Identifying the Novel Pyrimidine-Based CDK2 Inhibitors as Anticancer Agents Using Text-Mining and Combined Molecular Modeling Approaches

Kader SAHİN; Serdar DURDAGI

doi:https://doi.org/10.18596/jotcsa.701243

Makale detayları

Identifying the Novel Pyrimidine-Based CDK2 Inhibitors as Anticancer Agents Using Text-Mining and Combined Molecular Modeling Approaches

Yazarlar:

Kader SAHİN | Serdar DURDAGI

Yayıncı:

Turkish Chemical Society

Ana Başlıklar:

İnsan psikolojisi

Dergi:

Journal of the Turkish Chemical Society Section A: Chemistry 2020 Vol.7 Issue 2, pp.383-404

Belge Tipi:

Makale

Yayın Tarihi:

6/2020

Belge Dili:

İngilizce

Document ID (Org No.):

2000502587

Sıklık:

Üç Aylık

eISSN:

2149-0120

DOI:

https://doi.org/10.18596/jotcsa.701243

Özet:

 

The cycline-dependent kinase (CDK) protein is an important target used in anti-cancer drug designing studies. Pyrimidine is a crucial fragment which is used in many FDA-approved drugs including anti-cancer drugs. In the current study, a small molecule database (Specs SC) that includes more than 210.000 compounds were used in text mining studies and 6668 molecules that carry “pyrimidine” fragments were filtered. These compounds were then screened at the binding pocket of CDK-2 target using molecular docking and molecular dynamics (MD) simulations approaches. Binding free energies of screened compounds were also compared with pyrimidine-based FDA approved anti-cancer drug Abemaciclib which targets CDK. Based on comparison of docking scores of screened compounds, top-7 hits were used in 100 ns MD simulations. Same MD simulations protocol (100 ns) were also applied to Abemaciclib-bound CDK-2 complex structure. Average Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) energies were then calculated. Our MM/GBSA results showed that 6 out of 7 compounds have better MM/GBSA scores than FDA approved compound Abemaciclib. Thus, together with combination of text mining and integrated molecular modeling approaches, we identified novel pyrimidine-based hits against CDK.

Makale detayları

Identifying the Novel Pyrimidine-Based CDK2 Inhibitors as Anticancer Agents Using Text-Mining and Combined Molecular Modeling Approaches

Yazarlar: Kader SAHİN | Serdar DURDAGI

Yayıncı: Turkish Chemical Society

Ana Başlıklar: İnsan psikolojisi

Dergi: Journal of the Turkish Chemical Society Section A: Chemistry 2020 Vol.7 Issue 2, pp.383-404

Belge Tipi: Makale

Yayın Tarihi: 6/2020

Belge Dili: İngilizce

Document ID (Org No.): 2000502587

Sıklık: Üç Aylık

eISSN: 2149-0120

DOI: https://doi.org/10.18596/jotcsa.701243

Sayı

Yazarlar:

Kader SAHİN | Serdar DURDAGI

Yayıncı:

Turkish Chemical Society

Ana Başlıklar:

İnsan psikolojisi

Dergi:

Journal of the Turkish Chemical Society Section A: Chemistry 2020 Vol.7 Issue 2, pp.383-404

Belge Tipi:

Makale

Yayın Tarihi:

6/2020

Belge Dili:

İngilizce

Document ID (Org No.):

2000502587

Sıklık:

Üç Aylık

eISSN:

2149-0120

DOI:

https://doi.org/10.18596/jotcsa.701243