Note: COSMIC-3D provides structural perspectives on cancer genetics for drug discovery

Note: COSMIC-3D provides structural perspectives on cancer genetics for drug discovery

(doi: 10.1038/s41588-018-0214-9)

• COSMIC-3D is designed to enable greater understanding of the functional impact of mutations, generate new hypotheses on which mutations are cancer drivers and provide new opportunities for addressing these mutations pharmaceutically.

• genetics, structural proteomics and drug development can be best described as ‘mutation-guided drug design’.

• there remains much scope for expansion of the repertoire of precision therapeutic drugs targeting these mutations.

• Both cancer genomic and protein structural data sources are individually great assets for scientists working in the field of oncology drug discovery.

• COSMIC-3D currently maps cancer variant data for nearly 9,300 genes to nearly 37,000 protein structures, covering 390 key genes from the Cancer Gene Census.

• The structure viewer displays the protein structure and small-molecule ligands, as well as protein–protein or protein–DNA interfaces where available, allowing mutations to be interpreted in the context of these functional binding sites.

• druggability’ scores, derived from fPocket.

• Challenges remain in predicting these effects from the wild-type structure, and hypotheses generated should be carefully explored.

• COSMIC-3D shows the location of recurrent missense mutations on protein structures as 3D ‘heat maps’ indicating mutation frequency, immediately illustrating the structural and functional contexts of these mutations. This is intended to highlight key cancer driver mutations.

• The COSMIC-3D ‘human structural proteome of oncology’ aims to empower the drug discovery process with cancer genomics.