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dc.contributor.authorHeid, Esther
dc.contributor.authorGoldman, Samuel
dc.contributor.authorSankaranarayanan, Karthik
dc.contributor.authorColey, Connor Wilson
dc.contributor.authorFlamm, Christoph
dc.contributor.authorGreen Jr, William H
dc.date.accessioned2021-10-26T15:38:43Z
dc.date.available2021-10-26T15:38:43Z
dc.date.issued2021-09
dc.date.submitted2021-07
dc.identifier.issn1549-9596
dc.identifier.issn1549-960X
dc.identifier.urihttps://hdl.handle.net/1721.1/133128
dc.description.abstractData-driven computer-aided synthesis planning utilizing organic or biocatalyzed reactions from large databases has gained increasing interest in the last decade, sparking the development of numerous tools to extract, apply, and score general reaction templates. The generation of reaction rules for enzymatic reactions is especially challenging since substrate promiscuity varies between enzymes, causing the optimal levels of rule specificity and optimal number of included atoms to differ between enzymes. This complicates an automated extraction from databases and has promoted the creation of manually curated reaction rule sets. Here, we present EHreact, a purely data-driven open-source software tool, to extract and score reaction rules from sets of reactions known to be catalyzed by an enzyme at appropriate levels of specificity without expert knowledge. EHreact extracts and groups reaction rules into tree-like structures, Hasse diagrams, based on common substructures in the imaginary transition structures. Each diagram can be utilized to output a single or a set of reaction rules, as well as calculate the probability of a new substrate to be processed by the given enzyme by inferring information about the reactive site of the enzyme from the known reactions and their grouping in the template tree. EHreact heuristically predicts the activity of a given enzyme on a new substrate, outperforming current approaches in accuracy and functionality.en_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1021/acs.jcim.1c00921en_US
dc.rightsCreative Commons Attribution 4.0 International licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.sourceACSen_US
dc.titleEHreact: Extended Hasse Diagrams for the Extraction and Scoring of Enzymatic Reaction Templatesen_US
dc.typeArticleen_US
dc.identifier.citationHeid, Esther et al. "EHreact: Extended Hasse Diagrams for the Extraction and Scoring of Enzymatic Reaction Templates." Journal of Chemical Information and Modeling 61, 10 (September 2021): 4949–4961. © 2021 The Authorsen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Computational and Systems Biology Programen_US
dc.relation.journalJournal of Chemical Information and Modelingen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.date.submission2021-10-25T18:16:21Z
mit.journal.volume61en_US
mit.journal.issue10en_US
mit.licensePUBLISHER_CC
mit.metadata.statusCompleteen_US


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