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master's thesis
Razvoj potencijalnih inhibitora humanog BRD2 proteina
2024. urn:nbn:hr:171:247555
Kranjčević, Elena
University of Split
School of Medicine

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Kranjčević, E. (2024). Razvoj potencijalnih inhibitora humanog BRD2 proteina (Master's thesis). Split: University of Split, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:171:247555

Kranjčević, Elena. "Razvoj potencijalnih inhibitora humanog BRD2 proteina." Master's thesis, University of Split, School of Medicine, 2024. https://urn.nsk.hr/urn:nbn:hr:171:247555

Kranjčević, Elena. "Razvoj potencijalnih inhibitora humanog BRD2 proteina." Master's thesis, University of Split, School of Medicine, 2024. https://urn.nsk.hr/urn:nbn:hr:171:247555

Kranjčević, E. (2024). 'Razvoj potencijalnih inhibitora humanog BRD2 proteina', Master's thesis, University of Split, School of Medicine, accessed 22 November 2024, https://urn.nsk.hr/urn:nbn:hr:171:247555

Kranjčević E. Razvoj potencijalnih inhibitora humanog BRD2 proteina [Master's thesis]. Split: University of Split, School of Medicine; 2024 [cited 2024 November 22] Available at: https://urn.nsk.hr/urn:nbn:hr:171:247555

E. Kranjčević, "Razvoj potencijalnih inhibitora humanog BRD2 proteina", Master's thesis, University of Split, School of Medicine, Split, 2024. Available at: https://urn.nsk.hr/urn:nbn:hr:171:247555

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Metadata
TitleRazvoj potencijalnih inhibitora humanog BRD2 proteina
Title (english)Development of potential inhibitors of the human BRD2 protein
AuthorElena Kranjčević
MentorDario Leskur (mentor)
Committee memberAna Šešelja Perišin (predsjednik povjerenstva)
Committee memberAngela Mastelić (član povjerenstva)
Committee memberDario Leskur (član povjerenstva)
GranterUniversity of Split
School of Medicine
Split
Defense date and country2024-10-24, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Pharmacy
Pharmacy
Abstract
Cilj istraživanja: Otkriti nove potencijalne inhibitore humanog BRD2 proteina kako bi se koristili u terapiji liječenja tumora koji su povezani s aktivnošću ovoga proteina. Metode: U PDB-u, za analizu je odabrana struktura BRD4 u kompleksu s LANA proteinom, pri čemu je LANA protein služio kao spoj uzor. Farmakofori su identificirani u softveru Discovery Studio 2024, dok je probir molekula proveden putem mrežnog servisa ZINCPharmer. Obrada receptora izvršena je u programu Chimera, a liganda u programima Open Babel i Meeko. Molekularno sidrenje provedeno je pomoću programa AutoDock Vina na superračunalu. Sidrenje je validirano mjerenjem RMSD vrijednosti između rezultata dobivenih u programima AutoDock Vina i AutoDock4. Vizualizacija kompleksa ligand-receptor napravljena je u ChimeraX, a analiza vezanja u Discovery Studio 2024. Srčana toksičnost predviđena je korištenjem računalnog alata PRED-hERG 5.0, dok su fizikalno-kemijska svojstva liganda izračunata pomoću RDKit-a. Ligandi su rangirani prema rezultatima sidrenja, fizikalno-kemijskim svojstvima i predviđenoj kardiotoksičnosti. Rezultati: Prema farmakofornoj mapi izrađenoj na temelju vezivanja LANA proteina za ET domenu BRD4 proteina identificirano je 82 molekule potencijalnih inhibitora. Određen je afinitet vezanja za receptor, fizikalno-kemijske osobine i procijenjena kardiotoksičnost. Na temelju najpovoljnijeg afiniteta i isključenoj kardiotoksičnosti izabrano je 10 najboljih liganda koji su izdvojeni za daljnje analize. Zaključak: Identificirane su molekule potencijalnih inhibitora ET domene humanog BRD2 proteina. Ove molekule potrebno je optimizirati, sintetizirati te dobivene rezultate eksperimentalno potvrditi kako bi se potencijalno nastavio razvoj ovih lijekova i time unaprijedili terapijski postupci u liječenju raka.
Abstract (english)
Objectives: To discover new potential inhibitors of the human BRD2 protein for use in tumor therapy associated with the activity of this protein. Methods: In the PDB, the structure of BRD4 in complex with the LANA protein was selected for analysis, with LANA protein serving as a reference compound. Pharmacophores were identified using Discovery Studio 2024 software, while molecule screening was conducted through the ZINCPharmer web service. The receptor was processed in Chimera, and the ligands in Open Babel and Meeko. Molecular docking was performed using AutoDock Vina on a supercomputer. Docking was validated by measuring the RMSD values between results obtained from AutoDock Vina and AutoDock4. The ligand-receptor complex was visualized in ChimeraX, and binding analysis was conducted in Discovery Studio 2024. Cardiotoxicity was predicted using the PRED-hERG 5.0 computational tool, and the ligand’s physicochemical properties were calculated using RDKit. Ligands were ranked based on docking results, physicochemical properties, and predicted cardiotoxicity. Results: Based on the pharmacophore map created from the binding of the LANA protein to the ET domain of the BRD4 protein, 82 potential inhibitors were identified. The binding affinity for the receptor, physicochemical properties, and potential cardiotoxicity were determined. Ten top ligands were chosen for further research based on their optimal affinity and absence of cardiotoxicity. Conclusion: The molecules of potential inhibitors of the human BRD2 protein have been identified. These molecules need to be optimized, synthesized, and experimentally validated in order to potentially advance the development of these drugs and improve therapeutic approaches in cancer treatment.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:171:247555
Study programmeTitle: Pharmacy
Study programme type: university
Study level: integrated undergraduate and graduate
Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Embargo expiration date: 2024-10-24
Terms of useLicence In copyright icon
Created on2024-10-23 11:40:21