Assessment of interaction of human OCT 1-3 proteins and metformin using silico analyses
Acta Chimica Slovenica, cilt.67, sa.4, ss.1202-1215, 2020 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 67 Sayı: 4
- Basım Tarihi: 2020
- Doi Numarası: 10.17344/acsi.2020.6108
- Dergi Adı: Acta Chimica Slovenica
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Central & Eastern European Academic Source (CEEAS), Chemical Abstracts Core, EMBASE, MEDLINE, Directory of Open Access Journals, DIALNET
- Sayfa Sayıları: ss.1202-1215
- Anahtar Kelimeler: Organic cation transporters, metformin, protein structure prediction, model Validation, docking
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Metformin, a drug frequently used by diabetic patients as the first-line treatment worldwide, is positively charged and is transported into the cell through human organic cation transporter (hOCT 1-3) proteins. We aimed to mimic the cellular uptake of metformin by hOCT1-3 with various bioinformatics methods and tools. 3D structure of OCT1-3 proteins was predicted by considering the structures and function of these proteins. We predicted functional regions (active and ligand binding sites) of OCT1-3 and performed comparative bioinformatics analysis. The predicted structure of hOCT1-3 was then analyzed in the Blind Docking server and the results were confirmed with predicted binding site residues and conserved domain regions. We simulated the OCT1-3 and metformin docking and also validated the docking procedure with other substrates of HOCT1-3 proteins. We selected the best poses of metformin docking simulations as per binding energy (–5.27 to –4.60 kcal/mol). Lastly, we validated the static description of protein-ligand (OCT-Metformin) interactions by performing molecular dynamics simulation. Eventually, we obtained stable simulation of OCT-metformin interaction.