431
Views
13
CrossRef citations to date
0
Altmetric
Articles

Computational modeling of human coreceptor CCR5 antagonist as a HIV-1 entry inhibitor: using an integrated homology modeling, docking, and membrane molecular dynamics simulation analysis approach

, &
Pages 1251-1276 | Received 23 Jun 2012, Accepted 07 Sep 2012, Published online: 16 Nov 2012

References

  • Aalten, D. M. F., Bywater, R., Findlay, J. B. C., Hendlich, M., Hooft, R. W. W., & Vriend, G. (1996). PRODRG, a program for generating molecular topologies and unique molecular descriptors from coordinates of small molecules. Journal of Computer-Aided Molecular Design,10, 255–262.
  • Abdelwahab, S. F., Cocchi, F., Bagley, K. C., Kamin-Lewis, R., Gallo, R. C., DeVico, A., & Lewis, G. K. (2003). HIV-1-suppressive factors are secreted by CD4+ T cells during primary immune responses. Proceedings of the National Academy of Sciences of the United States of America,100, 15006–15010.
  • Afantitis, A., Melagraki, G., Sarimveis, H., Koutentis, P. A., Markopoulos, J., & Igglessi-Markopoulou, O. (2006). Investigation of substituent effect of 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides on CCR5 binding affinity using QSAR and virtual screening techniques. Journal of Computer-Aided Molecular Design,20, 83–95.
  • Aher, Y. D., Agrawal, A., Bharatam, P. V., & Garg, P. (2007). 3D-QSAR studies of substituted 1-(3,3-diphenylpropyl)-piperidinyl amides and ureas as CCR5 receptor antagonists. Journal of Molecular Modeling,13, 519–529.
  • Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990). Basic local alignment search tool. Journal of Molecular Biology,215, 403–410.
  • Andrianov, A. M. (2008). Computational anti-AIDS drug design based on the analysis of the specific interactions between immunophilins and the HIV-1 gp120 V3 loop. Application to the FK506-binding protein. Journal of Biomolecular Structure & Dynamics,26, 49–56.
  • Andrianov, A. M., & Anishchenko, I. V. (2009). Computational model of the HIV-1 subtype A V3 loop: Study on the conformational mobility for structure-based anti-AIDS drug design. Journal of Biomolecular Structure & Dynamics,27, 179–193.
  • Baldwin, J. M., Schertler, G. F. X., & Unger, V. M. (1997). An alpha-carbon template for the transmembrane helices in the rhodopsin family of G-protein-coupled receptors. Journal of Molecular Biology,272, 144–164.
  • Barber, C. G. (2004). CCR5 antagonists for the treatment of HIV. Current Opinion in Investigational Drugs,5, 851–861.
  • Barre-Sinoussi, F., Chermann, J. C., Rey, F., Nugeyre, M. T., Chamaret, S., Gruest, J., & Rouzioux, C. (1983). Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science,220, 868–871.
  • Berendsen, H. J. C., Postma, J. P. M., Van Gunsteren, W. F., DiNola, A., & Haak, J. R. (1984). Molecular dynamics with coupling to an external bath. The Journal of Chemical Physics,81, 3684–3690.
  • Bhargavi, K., Kalyan Chaitanya, P., Ramasree, D., Vasavi, M., Murthy, D. K., & Uma, V. (2010). Homology modeling and docking studies of human Bcl-2L10 protein. Journal of Biomolecular Structure & Dynamics,28, 379–391.
  • Billick, E., Seibert, C., Pugach, P., Ketas, T., Trkola, A., Endres, M. J., & Kuhmann, S. E. (2004). The differential sensitivity of human and rhesus macaque CCR5 to small-molecule inhibitors of human immunodeficiency virus type 1 entry is explained by a single amino acid difference and suggests a mechanism of action for these inhibitors. Journal of Virology,78, 4134–4144.
  • Blanpain, C., Lee, B., Vakili, J., Doranz, B. J., Govaerts, C., Migeotte, I., & Doms, R. W. (1999). Extracellular cysteines of CCR5 are required for chemokine binding, but dispensable for HIV-1 coreceptor activity. Journal of Biological Chemistry,274, 18902–18908.
  • Carrieri, A., Pérez Nueno, V. I., Fano, A., Pistone, C., Ritchie, D. W., & Teixidó, J. (2009). Biological profiling of anti-HIV agents and insight into ccr5 antagonist binding using in silico techniques. ChemMedChem,4, 1153–1163.
  • Castonguay, L. A., Weng, Y., Adolfsen, W., Di Salvo, J., Kilburn, R., Caldwell, C. G., & DeMartino, J. A. (2003). Binding of 2-aryl-4-(piperidin-1-yl) butanamines and 1,3,4-trisubstituted pyrrolidines to human CCR5: A molecular modeling-guided mutagenesis study of the binding pocket. Biochemistry,42, 1544–1550.
  • Coffin, J., Haase, A., Levy, J. A., Montagnier, L., Oroszlan, S., Teich, N., & Vogt, P. (1986). What to call the AIDS virus?Nature,321, 10.
  • Colovos, C., & Yeates, T. O. (1993). Verification of protein structures: Patterns of nonbonded atomic interactions. Protein Science,2, 1511–1519.
  • da Cunha, E. F., Mancini, D. T., & Ramalho, T. C. (2012). Molecular modeling of the Toxoplasma gondii adenosine kinase inhibitors. Medicinal Chemistry Research,21, 590–600.
  • Darden, T., York, D., & Pedersen, L. (1993). Particle mesh Ewald: An Nlog (N) method for Ewald sums in large systems. The Journal of Chemical Physics,98, 10089–10092.
  • Dorr, P., Westby, M., Dobbs, S., Griffin, P., Irvine, B., Macartney, M., & Perros, M. (2005). Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrobial Agents and Chemotherapy,49, 4721–4732.
  • Dragic, T., Trkola, A., Thompson, D. A. D., Cormier, E. G., Kajumo, F. A., Maxwell, E., & Sakmar, T. P. (2000). A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proceedings of the National Academy of Sciences of the United States of America,97, 5639–5644.
  • Eswar, N., John, B., Mirkovic, N., Fiser, A., Ilyin, V. A., Pieper, U., & Yerkovich, B. (2003). Tools for comparative protein structure modeling and analysis. Nucleic Acids Research,31, 3375–3380.
  • Fackler, O. T., & Peterlin, B. M. (2000). Endocytic entry of HIV-1. Current Biology,10, 1005–1008.
  • Fano, A., Ritchie, D. W., & Carrieri, A. (2006). Modeling the structural basis of human CCR5 chemokine receptor function: From homology model building and molecular dynamics validation to agonist and antagonist docking. Journal of Chemical Information and Modeling,46, 1223–1235.
  • Furtado, M. R., Callaway, D. S., Phair, J. P., Kunstman, K. J., Stanton, J. L., Macken, C. A., & Wolinsky, S. M. (1999). Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy. New England Journal of Medicine,340, 1614–1622.
  • Gadhe, C. G., Lee, S. H., Madhavan, T., Kothandan, G., Choi, D. B., & Cho, S. J. (2010). Ligand based CoMFA; CoMSIA and HQSAR analysis of CCR5 antagonists. Bulletin of the Korean Chemical Society,31, 2761–2770.
  • Genoud, S., Kajumo, F., Guo, Y., Thompson, D., & Dragic, T. (1999). CCR5-mediated human immunodeficiency virus entry depends on an amino-terminal gp120-binding site and on the conformational integrity of all four extracellular domains. Journal of Virology,73, 1645–1648.
  • Govaerts, C., Bondue, A., Springael, J. Y., Olivella, M., Deupi, X., Le Poul, E., & Blanpain, C. (2003). Activation of CCR5 by chemokines involves an aromatic cluster between transmembrane helices 2 and 3. Journal of Biological Chemistry,278, 1892–1903.
  • Guimarães, A. P., Oliveira, A. A., da Cunha, E. F., Ramalho, T. C., & França, T. C. (2011). Design of new chemotherapeutics against the deadly anthrax disease. Docking and molecular dynamics studies of inhibitors containing pyrrolidine and riboamidrazone rings on nucleoside hydrolase from Bacillus anthracis. Journal of Biomolecular Structure & Dynamics,28, 455–469.
  • Hermans, J., Berendsen, H. J. C., Van Gunsteren, W. F., & Postma, J. P. M. (1984). A consistent empirical potential for water-protein interactions. Biopolymers,23, 1513–1518.
  • Hess, B. (2008). P-LINCS: A parallel linear constraint solver for molecular simulation. Journal of Chemical Theory and Computation,4, 116–122.
  • Hess, B., Kutzner, C., Van Der Spoel, D., & Lindahl, E. (2008). GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation. Journal of Chemical Theory and Computation,4, 435–447.
  • Höltje, H.-D., & Folkers, G. (2003). Small molecule. In R.Mannhold, H.Kubiny, & H.Timmerman (Eds.), Molecular modeling: Basic principles and applications (pp. 9–91). Weinheim: VCH Publishers Inc.
  • Hoover, W. G. (1985). Canonical dynamics: Equilibrium phase-space distributions. Physical Review A,31, 1695–1697.
  • Horuk, R. (1994). Molecular properties of the chemokine receptor family. Trends in Pharmacological Sciences,15, 159–165.
  • Kandt, C., Ash, W. L., & Peter Tieleman, D. (2007). Setting up and running molecular dynamics simulations of membrane proteins. Methods,41, 475–488.
  • Kaushik, S., Mohanty, D., & Surolia, A. (2012). Molecular dynamics simulations on pars intercerebralis major peptide-C (PMP-C) reveal the role of glycosylation and disulfide bonds in its enhanced structural stability and function. Journal of Biomolecular Structure & Dynamics,29, 905–920.
  • Kazmierski, W., Bifulco, N., Yang, H., Boone, L., DeAnda, F., Watson, C., & Kenakin, T. (2003). Recent progress in discovery of small-molecule CCR5 chemokine receptor ligands as HIV-1 inhibitors. Bioorganic & Medicinal Chemistry,11, 2663–2676.
  • Kazmierski, W. M., Peckham, J. P., Maosheng, D., Kenakin, T. P., Stephen, J., Gudmundsson, K. S., & Feldman, P. L. (2005). Recent progress in the discovery of new CCR5 and CXCR4 chemokine receptor antagonists as inhibitors of HIV-1 entry. Part 2. Current Medicinal Chemistry-Anti-Infective Agents,4, 133–152.
  • Kellenberger, E., Springael, J. Y., Parmentier, M., Hachet-Haas, M., Galzi, J. L., & Rognan, D. (2007). Identification of nonpeptide CCR5 receptor agonists by structure-based virtual screening. Journal of Medicinal Chemistry,50, 1294–1303.
  • Kimura, S. R., Tebben, A. J., & Langley, D. R. (2008). Expanding GPCR homology model binding sites via a balloon potential: A molecular dynamics refinement approach. Proteins: Structure, Function, and Bioinformatics,71, 1919–1929.
  • Kondru, R., Zhang, J., Ji, C., Mirzadegan, T., Rotstein, D., Sankuratri, S., & Dioszegi, M. (2008). Molecular interactions of CCR5 with major classes of small-molecule anti-HIV CCR5 antagonists. Molecular Pharmacology,73, 789–800.
  • Kothandan, G., Gadhe, C. G., & Cho, S. J. (2012). Structural insights from binding poses of CCR2 and CCR5 with clinically important antagonists: A combined in silico study. PLoS ONE,7, e32864.
  • Kothandan, G., Gadhe, C. G., Madhavan, T., & Cho, S. J. (2011). Binding site analysis of CCR2 through in silico methodologies: Docking, CoMFA, and CoMSIA. Chemical Biology & Drug Design,78, 161–174.
  • Kwong, P. D., Wyatt, R., Robinson, J., Sweet, R. W., Sodroski, J., & Hendrickson, W. A. (1998). Structure of an HIV gp 120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature,393, 648–659.
  • Laskowski, R. A., MacArthur, M. W., Moss, D. S., & Thornton, J. M. (1993). PROCHECK: A program to check the stereochemical quality of protein structures. Journal of Applied Crystallography,26, 283–291.
  • Lemkul, J. A., Allen, W. J., & Bevan, D. R. (2010). Practical considerations for building GROMOS-Compatible small-molecule topologies. Journal of Chemical Information and Modeling,50, 2221–2235.
  • Li, G., Haney, K. M., Kellogg, G. E., & Zhang, Y. (2009). Comparative docking study of anibamine as the first natural product CCR5 antagonist in CCR5 homology models. Journal of Chemical Information and Modeling,49, 120–132.
  • Liu, R., Paxton, W. A., Choe, S., Ceradini, D., Martin, S. R., Horuk, R., & Landau, N. R. (1996). Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell,86, 367–377.
  • Liu, S., Shi, X., Liu, C., & Sun, Z. (2004). Characterize dynamic conformational space of human CCR5 extracellular domain by molecular modeling and molecular dynamics simulation. Journal of Molecular Structure: Theochem,673, 133–143.
  • Mackewicz, C. E., Barker, E., & Levy, J. A. (1996). Role of beta-chemokines in suppressing HIV replication. Science,274, 1393–1395.
  • Marmor, M., Sheppard, H. W., Donnell, D., Bozeman, S., Celum, C., Buchbinder, S., & Seage, G. R., III (2001). HIV network for prevention trials vaccine preparedness protocol team: Homozygous and heterozygous CCR5-Delta32 genotypes are associated with resistance to HIV infection. Journal of Acquired Immune Deficiency Syndrome,27, 472–481.
  • Meanwell, N. A., & Kadow, J. F. (2003). Inhibitors of the entry of HIV into host cells. Current Opinion In Drug Discovery & Development,6, 451–461.
  • Metz, M., Bourque, E., Labrecque, J., Danthi, S. J., Langille, J., Harwig, C., & Skerlj, R. T. (2012). Prospective CCR5 small molecule antagonist compound design using a combined mutagenesis/modeling approach. Journal of the American Chemical Society,133, 16477–16485.
  • Miyamoto, S., & Kollman, P. A. (1992). SETTLE: An analytical version of the SHAKE and RATTLE algorithm for rigid water models. Journal of Computational Chemistry,13, 952–962.
  • Morris, G. M., Goodsell, D. S., Halliday, R. S., Huey, R., Hart, W. E., Belew, R. K., & Olson, A. J. (1998). Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. Journal of Computational Chemistry,19, 1639–1662.
  • Nagle, J. F. (1993). Area/lipid of bilayers from NMR. Biophysical Journal,64, 1476–1481.
  • Nishikawa, M., Takashima, K., Nishi, T., Furuta, R. A., Kanzaki, N., Yamamoto, Y., & Fujisawa, J. (2005). Analysis of binding sites for the new small-molecule CCR5 antagonist TAK-220 on human CCR5. Antimicrobial Agents and Chemotherapy,49, 4708–4715.
  • Oliveira, A. A., Rennó, M. N., de Matos, C. A., Bertuzzi, M. D., Ramalho, T. C., Fraga, C. A., & França, T. C. (2011). Molecular modeling studies of Yersinia pestis dihydrofolate reductase. Journal of Biomolecular Structure & Dynamics,29, 351–367.
  • Oostenbrink, C., Villa, A., Mark, A. E., & Van Gunsteren, W. F. (2004). A biomolecular force field based on the free enthalpy of hydration and solvation: The GROMOS force-field parameter sets 53A5 and 53A6. Journal of Computational Chemistry,25, 1656–1676.
  • Palani, A., Shapiro, S., Clader, J. W., Greenlee, W. J., Cox, K., Strizki, J., & Baroudy, B. M. (2001). Discovery of 4-[(Z)-(4-bromophenyl)-(ethoxyimino) methyl]-1’-[(2, 4-dimethyl-3-pyridinyl) carbonyl]-4’-methyl-1, 4’-bipiperidine N-oxide (SCH 351125): an orally bioavailable human CCR5 antagonist for the treatment of HIV infection. Journal of Medicinal Chemistry,44, 3339–3342.
  • Palani, A., Shapiro, S., Josien, H., Bara, T., Clader, J. W., Greenlee, W. J., & Baroudy, B. M. (2002). Synthesis, SAR, and biological evaluation of oximino-piperidino-piperidine amides. 1. Orally bioavailable CCR5 receptor antagonists with potent anti-HIV activity. Journal of Medicinal Chemistry,45, 3143–3160.
  • Parrinello, M., & Rahman, A. (1981). Polymorphic transitions in single crystals: A new molecular dynamics method. Journal of Applied Physics,52, 7182–7190.
  • Paterlini, M. G. (2002). Structure modeling of the chemokine receptor CCR5: Implications for ligand binding and selectivity. Biophysical Journal,83, 3012–3031.
  • Piot, P., Bartos, M., Ghys, P. D., Walker, N., & Schwartlander, B. (2001). The global impact of HIV/AIDS. Nature,410, 968–973.
  • Samson, M., Libert, F., Doranz, B. J., Rucker, J., Liesnard, C., Farber, C. M., & Parmentier, M. (1996). Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature,382, 722–725.
  • Sarita, R. P., Kiran, K. M., Bhargavi, K., Vasavi, M., & Uma, V. (2012). Design and synthesis of potent Cyclin C inhibitors. Journal of Bioequivalence & Bioavailability,4, 43.
  • Scott, W. R. P., Hunenberger, P. H., Tironi, I. G., Mark, A. E., Billeter, S. R., Fennen, J., & Van Gunsteren, W. F. (1999). The GROMOS biomolecular simulation program package. The Journal of Physical Chemistry A,103, 3596–3607.
  • Seibert, C., Ying, W., Gavrilov, S., Tsamis, F., Kuhmann, S. E., Palani, A., & Sakmar, T. P. (2006). Interaction of small molecule inhibitors of HIV-1 entry with CCR5. Virology,349, 41–54.
  • Shaheen, F., & Collman, R. G. (2004). Co-receptor antagonists as HIV-1 entry inhibitors. Current Opinion in Infectious Diseases,17, 7–16.
  • Shahlaei, M., Madadkar-Sobhani, A., Mahnam, K., Fassihi, A., Saghaie, L., & Mansourian, M. (2011). Homology modeling of human CCR5 and analysis of its binding properties through molecular docking and molecular dynamics simulation. Biochimica et Biophysica Acta (BBA)-Biomembranes,1808, 802–817.
  • Strader, C. D., Fong, T. M., Tota, M. R., Underwood, D., & Dixon, R. A. F. (1994). Structure and function of G protein-coupled receptors. Annual Review of Biochemistry,63, 101–132.
  • SYBYL 8.1 Tripos International, 1699 South Hanley Rd., St. Louis, Missouri, 63144, USA (2008).
  • Thompson, J. D., Higgins, D. G., & Gibson, T. J. (1994). CLUSTAL W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Research,22, 4673–4680.
  • Torshin, I. Y., Weber, I. T., & Harrison, R. W. (2002). Geometric criteria of hydrogen bonds in proteins and identification of “bifurcated” hydrogen bonds. Protein Engineering,15, 359–363.
  • Tsamis, F., Gavrilov, S., Kajumo, F., Seibert, C., Kuhmann, S., Ketas, T., & Dragic, T. (2003). Analysis of the mechanism by which the small-molecule CCR5 antagonists SCH-351125 and SCH-350581 inhibit human immunodeficiency virus type 1 entry. Journal of Virology,77, 5201–5208.
  • Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A. E., & Berendsen, H. J. C. (2005). GROMACS: Fast, flexible, and free. Journal of Computational Chemistry,26, 1701–1718.
  • Wallace, A. C., Laskowski, R. A., & Thornton, J. M. (1995). LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions. Protein Engineering,8, 127–134.
  • Wang, T., & Duan, Y. (2008). Binding modes of CCR5-targetting HIV entry inhibitors: Partial and full antagonists. Journal of Molecular Graphics and Modelling,26, 1287–1295.
  • Wiederstein, M., & Sippl, M. J. (2007). ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Research,35, 407–410.
  • Wu, B., Chien, E. Y. T., Mol, C. D., Fenalti, G., Liu, W., Katritch, V., & Stevens, R. C. (2010). Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science,330, 1066–1071.
  • Wu, L., Gerard, N. P., Wyatt, R., Choe, H., Parolin, C., Ruffing, N., & Newman, W. (1996). CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature,384, 179–183.
  • Xu, Y., Liu, H., Niu, C., Luo, C., Luo, X., Shen, J., & Jiang, H. (2004). Molecular docking and 3D QSAR studies on 1-amino-2-phenyl-4-(piperidin-1-yl)-butanes based on the structural modeling of human CCR5 receptor. Bioorganic & Medicinal Chemistry,12, 6193–6208.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.