Show simple item record

dc.contributor.authorDrotár, Pavol
dc.contributor.authorJamasb, Arian
dc.contributor.authorDay, Ben
dc.contributor.authorCangea, Cătălina
dc.contributor.authorLio, Pietro
dc.date.accessioned2021-12-21T00:30:11Z
dc.date.available2021-12-21T00:30:11Z
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331624
dc.description.abstractStructure-based drug design involves finding ligand molecules that exhibit structural and chemical complementarity to protein pockets. Deep generative methods have shown promise in proposing novel molecules from scratch (de-novo design), avoiding exhaustive virtual screening of chemical space. Most generative de-novo models fail to incorporate detailed ligand-protein interactions and 3D pocket structures. We propose a novel supervised model that generates molecular graphs jointly with 3D pose in a discretised molecular space. Molecules are built atom-by-atom inside pockets, guided by structural information from crystallographic data. We evaluate our model using a docking benchmark and find that guided generation improves predicted binding affinities by 8% and drug-likeness scores by 10% over the baseline. Furthermore, our model proposes molecules with binding scores exceeding some known ligands, which could be useful in future wet-lab studies.
dc.rightsAll Rights Reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.subjectq-bio.QM
dc.subjectq-bio.QM
dc.subjectcs.LG
dc.titleStructure-aware generation of drug-like molecules
dc.typeArticle
dc.identifier.doi10.17863/CAM.79076
dcterms.dateAccepted2021-10-22
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.contributor.orcidJamasb, Arian [0000-0002-6727-7579]
dc.contributor.orcidLio, Pietro [0000-0002-0540-5053]
rioxxterms.typeJournal Article/Review
pubs.conference-nameMachine Learning in Structural Biology Workshop at the 35th Conference on Neural Information Processing Systems
pubs.conference-start-date2021-12-13
cam.orpheus.counter10*
pubs.conference-finish-date2021-12-13
rioxxterms.freetoread.startdate2022-12-13


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record