COMPUTATIONAL EVALUATION OF GINSENOSIDES AS ALTERNATIVE THERAPEUTIC AGENTS TARGETING THE BREAST CANCER-ASSOCIATED BARD1 GENE: MOLECULAR DOCKING AND ARTIFICIAL INTELLIGENCE APPROACHES

Yıl 2025, Cilt: 1 Sayı: 2, 36 - 44, 29.09.2025

Nil Sazlı , Deniz Karataş

Öz

Breast cancer associated with the BARD1 gene occurs when the cell cycle in breast tissue becomes abnormal and proliferates uncontrollably. The increasing incidence of breast cancer, particularly in recent years, has become a significant public health concern. This study investigates the potential of ginsenosides derived from the Panax ginseng plant, known for their anticancer bioactive properties, as alternative drug candidates to chemical synthetic agents in breast cancer treatment. Within the scope of the study, the crystal structure of the BARD1 gene (PDB ID: 3C5R) receptor, along with Ginsenoside Rk1, Ginsenoside Ro, Pseudoginsenoside Rt5, and Vinaginsenoside R3 ginsenosides, as well as the reference drugs 5-Fluorouracil (5FU), Carboplatin, Docetaxel, and Ixabeliplane, were subjected to molecular docking to evaluate their potential anticancer bioactive activities and binding affinities to the BARD1 receptor. An artificial intelligence-based model was developed to optimize the binding energy between the receptor and the ligands in question, and the docking process was repeated to select the best receptor-ligand complex. The most promising potential drug candidate among the receptor-ligand complexes was identified, and its pharmacokinetic properties were evaluated using ADMET analyses. According to the findings, while Docetaxel (-9.5 kcal/mol) exhibited the highest binding affinity among chemical agents, natural ginsenosides such as Ginsenoside Ro (-9.5 kcal/mol) and Ginsenoside Rk1 (-9.0 kcal/mol) demonstrated binding affinities comparable to the reference ligands. Based on artificial intelligence-based molecular docking binding energy predictions, the receptor-ligand complexes formed with Ginsenoside Ro (-8.54 kcal/mol) and Carboplatin (-9.82 kcal/mol) achieved the best scores. The results of this study indicate that Panax ginseng-derived ginsenosides exhibit binding energies similar to those of chemical compounds against the BARD1 gene receptor associated with breast cancer. These findings are highly promising for preclinical studies, supporting the potential evaluation of ginsenosides as natural alternatives in breast cancer treatment.

Anahtar Kelimeler

Breast cancer , Molecular docking , artificial intelligence , H-bond , interaction energy , ADMET

MEME KANSERİ İLE İLİŞKİLİ BARD1 GENİ İÇİN ALTERNATİF TERAPÖTİK AJANLAR OLARAK GİNSENOSİDLERİN HESAPLAMALI DEĞERLENDİRİLMESİ: MOLEKÜLER DOCKİNG VE YAPAY ZEKA YAKLAŞIMLARI

Öz

BARD1 geni ile ilişkilendirilen meme kanseri, meme dokusunda bulunan hücre döngüsünün anormalleşerek kontrolsüz çoğalması ile meydana gelmektedir. Özellikle son yıllarda meme kanseri vakalarının artması ciddi bir sağlık sorunu haline gelmiştir. Çalışma da Panax ginseng bitkisinden elde edilen antikanser biyoaktif özelliğine sahip ginsenosid türevlerinin meme kanseri tedavisinde kimyasal sentetik ajanlara alternatif bir ilaç adayı olma potansiyeli incelenmiştir. Çalışma kapsamında BARD1 genine ait kristal yapı (PDB ID: 3C5R) reseptörü ile Ginsenoside Rk1, Ginsenoside Ro, Pseudoginsenoside Rt5, Vinaginsenoside R3 ginsenosidleri ve referans ilaç olarak seçilen 5-Fluorouracil (5FU), Carboplatin, Docetaxel ve Ixabeliplane bileşiklerin potansiyel antikanser biyoaktif ajan olarak etkinliklerini ve BARD1 reseptörüne karşı bağlanma güçlerini belirlemek adına moleküler docking işlemine tabi tutulmuştur. Söz konusu reseptör ve ligandların arasındaki bağlanma enerjisinin optimizasyonu adına yapay zeka tabanlı bir model geliştirilerek docking işlemi tekrarlanarak en iyi reseptör-ligand kompleksi seçilmiştir. Reseptör-ligand komplekslerine ait en iyi potansiyel ilaç adayını belirlemek ve farmakokinetik özellikleri ADMET analizleri ile değerlendirilmiştir. Elde edilen bulgulara göre kimyasal ajanlardan en iyi sonucu Docetaxel (-9.5 kcal/mol) verirken Ginsenoside Ro (-9.5 kcal/mol), Ginsenoside Rk1 (-9.0 kcal/mol) gibi doğal ginsenosidler referans ligandlar ile oldukça yakın sonuçlat göstermiştir. Yapay zeka tabanlı moleküler docking bağlanma enerjilerine göre ise Ginsenoside Ro (-8.54 kcal/mol) ve Carboplatin (-9.82 kcal/mol) ile oluşturulan reseptör-ligand kompleksi en iyi skoru vermiştir. Çalışmamızın sonuçlarına göre belirlenen Panax ginseng türevi ginsenosidler meme kanseri ile ilişkili BARD1 genine ait reseptöre karşı kimyasal bileşenlere benzer bir şekilde olddukça iyi bir bağlanma enerjisi göstermiştir. Bu bulguşar ginsenosidlerin meme kanserine yönelik tedavide doğal bir alternatif olarak değerlenririlerek preklinik çalışmalar için oldukça umut vericidir.

Anahtar Kelimeler

Meme Kanseri , Moleküler Kenetlenme , Yapay Zeka , Hidrojen Bağı , Etkileşim Enerjisi , ADMET

Kaynakça

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