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Dergiler / Journal of the Turkish Chemical Society Section A: Chemistry / 2017 / Cilt: 4 - Sayı: 1

Docking and Molecular Dynamics Calculations of Some Previously Studied and newly Designed Ligands to Catalytic Core Domain of HIV-1 Integrase and an Investigation to Effects of Conformational Changes of Protein on Docking Results

Selami Ercan
Sayfa
243–270
Yayın Tarihi
2017-01-09
DOI
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

The questions about the ligands which have low docking scores in a conformation of protein could give better scores in another conformation of protein and if the MD simulations carry the different oriented and different localized ligands in same position at the end of simulation were answered.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:Nowadays, AIDS still remains as a worldwide pandemic and continues to cause many death which arise from HIV-1 virus.
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Temel Bulgular & Veri:For nearly 35 years, drugs that target various steps of virus life cycle have been developed.
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Sonuç & Katkı:The questions about the ligands which have low docking scores in a conformation of protein could give better scores in another conformation of protein and if the MD simulations carry the different oriented and different localized ligands in same position at the end of simulation were answered.
🔬Tür:Araştırma Makalesi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:HIV-1 integrase · drug design · docking

Abstract

Nowadays, AIDS still remains as a worldwide pandemic and continues to cause many death which arise from HIV-1 virus. For nearly 35 years, drugs that target various steps of virus life cycle have been developed. HIV-1 integrase is the one of these steps which is essential for virus life cycle. Computer aided drug design is being used in many drug design studies as also used in development of the first HIV-1 integrase inhibitor Raltegravir. In this study 3 ligands which are used as HIV-1 integrase inhibitors and 4 newly designed ligands were docked to catalytic core domain of HIV-1 integrase. Each of ligands docked to three different conformations of protein. Prepared complexes (21 item) were carried out by 50 ns MD simulations and results were analyzed. Finally, the binding free energies of ligands were calculated. Hereunder, it was determined that designed ligands L01 and L03 gave favorable results. The questions about the ligands which have low docking scores in a conformation of protein could give better scores in another conformation of protein and if the MD simulations carry the different oriented and different localized ligands in same position at the end of simulation were answered.

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Bu Makaleye Atıf Yap

Ercan, S. (2017). Docking and Molecular Dynamics Calculations of Some Previously Studied and newly Designed Ligands to Catalytic Core Domain of HIV-1 Integrase and an Investigation to Effects of Conformational Changes of Protein on Docking Results. Journal of the Turkish Chemical Society Section A: Chemistry, Cilt: 4 - Sayı: 1, 243–270. https://ajindex.com/articles/781588

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Kaynakça (13)

  1. Global Aids Response Progress Reporting 2015. 2015.
  2. Miri L, Bouvier G, Kettani A, Mikou A, Wakrim L, Nilges M, et al. Stabilization of the integrase-DNA complex by Mg2+ ions and prediction of key residues for binding HIV-1 integrase inhibitors. Proteins. 2014;82(3):466-78.
  3. Pendri A, Meanwell NA, Peese KM, Walker MA. New first and second generation inhibitors of human immunodeficiency virus-1 integrase. Expert Opin Ther Patents. 2011;21(8):1173-89.
  4. Zhang D, Debnath B, Yu S, Sanchez TW, Christ F, Liu Y, et al. Design and discovery of 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide inhibitors of HIV-1 integrase. Bioorganic & medicinal chemistry. 2014;22(19):5446-53.
  5. Mehellou Y, De Clercq E. Twenty-six years of anti-HIV drug discovery: where do we stand and where do we go? J Med Chem. 2010;53(2):521-38.
  6. De Luca L, De Grazia S, Ferro S, Gitto R, Christ F, Debyser Z, et al. HIV-1 integrase strand-transfer inhibitors: design, synthesis and molecular modeling investigation. Eur J Med Chem. 2011;46(2):756-64.
  7. DeGruttola V, Dix L, D'Aquila R, Holder D, Phillips A, Ait-Khaled M, et al. The relation between baseline HIV drug resistance and response to antiretroviral therapy: re-analysis of retrospective and prospective studies using a standardized data analysis plan. Antiviral therapy. 2000;5(1):41-8.
  8. Goethals O, Van Ginderen M, Vos A, Cummings MD, Van Der Borght K, Van Wesenbeeck L, et al. Resistance to raltegravir highlights integrase mutations at codon 148 in conferring cross-resistance to a second-generation HIV-1 integrase inhibitor. Antiviral Res. 2011;91(2):167-76. Richman DD. Antiviral drug resistance. Antiviral Res. 2006;71(2-3):117-21.
  9. Calmy A, Hirschel B, Cooper DA, Carr A. A new era of antiretroviral drug toxicity. Antiviral therapy. 2009;14(2):165-79.
  10. Clavel F, Hance AJ. HIV drug resistance. N Engl J Med. 2004;350(10):1023-35.
  11. Emini EA, Graham DJ, Gotlib L, Condra JH, Byrnes VW, Schleif WA. HIV and multidrug resistance. Nature. 1993;364(6439):679. Geeraert L, Kraus G, Pomerantz RJ. Hide-and-seek: the challenge of viral persistence in HIV-1 infection. Annu Rev Med. 2008;59:487-501.
  12. Johnson VA, Brun-Vezinet F, Clotet B, Gunthard HF, Kuritzkes DR, Pillay D, et al. Update of the drug resistance mutations in HIV-1: December 2010. Top HIV Med. 2010;18(5):156-63.
  13. Malta M, Magnanini MM, Strathdee SA, Bastos FI. Adherence to antiretroviral therapy among HIV-infected drug users: a meta-analysis. AIDS Behav. 2010;14(4):731-47. Marcello A. Latency: the hidden HIV