crystals by thermodynamic stability has relied on the Einstein crystal method (ECM), which must sample a separate chain of overlapping alchemical states for every polymorph, a cost that grows unmanageable across large crystal landscapes. This work hands the mapping in targeted free-energy perturbation to a normalizing flow: the model reversibly transforms molecular-dynamics supercell configurations onto an analytical reference distribution, and targeted Bennett acceptance ratio (tBAR) reweighting then yields lattice free energies. On succinic acid, Veliparib and Mivebresib the estimates agree with ECM, handle supercells of up to about 3×10³ degrees of freedom, and take on average roughly one over 2.5 of the ECM time.

Ranking polymorphs of molecular crystals by thermodynamic stability has relied on the Einstein crystal method (ECM), which must sample a separate chain of overlapping alchemical states for every polymorph, a cost that grows unmanageable across large crystal landscapes. This work hands the mapping in targeted free-energy perturbation to a normalizing flow: the model reversibly transforms molecular-dynamics supercell configurations onto an analytical reference distribution, and targeted Bennett acceptance ratio (tBAR) reweighting then yields lattice free energies. On succinic acid, Veliparib and Mivebresib the estimates agree with ECM, handle supercells of up to about 3×10³ degrees of freedom, and take on average roughly one over 2.5 of the ECM time.