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dc.contributor.authorBelkin, Saveliy
dc.contributor.authorKundrotas, Petras J.
dc.contributor.authorVakser, Ilya A.
dc.identifier.citationBelkin, S., Kundrotas, P. J., & Vakser, I. A. (2018). Inhibition of protein interactions: co-crystalized protein-protein interfaces are nearly as good as holo proteins in rigid-body ligand docking. Journal of computer-aided molecular design, 32(7), 769–779. doi:10.1007/s10822-018-0124-zen_US
dc.description.abstractModulating protein interaction pathways may lead to the cure of many diseases. Known protein–protein inhibitors bind to large pockets on the protein–protein interface. Such large pockets are detected also in the protein–protein complexes without known inhibitors, making such complexes potentially druggable. The inhibitor-binding site is primary defined by the side chains that form the largest pocket in the protein-bound conformation. Low-resolution ligand docking shows that the success rate for the protein-bound conformation is close to the one for the ligand-bound conformation, and significantly higher than for the apo conformation. The conformational change on the protein interface upon binding to the other protein results in a pocket employed by the ligand when it binds to that interface. This proof-of-concept study suggests that rather than using computational pocket-opening procedures, one can opt for an experimentally determined structure of the target co-crystallized protein–protein complex as a starting point for drug design.en_US
dc.publisherSpringer International Publishingen_US
dc.rights© Springer International Publishing AG, part of Springer Nature 2018en_US
dc.subjectMolecular recognitionen_US
dc.subjectDrug designen_US
dc.subjectConformational propertiesen_US
dc.subjectMolecular modelingen_US
dc.subjectLigand–receptor interactionen_US
dc.titleInhibition of protein interactions: co-crystalized protein–protein interfaces are nearly as good as holo proteins in rigid-body ligand dockingen_US
kusw.kuauthorBelkin, Saveliy
kusw.kuauthorKundrotas, Petras J.
kusw.kuauthorVakser, Ilya A.
kusw.kudepartmentComputational Biologyen_US
kusw.kudepartmentMolecular Biosciencesen_US
kusw.oanotesPer SHERPA/RoMEO Author's Pre-print: green tick author can archive pre-print (ie pre-refereeing) Author's Post-print: green tick author can archive post-print (ie final draft post-refereeing) Publisher's Version/PDF: cross author cannot archive publisher's version/PDF General Conditions:

Author's pre-print on author's personal website, non-commercial pre-print server Author's post-print on author's personal website immediately Author's post-print on institutional repository or funder designated repository after 12 months embargo from first online publication Publisher's version/PDF cannot be used Published source must be acknowledged Must link to publisher version with DOI Post-prints are subject to Springer Nature re-use terms
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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