Abstract
In the present study, the role of inter-residue interactions in ligand binding and the ligand-receptor interactions were examined. Computational chemistry methods of ligand docking and molecular dynamics simulations were used to study the binding of β-funaltrexamine (β-FNA) and N-methyl-β-funaltrexamine (N-methyl-β-FNA) to μ- and κ-opioid receptors and to the μ-receptor with Lys3036.58Glu mutation. It was found that inter-residue interactions Lys2335.39-Glu3036.58 in the mutant receptor and Lys2275.39-Asp2235.35 in the κ-receptor are more likely to prevent covalent bond formation between β-FNA and the receptor than the ligand-receptor interactions. This emphasizes the importance of inter-residue interactions in ligand binding as well as the effects of point-mutations.
Acknowledgements
This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Contract 173001).
References
Alewijnse, A. E., Timmerman, H., Jacobs, E. H., Smit, M. J., Roovers, E., Cotecchia, S., & Leurs, R. (2000). The effect of mutations in the DRY motif on the constitutive activity and structural instability of the histamine H2 receptor. Molecular Pharmacology, 57, 890-898.Search in Google Scholar
Chen, C., Xue, J. C., Zhu, J., Chen, Y. W., Kunapuli, S., Kim deRiel, J., Yu, L., & Liu-Chen, L. Y. (1995). Characterization ofirreversible binding of β-funaltrexamine to the cloned rat μ-opioidreceptor. Journal of Biological Chemistry, 270,1786617870.10.1074/jbc.270.30.17866Search in Google Scholar
Cox, B. M. (2013). Recent developments in the study of opioid receptors. Molecular Pharmacology, 83, 723-728. DOI:10.1124/mol.112.083279.10.1124/mol.112.083279Search in Google Scholar
Cui, X., Yeliseev, A., & Liu, R. (2013). Ligand interaction, binding site and G protein activation of the mu opioid receptor. European Journal of Pharmacology, 702, 309—315. DOI: 10.1016/j.ejphar.2013.01.060.10.1016/j.ejphar.2013.01.060Search in Google Scholar
DiMattio, K. M., Chen, C., Shi, L., & Liu-Chen, L. Y. (2015). K3036’58 in the μ opioid (MOP) receptor is important in conferring selectivity for covalent binding of β-funaltrexamine (β-FNA). European Journal of Pharmacology, 748, 93—100. DOI: 10.1016/j.ejphar.2014.11.028.10.1016/j.ejphar.2014.11.028Search in Google Scholar
Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Montgomery, J. A. Jr., Vreven, T., Kudin, K. N., Burant, J. C., Millam, J. M., Iyengar, S. S., Tomasi, J., Barone, V., Mennucci, B., Cossi, M., Scalmani, G., Rega, N., Petersson, G.A., 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, J. E., Hratchian, H. P., Cross, J. B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R. E., Yazyev, O., Austin, A. J., Cammi, R., Pomelli, C., Ochterski J. W., Ayala P. Y., Morokuma, K., Voth G. A., Salvador, P., Dannenberg, J. J., Zakrzewski, V. G., Dapprich, S., Daniels, A. D., Strain, M.C., Farkas, O., Malick, D. K., Rabuck, A., Raghavachari, D. K., Foresman, J. B., Ortiz, J. V., Cui, Q., Baboul, A. G., Clifford, S., Cioslowski, J., Stefanov, B. B., Liu, G., Liashenko, A., Piskorz, P., Komaromi, I., Martin, R. L., Fox, D. J., Keith, T., Al-Laham, M. A., Peng, C. Y., Nanayakkara, A., Challacombe, M., Gill, P. M. W., Johnson, B. Chen, W., Wong, M. W., Gonzalez, C., & Pople, J. A. (2004). Gaussian 03, Revision C.02 [computer software]. Wallingford, CT, USA: Gaussian.Search in Google Scholar
Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD – visual molecular dynamics. Journal of Molecular Graphics, 14, 3338. DOI: 10.1016/0263-7855(96)00018-5.10.1016/-0263-7855-(96)-00018-5Search in Google Scholar
Huang, W., Manglik, A., Venkatakrishnan, A. J., Laeremans, T., Feinberg, E. N., Sanborn, A. L., Kato, H. E., Livingston, K. E., Thorsen, T. S., Kling, R. C., Granier, S., Gmeiner, P., Husbands, S. M., Traynor, J. R., Weis, W. I., Steyaert, J., Dror, R. O., & Kobilka, B. K. (2015). Structural insights into mu-opioid receptor activation. Nature, 524, 315-321. DOI: 10.1038/nature14886.10.1038/nature14886Search in Google Scholar
Jacobson, K. A., & Costanzi, S. (2012). New insights for drug design from the X-ray crystallographic structures of g-protein-coupled receptors. Molecular Pharmacology, 82, 361371. DOI: 10.1124/mol.112.079335.10.1124/mol.112.079335Search in Google Scholar
Jafurulla, M., Tiwari, S., & Chattopadhyay, A. (2011). Identification of cholesterol recognition amino acid consensus (CRAC) motif in G-protein coupled receptors. Biochemical and Biophysical Research Communications, 404, 569-573. DOI: 10.1016/j.bbrc.2010.12.031.10.1016/j.bbrc.2010.12.031Search in Google Scholar
Kane, B. E., Svensson, B., & Ferguson, D. M. (2006). Molecular recognition of opioid receptor ligands. The AAPS Journal, 8, E126-E137. DOI: 10.1208/aapsj080115.10.1208/aapsj080115Search in Google Scholar
Law, R. J. (2004). Explicit membrane protein simulations in NAMD/VMD. Retrieved November 21, 2015, from http://users.mccammon.ucsd.edu/~rlaw/ctbp_workshop_rlaw.htmSearch in Google Scholar
MacKerell, A. D., Jr., Banavali, N., & Foloppe, N. (2001). Development and current status of the CHARMM force field for nucleic acids. Biopolymers, 56, 257-265. DOI: 10.1002/1097-0282(2000)56:4 257::AID-BIP10029 3.0.CO;2-W.10.1002/1097-0282(2000)56:4257::AID-BIP100293.0.CO;2-WSearch in Google Scholar
Manglik, A., Kruse, A. C., Kobilka, T. S., Thian, F. S., Mathiesen, J. M., Sunahara, R. K., Pardo, L., Weis, W. I., Kobilka, B. K., & Granier, S. (2012). Crystal structure of the μ-opioid receptor bound to a morphinan antagonist. Nature, 485, 321326. DOI: 10.1038/nature10954.10.1038/nature10954Search in Google Scholar PubMed PubMed Central
Mohamed, M. S., Larson, D. L., Takemori, A. E., & Portoghese, P. S. (1986). Activity of N-methyl-alpha- and betafunaltrexamine at opioid receptors. Journal of Medicinal Chemistry, 29, 1551-1553. DOI: 10.1021/jm00158a043.10.1021/jm00158a043Search in Google Scholar PubMed
Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30, 27852791. DOI: 10.1002/jcc.21256.10.1002/jcc.21256Search in Google Scholar PubMed PubMed Central
Noori, H. R., Mucksch, C., & Urbassek, H. M. (2014). A structural feature of the non-peptide ligand interactions with mice μ-opioid receptors. Current Computer-Aided Drug Design, 10, 354-360. DOI: 10.2174/1573409910666141031093 504.10.2174/1573409910666141031093 504Search in Google Scholar
Petersson, G. A., Bennett, A., Tensfeldt, T. G., Al-Laham, M. A., Shirley, W. A., & Mantzaris, J. (1988). A complete basis set model chemistry. I. The total energies of closed-shell atoms and hydrides of the first-row atoms. Journal of Chemical Physics, 89, 2193-2198. DOI: 10.1063/1.455064.10.1063/1.455064Search in Google Scholar
Petersson, G. A., & Al-Laham, M. A. (1991). A complete basis set model chemistry. II. Open-shell systems and the total energies of the first-row atoms. Journal of Chemical Physics, 94, 6081-6090. DOI: 10.1063/1.460447.10.1063/1.460447Search in Google Scholar
Phillips, J. C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R. D., Kale, L., & Schulten, K. (2005). Scalable molecular dynamics with NAMD. Journal of Computational Chemistry, 26, 1781-1802. DOI: 10.1002/jcc.20289.10.1002/jcc.20289Search in Google Scholar PubMed PubMed Central
Sanner, M. F. (1999). Python: A programming language for software integration and development. Journal of Molecular Graphics and Modeling, 17, 57-61.Search in Google Scholar
Singh, S., Foley, J., Zhang, H., & Farber, J. (2010). The DRF motif in CXCR6 is important for selectivity among G-proteins in receptor signaling, which is cell-type specific. The Journal of Immunology, 184, 133.1.Search in Google Scholar
Tam, S. W., & Liu-Chen, L. Y. (1986). Reversible and irreversible binding of funaltrexamine to mu, delta and kappa opioid receptors in guinea pig brain membranes. Journal of Pharmacology and Experimental Therapeutics, 239, 351357.Search in Google Scholar
Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry, 31, 455-461. DOI: 10.1002/jcc.21334.10.1002/jcc.21334Search in Google Scholar PubMed PubMed Central
Vanommeslaeghe, K., & MacKerell, A. D., Jr. (2012). Automation of the CHARMM General Force Field (CGenFF) I: bond perception and atom typing. Journal of Chemical Information and Modeling, 52, 3144-3154. DOI: 10.1021/ci300363c.10.1021/ci300363cSearch in Google Scholar PubMed PubMed Central
Vanommeslaeghe, K., Raman, E. P., & MacKerell, A. D., Jr.(2012). Automation of the CHARMM General Force Field (CGenFF) II: Assignment of bonded parameters and partial atomic charges. Journal of Chemical Information and Modeling, 52, 3155-3168. DOI: 10.1021/ci3003649.10.1021/ci3003649Search in Google Scholar PubMed PubMed Central
Vardy, E., Mosier, P. D., Frankowski, K. J., Wu, H., Katritch, V., Westkaemper, R. B., Aubé, J., Stevens, R. C., & Roth, B. L. (2013). Chemotype-selective modes of action of κ-opioid receptor agonists. Journal of Biological Chemistry, 288, 34470-34483. DOI: 10.1074/jbc.m113.515668.10.1074/jbc.m113.515668Search in Google Scholar
Wu, H., Wacker, D., Mileni, M., Katritch, V., Han, G. W., Vardy, E., Liu, W., Thompson, A. A., Huang, X. P., Carroll, F. I., Mascarella, S. W., Westkaemper, R. B., Mosier, P. D., Roth, B. L., Cherezov, V., & Stevens, R. C. (2012). Structure of the human κ-opioid receptor in complex with JDTic. Nature, 485, 327-332. DOI: 10.1038/nature10939.10.1038/nature10939Search in Google Scholar PubMed PubMed Central
Zhang, Y., Sham, Y. Y., Rajamani, R., Gao, J., & Portoghese, P. S. (2005). Homology modeling and molecular dynamics simulations of the μ-opioid receptor in a membrane-aqueous system. ChemBioChem, 6, 853-859. DOI: 10.1002/cbic.200400207.10.1002/cbic.200400207Search in Google Scholar PubMed
© 2016 Institute of Chemistry, Slovak Academy of Sciences
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