Deep scaffold hopping with multimodal transformer neural networks.

ABSTRACT: Scaffold hopping is a central task of modern medicinal chemistry for rational drug design, which aims to design molecules of novel scaffolds sharing similar target biological activities toward known hit molecules. Traditionally, scaffolding hopping depends on searching databases of available compounds that can't exploit vast chemical space. In this study, we have re-formulated this task as a supervised molecule-to-molecule translation to generate hopped molecules novel in 2D structure but similar in 3D structure, as inspired by the fact that candidate compounds bind with their targets through 3D conformations. To efficiently train the model, we curated over 50 thousand pairs of molecules with increased bioactivity, similar 3D structure, but different 2D structure from public bioactivity da

SUBMITTER: Zheng S 

PROVIDER: S-EPMC8590293 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature