Pharmacophore-guided de novo drug design with diffusion bridge
This work addresses drug discovery by improving molecule generation for specific biological targets, though it appears incremental as it builds on existing diffusion methods with a pharmacophore focus.
The authors tackled the problem of generating bioactive drug molecules by proposing PharmacoBridge, a pharmacophore-guided de novo design approach using diffusion bridge, which generates drug candidates with high binding affinity to protein targets.
De novo design of bioactive drug molecules with potential to treat desired biological targets is a profound task in the drug discovery process. Existing approaches tend to leverage the pocket structure of the target protein to condition the molecule generation. However, even the pocket area of the target protein may contain redundant information since not all atoms in the pocket is responsible for the interaction with the ligand. In this work, we propose PharmacoBridge, a phamacophore-guided de novo design approach to generate drug candidates inducing desired bioactivity via diffusion bridge. Our method adapts the diffusion bridge to effectively convert pharmacophore arrangements in the spatial space into molecular structures under the manner of SE(3)-equivariant transformation, providing sophisticated control over optimal biochemical feature arrangements on the generated molecules. PharmacoBridge is demonstrated to generate hit candidates that exhibit high binding affinity with potential protein targets.