Discovery of potential RSK1 inhibitors for cancer therapy using virtual screening, molecular docking, molecular dynamics simulation, and MM/GBSA calculations

Basit Öğe Kaydı
dc.authoridComert Onder, Ferah/0000-0002-4037-1979
dc.contributor.authorKalin, Sevil
dc.contributor.authorOnder, Ferah Comert
dc.date.accessioned2025-01-27T20:55:50Z
dc.date.available2025-01-27T20:55:50Z
dc.date.issued2025
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractThe p90 ribosomal protein S6 Kinase (RSK) family belongs to Ser/Thr protein kinases that includes four isoform RSK1-4 in mammals. The ribosomal protein S6 Kinase 1 (RSK1) is also known as ribosomal protein S6 kinase alpha-1 (RPS6KA1) is a special protein due to their two catalytic regions that is associated with abundantly various cancers and it is proposed as a drug target. Several RSK1 isoform inhibitors have been reported but none of them are used in clinical studies. Thus, we aimed to perform ligand pharmacophore mapping with the known inhibitor and structure-based virtual screening studies to determine potential candidates against RSK1-terminal kinase domains CTKD and NTKD. The studied compounds from the databases (ApexBio, ChEMBL, ChemDiv). The molecular docking study was performed with the resulted candidates by using CDOCKER and Glide/SP methods. The four candidates with the highest docking scores were used for further 100-ns molecular dynamics (MD) simulations and Molecular Mechanics Generalised Born and Surface Area (MM/GBSA) calculations. The root mean square deviation (RMSD) for protein complexes were found between 2 & Aring; and 4 & Aring;. Solvent accessible surface area (SASA), radius of gyration (Rg), and polar surface area (PSA) values were calculated for compounds. The binding free energies were calculated between -72.22 kcal/mol and -82.44 kcal/mol. The interaction diagrams showed that hydrogen bond, alkyl, and pi-alkyl interactions were observed with specific residues such as Leu144, Lys94, Asp142 for RSK1-NTKD, and Cys532, Cys556, Lys447, Asn540 for RSK1-CTKD. The identified compounds may be potential inhibitor candidates of RSK1 following the preclinical studies.
dc.description.sponsorshipScientific and Technological Research Council of TURKIYE (TUBITAK BIDEB)
dc.description.sponsorshipThis study contains a part of the MSc thesis of Sevil Kalin. SK thank the Scientific and Technological Research Council of TURKIYE (TUBITAK BIDEB 2210C scholarship program).
dc.identifier.doi10.1080/07391102.2023.2291830
dc.identifier.endpage1444
dc.identifier.issn0739-1102
dc.identifier.issn1538-0254
dc.identifier.issue3
dc.identifier.pmid38084766
dc.identifier.scopus2-s2.0-85179750532
dc.identifier.scopusqualityQ1
dc.identifier.startpage1424
dc.identifier.urihttps://doi.org/10.1080/07391102.2023.2291830
dc.identifier.urihttps://hdl.handle.net/20.500.12428/26206
dc.identifier.volume43
dc.identifier.wosWOS:001125723500001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherTaylor & Francis Inc
dc.relation.ispartofJournal of Biomolecular Structure & Dynamics
dc.relation.publicationcategoryinfo:eu-repo/semantics/openAccess
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20250125
dc.subjectRSK1
dc.subjectvirtual screening
dc.subjectADMET
dc.subjectpharmacophore
dc.subjectmolecular docking
dc.subjectMD simulation
dc.subjectMM/GBSA
dc.titleDiscovery of potential RSK1 inhibitors for cancer therapy using virtual screening, molecular docking, molecular dynamics simulation, and MM/GBSA calculations
dc.typeArticle

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu