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Molecular docking, QPLD, and ADME prediction studies on HIV-1 integrase leads

Medicinal Chemistry Research volume 21, pages 4239–4251 (2012)Cite this article

Abstract

HIV-1 integrase (IN) is an important drug target over the years with diverse therapeutic potential with the objective of designing new chemical entities with enhanced inhibitory potencies against HIV-1 IN. We performed molecular docking, quantum polarized ligand docking (QPLD), ADME screening, and PASS biological activity prediction studies on Raltegravir, Elvitegravir, and newly searched compounds of Cambridge crystallographic database. Best docking and QPLD scores of known and unknown searched compounds were compared using docking score, docking energy, and emodel energy. Moreover, correlation between docking score, docking energy with emodel energy yielded a statistically significant correlation coefficient. The searched compounds were also evaluated with ADME properties and biological activity prediction analysis. These compounds also show good pharmacokinetic properties under the acceptable range including antiviral biological activity prediction. Hence, these compounds could be employed to design ligands with enhanced inhibitory potencies and to predict the potencies of analogs to guide synthesis/or prepare synthetic analogs for second generation drug development against HIV-1 IN.

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Acknowledgments

The authors like to thank Department of Bioinformatics, Alagappa University, Karaikudi, for the support and facility provided for this study. The authors thank to anonymous referee for the valuable suggestion.

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Authors and Affiliations

  1. Computer-Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, 630002, India

    Sunil Kumar Tripathi, Chandrabose Selvaraj, Sanjeev Kumar Singh & Karnati Konda Reddy

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  1. Sunil Kumar Tripathi
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  2. Chandrabose Selvaraj
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  3. Sanjeev Kumar Singh
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Correspondence to Sanjeev Kumar Singh.

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Tripathi, S.K., Selvaraj, C., Singh, S.K. et al. Molecular docking, QPLD, and ADME prediction studies on HIV-1 integrase leads. Med Chem Res 21, 4239–4251 (2012). https://doi.org/10.1007/s00044-011-9940-6

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  • DOI: https://doi.org/10.1007/s00044-011-9940-6

Keywords

  • HIV-1 integrase
  • Docking
  • ADME
  • QM/MM
  • QPLD
  • CSD