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Systematic investigation on the binding of GW420867X as HIV-1 reverse transcriptase inhibitor

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Abstract

The interactions between ligands and the surrounding binding site depend on the different contributions of individual amino acids. The determination of these particular interaction energies is sensitive to the model used, i.e., which part of the amino acids is taken into account and which terminating procedure is applied. In this study, the subtle interaction between individual residues from the HIV-1 reverse transcriptase allosteric binding site and an inhibitor, isopropyl (S)-2-ethyl-7-fluoro-3,4-dihydro-3-oxoquinoxalin-1(2H)-carboxylate (GW420867X), was investigated by using high-level quantum chemical calculations (MP2, M06-2X, and B3LYP) with the following basis sets: 6-31G(d), 6-31G(d,p), 6-311G(d), and 6-311G(d,p). The results obtained indicate that the interaction between the inhibitor and Lys101 is the most important one for the binding. We have calculated this interaction using various models to evaluate the effect of neighboring residues. Electrostatic interactions induced by the terminating substituents were also studied using natural population analysis. The results show that even systems where the amide bond is cut and capped with hydrogen atoms can be used as reliable models for estimating the individual interaction energies. Furthermore, the interaction energies of GW420867X in wild-type and Lys101Glu mutant are also investigated to explain the loss of GW420867X’s activity in the Lys101Glu mutant.

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References

  1. Jacobo-Molina A, Arnold E (1991) Biochemistry 30:6351

    Article  CAS  Google Scholar 

  2. Jacobo-Molina A, Ding J, Nanni RG, Clark AD Jr, Lu X, Tantillo C, Williams RL, Kamer G, Ferris AL, Clark P, Hizi A, Hughesi SH, Arnold E (1993) Proc Natl Acad Sci USA 90:6320

    Article  CAS  Google Scholar 

  3. Balzarini J (1999) Biochem Pharmacol 58:1

    Article  CAS  Google Scholar 

  4. Ren J, Stammers DK (2005) Trends Pharmacol Sci 26:4

    Article  CAS  Google Scholar 

  5. De Clercq E (1998) Antiviral Res 38:153

    Article  Google Scholar 

  6. Menéndez-Arias L (2002) Trends Pharmacol Sci 23:381

    Article  Google Scholar 

  7. De Clercq E (2009) Int J Antimicrob Agents 33:307

    Article  Google Scholar 

  8. Ren J, Nichols CE, Chamberlain PP, Weaver KL, Short SA, Chan JH, Kleim JP, Stammers DK (2007) J Med Chem 50:2301

    Article  CAS  Google Scholar 

  9. Nunrium P, Kuno M, Saen-oon S, Hannongbua S (2005) Chem Phys Lett 405:198

    Article  CAS  Google Scholar 

  10. Saen-oon S, Kuno M, Hannongbua S (2005) Proteins 61:859

    Article  CAS  Google Scholar 

  11. Mei Y, He X, Xiang Y, Zhang DW, Zhang JZH (2005) Proteins 59:489

    Article  CAS  Google Scholar 

  12. He X, Mei Y, Xiang Y, Zhang DW, Zhang JZH (2005) Proteins 61:423

    Article  CAS  Google Scholar 

  13. Zhao Y, Truhlar DG (2008) Theor Chem Account 120:215

    Article  CAS  Google Scholar 

  14. Zhao Y, Truhlar DG (2008) Account Chem Res 41:157

    Article  CAS  Google Scholar 

  15. Gu J, Wang J, Leszczynski J, Xie Y, Schaefer HF III (2008) Chem Phys Lett 459:164

    Article  CAS  Google Scholar 

  16. Mourik TV (2008) J Chem Theory Comput 4:1610

    Article  Google Scholar 

  17. Sitkoff D, Lockhart DJ, Sharp KA, Honig B (1994) Biophys J 67:2251

    Article  CAS  Google Scholar 

  18. Baeten A, Maes D, Geerlings P (1998) J Theor Biol 195:27

    Article  CAS  Google Scholar 

  19. Roos G, Messens J, Loverix S, Wyns L, Geerlings P (2004) J Phys Chem B 108:17216

    Article  CAS  Google Scholar 

  20. Kang YK, Scheraga HA (2008) J Phys Chem B 112:5470

    Article  CAS  Google Scholar 

  21. Martin F, Zipse H (2005) J Comput Chem 26:97

    Article  CAS  Google Scholar 

  22. Tsuzuki S, Lüthi HP (2001) J Chem Phys 114:3949

    Article  CAS  Google Scholar 

  23. Kuno M, Hannongbua S, Morokuma K (2003) Chem Phys Lett 380:456

    Article  CAS  Google Scholar 

  24. Saparpakorn P, Hannongbua S, Rognan D (2006) SAR QSAR Environ Res 17:183

    Article  CAS  Google Scholar 

  25. SYBYL 7.2, TRIPOS, Assoc., Inc., St. Louis, MO

  26. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA Jr, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2004) Gaussian 03. Gaussian, Inc., Wallingford

    Google Scholar 

Download references

Acknowledgments

The authors are grateful to the Thailand Research Fund (RTA53800010, DBG5180022, MRG5080267) and Faculty of Science (ScRF), Kasetsart University for the research grant. Center of Nanotechnology at Kasetsart University, Laboratory for Computational and Applied Chemistry (LCAC), National Center of Excellence for Petroleum, Petrochemicals, and Advanced Materials (NCE-PPAM), and Large Scale Simulation Research Laboratory (LSR)/NECTEC, ASEA-Uninet and the University of Vienna are also gratefully acknowledged for research facilities and computing resources.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok, 10900, Thailand

    Patchreenart Saparpakorn & Supa Hannongbua

  2. Center of Nanotechnology KU, Kasetsart University, Bangkok, 10900, Thailand

    Patchreenart Saparpakorn & Supa Hannongbua

  3. International Center for Science and Engineering Programs (ICSEP), Faculty of Science and Engineering, Waseda University, Tokyo, 169-8555, Japan

    Patchreenart Saparpakorn

  4. Institute of Theoretical Chemistry, University of Vienna, Vienna, Austria

    Peter Wolschann & Alfred Karpfen

  5. Department of Chemistry, Faculty of Science, Ubonratchathani University, Ubonratchathani, 34190, Thailand

    Pornpan Pungpo

Authors
  1. Patchreenart Saparpakorn
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  2. Peter Wolschann
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  3. Alfred Karpfen
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  4. Pornpan Pungpo
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  5. Supa Hannongbua
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Correspondence to Patchreenart Saparpakorn.

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Saparpakorn, P., Wolschann, P., Karpfen, A. et al. Systematic investigation on the binding of GW420867X as HIV-1 reverse transcriptase inhibitor. Monatsh Chem 142, 961–971 (2011). https://doi.org/10.1007/s00706-011-0497-3

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  • DOI: https://doi.org/10.1007/s00706-011-0497-3

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