PhoreGen is a pharmacophore-oriented 3D molecular generation framework designed to generate entire 3D molecules that are precisely aligned with a given pharmacophore model. It employs asynchronous perturbations and simultaneously updates on both atomic and bond information, coupled with a message-passing mechanism that incoporates prior knowledge of ligand-pharmacophore mapping during the diffusion-denoising process. By hierarchical learning on a large number of ligand-pharmacophore pairs derived from 3D ligands, complex structures, and docking-produced potential binding modes, PhoreGen can generate chemically and energetically reasonable 3D molecules well-aligned with the pharmacophore constraints, while maintaining structural diversity, drug-likeness, and potentially high binding affinity. Notably, it excels in generating feature-customized molecules, e.g. with covalent groups and metal-binding motifs, at high frequency, demonstrating its unparalleled ability and practicality even for challenging drug design scenarios.
📑 Here shows the process of PhoreGen generating an entire 3D molecule under the pharmacophore constraint.
generation_demo.mp4
MBL_SBL_demo.mp4
We here provide a user-friendly web server for this purpose.
Please visit https://ancphore.ddtmlab.org/Modeling
For questions or feedback, please contact:
- Peng Jian: [email protected]
- Li Guo-Bo: [email protected]
- Visit our Lab Website for more details about PhoreGen and related projects.