Publication:
Conformational diversity and protein-protein interfaces in drug repurposing in ras signaling pathway

dc.contributor.departmentDepartment of Computer Engineering
dc.contributor.departmentDepartment of Chemical and Biological Engineering
dc.contributor.departmentGraduate School of Sciences and Engineering
dc.contributor.kuauthorSayın, Ahenk Zeynep
dc.contributor.kuauthorAbalı, Zeynep
dc.contributor.kuauthorŞenyüz, Simge
dc.contributor.kuauthorCankara, Fatma
dc.contributor.kuauthorGürsoy, Attila
dc.contributor.kuauthorKeskin, Özlem
dc.contributor.schoolcollegeinstituteGraduate School of Sciences and Engineering
dc.contributor.schoolcollegeinstituteCollege of Engineering
dc.date.accessioned2024-12-29T09:39:39Z
dc.date.issued2024
dc.description.abstractWe focus on drug repurposing in the Ras signaling pathway, considering structural similarities of protein-protein interfaces. The interfaces formed by physically interacting proteins are found from PDB if available and via PRISM (PRotein Interaction by Structural Matching) otherwise. The structural coverage of these interactions has been increased from 21 to 92% using PRISM. Multiple conformations of each protein are used to include protein dynamics and diversity. Next, we find FDA-approved drugs bound to structurally similar protein-protein interfaces. The results suggest that HIV protease inhibitors tipranavir, indinavir, and saquinavir may bind to EGFR and ERBB3/HER3 interface. Tipranavir and indinavir may also bind to EGFR and ERBB2/HER2 interface. Additionally, a drug used in Alzheimer's disease can bind to RAF1 and BRAF interface. Hence, we propose a methodology to find drugs to be potentially used for cancer using a dataset of structurally similar protein-protein interface clusters rather than pockets in a systematic way.
dc.description.indexedbyWoS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue1
dc.description.openaccessGreen Open Access
dc.description.openaccessGold Open Access
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuTÜBİTAK
dc.description.sponsorsWe would like to thank Prof. Ruth Nussinov, Dr. Hyunbum Jang and Assoc. Prof. Nurcan Tuncbag for their valuable comments. This project has been partially funded by TUSEB 4448/4081 and TUBITAK 2247-120C120.
dc.description.volume14
dc.identifier.doi10.1038/s41598-023-50913-8
dc.identifier.issn2045-2322
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85182187389
dc.identifier.urihttps://doi.org/10.1038/s41598-023-50913-8
dc.identifier.urihttps://hdl.handle.net/20.500.14288/23083
dc.identifier.wos1142684300054
dc.keywordsFactor receptor
dc.keywordsBreast-cancer
dc.keywordsInhibitor nelfinavir
dc.languageen
dc.publisherNature Portfolio
dc.relation.grantnoTUSEB [TUSEB 4448/4081, TUBITAK 2247-120C120]
dc.sourceScientific Reports
dc.subjectBinding protein
dc.subjectProtein
dc.subjectProtein interaction
dc.subjectAmino acids
dc.titleConformational diversity and protein-protein interfaces in drug repurposing in ras signaling pathway
dc.typeJournal article
dspace.entity.typePublication
local.contributor.kuauthorSayın, Ahenk Zeynep
local.contributor.kuauthorAbalı, Zeynep
local.contributor.kuauthorŞenyüz, Simge
local.contributor.kuauthorCankara, Fatma
local.contributor.kuauthorGürsoy, Attila
local.contributor.kuauthorKeskin, Özlem
local.publication.orgunit1Graduate School of Sciences and Engineering
local.publication.orgunit2Department of Computer Engineering;Department of Chemical and Biological Engineering
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