Molecular Docking Studies and Comparative Binding Mode Analysis of FDA Approved HIV Protease Inhibitors

Pran Kishore Deb; Ahmad Junaid; Dina El-Rabie; Tan Yee Hon; Elham Mohammadi Nasr; Mallikarjuna Rao Pichika

doi:10.14233/ajchem.2014.17195

Issue

Vol. 26 No. 18 (2014): Vol 26 Issue 18

Issue Published : September 1, 2014

This work is licensed under a Creative Commons Attribution 4.0 International License.

Molecular Docking Studies and Comparative Binding Mode Analysis of FDA Approved HIV Protease Inhibitors

https://doi.org/10.14233/ajchem.2014.17195

Pran Kishore Deb

Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia

Ahmad Junaid

Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia

Dina El-Rabie

Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia

Tan Yee Hon

Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia

Elham Mohammadi Nasr

Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia

Mallikarjuna Rao Pichika

Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia

Corresponding Author(s) : Pran Kishore Deb

prankishore@imu.edu.my; prankishore1@gmail.com

Asian Journal of Chemistry, Vol. 26 No. 18 (2014): Vol 26 Issue 18
Article Published : September 3, 2014

Abstract

The HIV protease enzyme (maturation enzyme) is one of the most promising therapeutic targets for the treatment of AIDS. Due to the mutation in the virus, there is always room for new agents. In the present study, in silico molecular docking study was carried to analyze and compare the binding mode of nine FDA approved HIV protease inhibitors as well as to understand their structural requirements to inhibit the enzyme by employing the Glide module of Schrodinger software. Prime MM-GBSA approach was used to study the free energy of binding of these inhibitors with the enzyme. QikProp module of Schrodinger was used to predict the ADME properties of study compounds to evaluate their drug likeness. Binding mode analysis shows that the active site is present at the interface of two chains (A and B) of the enzyme and the crucial amino acid residues responsible for the binding of inhibitors to the HIV-1 protease are found to be Asp25, Gly27, Ala28, Asp29 and Gly49, respectively. Also the ADME properties predicted was found to be in ranges predicted by QikProp module of Schrodinger software for 95 % of the known oral drugs. Results of this comparative binding mode analysis of all the FDA approved drugs could be potential and useful for the design of new potent inhibitors of HIV-1 protease.

Keywords

FDA approved HIV protease inhibitors Docking studies in silico ADME prediction

Kishore Deb, P., Junaid, A., El-Rabie, D., Yee Hon, T., Mohammadi Nasr, E., & Rao Pichika, M. (2014). Molecular Docking Studies and Comparative Binding Mode Analysis of FDA Approved HIV Protease Inhibitors. Asian Journal of Chemistry, 26(18), 6227–6232. https://doi.org/10.14233/ajchem.2014.17195

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References

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Maestro version 9.4 and Glide v5.9, Schrödinger, LLC, New York (2013).
D.P. Kishore, M. Raghuprasad, A.R. Rao and P.M. Rao, Asian J. Chem., 25, 10583 (2013); doi:10.14233/ajchem.2013.16184.
P.K. Deb, A. Sharma, P. Piplani and R.R. Akkinepally, Mol. Divers., 16, 803 (2012); doi:10.1007/s11030-012-9394-x.
Prime, version 3.2 Schrodinger, LLC, New York (2013).
QikProp, version 3.6, Schrödinger, LLC, New York (2013).
C.A. Lipinski, F. Lombardo, B.W. Dominy and P.J. Feeney, Adv. Drug Deliv. Rev., 46, 3 (2001); doi:10.1016/S0169-409X(00)00129-0.

References

J. Rebehmed, F. Barbault, C. Teixeira and F. Maurel, J. Comput. Aided Mol. Des., 22, 831 (2008); doi:10.1007/s10822-008-9217-4.

R.A. Weiss, Science, 260, 1273 (1993); doi:10.1126/science.8493571.

Z. Ul-Haq, S. Usmani, H. Shamshad, U. Mahmood and S.A. Halim, Chem. Cent. J., 7, 88 (2013); doi:10.1186/1752-153X-7-88.

Y. Mehellou and E. De Clercq, J. Med. Chem., 53, 521 (2010); doi:10.1021/jm900492g.

N.E. Kohl, E.A. Emini, W.A. Schleif, L.J. Davis, J.C. Heimbach, R.A. Dixon, E.M. Scolnick and I.S. Sigal, Proc. Natl. Acad. Sci. USA, 85, 4686 (1988); doi:10.1073/pnas.85.13.4686.

J.C. Adkins and D. Faulds, Drugs, 55, 837 (1998); doi:10.2165/00003495-199855060-00015.

J.M. Molina and A. Hill, Expert Opin. Harmacother., 8, 1951 (2007); doi:10.1517/14656566.8.12.1951.

G.L. Plosker and S. Noble, Drugs, 58, 1165 (1999); doi:10.2165/00003495-199958060-00011.

P. Tebas and W.G. Powderly, Expert Opin. Pharmacother., 1, 1429 (2000); doi:10.1517/14656566.1.7.1429.

A.P. Lea and D. Faulds, Drugs, 52, 541 (1996); doi:10.2165/00003495-199652040-00007.

J.J. Orrick and C.R. Steinhart, Ann. Pharmacother., 38, 1664 (2004); doi:10.1345/aph.1D394.

Z. Temesgen, F. Cainelli and S. Vento, Drugs Today, 41, 711 (2005); doi:10.1358/dot.2005.41.11.937960.

E.M. Mangum and K.K. Graham, Pharmacotherapy, 21, 1352 (2001); doi:10.1592/phco.21.17.1352.34419.

K. Bragman, Adv. Exp. Med. Biol., 394, 305 (1996); doi:10.1007/978-1-4757-9209-6_28.

S. Becker and L. Thornton, Expert Opin. Pharmacother., 5, 1995 (2004); doi:10.1517/14656566.5.9.1995.

Maestro version 9.4 and Glide v5.9, Schrödinger, LLC, New York (2013).

D.P. Kishore, M. Raghuprasad, A.R. Rao and P.M. Rao, Asian J. Chem., 25, 10583 (2013); doi:10.14233/ajchem.2013.16184.

P.K. Deb, A. Sharma, P. Piplani and R.R. Akkinepally, Mol. Divers., 16, 803 (2012); doi:10.1007/s11030-012-9394-x.

Prime, version 3.2 Schrodinger, LLC, New York (2013).

QikProp, version 3.6, Schrödinger, LLC, New York (2013).

C.A. Lipinski, F. Lombardo, B.W. Dominy and P.J. Feeney, Adv. Drug Deliv. Rev., 46, 3 (2001); doi:10.1016/S0169-409X(00)00129-0.

Issue

Vol. 26 No. 18 (2014): Vol 26 Issue 18

Molecular Docking Studies and Comparative Binding Mode Analysis of FDA Approved HIV Protease Inhibitors

Corresponding Author(s) : Pran Kishore Deb

Abstract

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