The size matters? A computational tool to design bivalent ligands.

ABSTRACT:

Motivation

Bivalent ligands are increasingly important such as for targeting G protein-coupled receptor (GPCR) dimers or proteolysis targeting chimeras (PROTACs). They contain two pharmacophoric units that simultaneously bind in their corresponding binding sites, connected with a spacer chain. Here, we report a molecular modelling tool that links the pharmacophore units via the shortest pathway along the receptors van der Waals surface and then scores the solutions providing prioritization for the design of new bivalent ligands.

Results

Bivalent ligands of known dimers of GPCRs, PROTACs and a model bivalent antibody/antigen system were analysed. The tool could rapidly assess the preferred linker length for the different systems and recapitulated the best reported results. In

SUBMITTER: Perez-Benito L 

PROVIDER: S-EPMC6223368 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature