Molecular Mechanics/Coarse-Grained Simulations as a Structural Prediction Tool for GPCRs/Ligand Complexes

In Silico Drug Discovery and Design: Theory, Methods, Challenges, and Applications

Volumn , Issue , 2015, Pages 337-352

  Musiani, Francesco ^a   Giorgetti, Alejandro ^b,c   Carloni, Paolo ^d,e,f  

^a SISSA   (Italy)

^b Institute for Advanced imulation IAS 5 and   (Italy)

^c UNIVERSITY OF VERONA   (Italy)

^d Brain Behaviour   (Germany)

^e FORSCHUNGSZENTRUM JÜLICH   (Germany)

^f German Research School for Simulation Sciences GmbH ^*  (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85039772447     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1201/b18799-19     Document Type: Chapter

References (69)

1. Angel, T. E., M. R. Chance, and K. Palczewski. 2009. Conserved waters mediate structural and functional activation of family A (rhodopsin-like) G protein-coupled receptors. Proc. Natl. Acad. Sci. USA 106(21): 8555–8560.
2. Audet, M. and M. Bouvier. 2012. Restructuring G-protein-coupled receptor activation. Cell 151(1): 14–23.
3. Berendsen, H. J. C., D. van der Spoel, and R. van Drunen. 1995. GROMACS: A message- passing parallel molecular dynamics implementation. Comput. Phys. Commun. 91(1–3): 43–56.
4. Berweger, C. D., W. F. van Gunsteren, and F. Müller-Plathe. 1995. Force field parametrization by weak coupling. Re-engineering SPC water. Chem. Phys. Lett. 232(5– 6): 429–436.
5. Bhattacharya, S., G. Subramanian, S. Hall, J. Lin, A. Laoui, and N. Vaidehi. 2010. Allosteric antagonist binding sites in class B GPCRs: Corticotropin receptor 1. J. Comput. Aid. Mol. Des. 24(8): 659–674.
6. Biarnes, X., A. Marchiori, A. Giorgetti et al. 2010. Insights into the binding of Phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor. PLoS One 5(8): e12394.
7. Bjarnadottir, T. K., D. E. Gloriam, S. H. Hellstrand, H. Kristiansson, R. Fredriksson, and H. B. Schioth. 2006. Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse. Genomics 88(3): 263–273.
8. Brockhoff, A., M. Behrens, M. Y. Niv, and W. Meyerhof. 2010. Structural requirements of bitter taste receptor activation. Proc. Natl. Acad. Sci. USA 107(24): 11110–11115.
9. Camacho, C. J. 2005. Modeling side-chains using molecular dynamics improve recognition of binding region in CAPRI targets. Proteins 60(2): 245–251.
10. Carlsson, J., R. G. Coleman, V. Setola et al. 2011. Ligand discovery from a dopamine D3 receptor homology model and crystal structure. Nat. Chem. Biol. 7(11): 769–778.
11. Cherezov, V., D. M. Rosenbaum, M. A. Hanson et al. 2007. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318(5854): 1258–1265.
12. Costanzi, S. 2013. Modeling G protein-coupled receptors and their interactions with ligands. Curr. Opin. Struct. Biol. 23(2): 185–190.
13. de Graaf, C. and D. Rognan. 2009. Customizing G Protein-coupled receptor models for structure-based virtual screening. Curr. Pharm. Des. 15(35): 4026–4048.
14. Dorsam, R. T. and J. S. Gutkind. 2007. G-protein-coupled receptors and cancer. Nat. Rev. Cancer 7(2): 79–94.
15. Dror, R. O., A. C. Pan, D. H. Arlow et al. 2011. Pathway and mechanism of drug binding to G-protein-coupled receptors. Proc. Natl. Acad. Sci. USA 108(32): 13118–13123.
16. Eswar, N., B. Webb, M. A. Marti-Renom et al. 2007. Comparative protein structure modeling using MODELLER. Curr. Protoc. Protein Sci. Chapter 2: Unit 2 9.
17. Fallmar, H., H. Akerberg, H. Gutierrez-de-Teran, I. Lundell, N. Mohell, and D. Larhammar. 2011. Identification of positions in the human neuropeptide Y/ peptide YY receptor Y2 that contribute to pharmacological differences between receptor subtypes. Neuropeptides 45(4): 293–300.
18. Garcia-Perez, J., P. Rueda, J. Alcami et al. 2011. Allosteric model of maraviroc binding to CC chemokine receptor 5 (CCR5). J. Biol. Chem. 286(38): 33409–33421.
19. Gatica, E. A. and C. N. Cavasotto. 2012. Ligand and decoy sets for docking to G protein- coupled receptors. J. Chem. Inf. Model. 52(1): 1–6.
20. Go, N. and H. Abe. 1981. Noninteracting local-structure model of folding and unfolding transition in globular proteins. I. Formulation. Biopolymers 20(5): 991–1011.
21. Gurevich, V. V. and E. V. Gurevich. 2008. GPCR monomers and oligomers: It takes all kinds. Trends Neurosci. 31(2): 74–81.
22. Gutierrez-de-Teran, H., X. Bello, and D. Rodriguez. 2013. Characterization of the dynamic events of GPCRs by automated computational simulations. Biochem. Soc. Trans. 41(1): 205–212.
23. Hess, B., C. Kutzner, D. van der Spoel, and E. Lindahl. 2008. GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 4(3): 435–447.
24. Hollenstein, K., J. Kean, A. Bortolato et al. 2013. Structure of class B GPCR corticotropin- releasing factor receptor 1. Nature 499(7459): 438–443.
25. Ivanov, A. A., D. Barak, and K. A. Jacobson. 2009. Evaluation of homology modeling of G-protein-coupled receptors in light of the A2A adenosine receptor crystallographic structure. J. Med. Chem. 52(10): 3284–3292.
26. Khafizov, K., C. Anselmi, A. Menini, and P. Carloni. 2007. Ligand specificity of odorant receptors. J. Mol. Model. 13(3): 401–409.
27. Kothandan, G., C. G. Gadhe, and S. J. Cho. 2012. Structural insights from binding poses of CCR2 and CCR5 with clinically important antagonists: A combined in silico study. PLoS One 7(3): e32864.
28. Kufareva, I., M. Rueda, V. Katritch, R. C. Stevens, and R. Abagyan. 2011. Status of GPCR modeling and docking as reflected by community-wide GPCR dock 2010 assessment. Structure 19(8): 1108–1126.
29. Leguebe, M., C. Nguyen, L. Capece, Z. Hoang, A. Giorgetti, and P. Carloni. 2012. Hybrid molecular mechanics/coarse-grained simulations for structural prediction of G-protein coupled receptor/ligand complexes. PLoS One 7(10): e47332.
30. Levit, A., D. Barak, M. Behrens, W. Meyerhof, and M. Y. Niv. 2012. Homology modelassisted elucidation of binding sites in GPCRs. Methods Mol. Biol. 914: 179–205.
31. Lindahl, E., B. Hess, and D. van der Spoel. 2001. GROMACS 3.0: A package for molecular simulation and trajectory analysis. J. Mol. Model. 7(8): 306–317.
32. Marchiori, A., L. Capece, A. Giorgetti et al. 2013. Coarse-grained/molecular mechanics of the TAS2R38 bitter taste receptor: Experimentally-validated detailed structural prediction of agonist binding. PLoS One 8(5): e64675.
33. Michino, M., E. Abola, GPCR Dock 2008 participants et al. 2009. Community-wide assessment of GPCR structure modelling and ligand docking: GPCR Dock 2008. Nature Rev. 8: 455–463.
34. Mobarec, J. C., R. Sanchez, and M. Filizola. 2009. Modern homology modeling of G-protein coupled receptors: Which structural template to use? J. Med. Chem. 52(16): 5207–5216.
35. Murakami, M. and T. Kouyama. 2008. Crystal structure of squid rhodopsin. Nature 453(7193): 363–367.
36. Nadler, W., A. T. Brunger, K. Schulten, and M. Karplus. 1987. Molecular and stochastic dynamics of proteins. Proc. Natl. Acad. Sci. USA 84(22): 7933–7937.
37. Neri, M., C. Anselmi, M. Cascella, A. Maritan, and P. Carloni. 2005. Coarse-grained model of proteins incorporating atomistic detail of the active site. Phys. Rev. Lett. 95(21): 218102.
38. Neri, M., M. Baaden, V. Carnevale, C. Anselmi, A. Maritan, and P. Carloni. 2008. Microseconds dynamics simulations of the outer-membrane protease T. Biophys. J. 94(1): 71–78.
39. Niv, M. Y. and M. Filizola. 2008. Influence of oligomerization on the dynamics of G-protein coupled receptors as assessed by normal mode analysis. Proteins 71(2): 575–586.
40. Niv, M. Y., L. Skrabanek, M. Filizola, and H. Weinstein. 2006. Modeling activated states of GPCRs: The rhodopsin template. J. Comput. Aid. Mol. Des. 20(7–8): 437–448.
41. Nygaard, R., L. Valentin-Hansen, J. Mokrosinski, T. M. Frimurer, and T. W. Schwartz. 2010. Conserved water-mediated hydrogen bond network between TM-I, -II, -VI, and -VII in 7TM receptor activation. J. Biol. Chem. 285(25): 19625–19636.
42. Osher, S. and J. A. Sethian. 1988. Fronts propagating with curvature-dependent speed–algorithms based on Hamilton-Jacobi formulations. J. Comput. Phys. 79(1): 12–49.
43. Overington, J. P., B. Al-Lazikani, and A. L. Hopkins. 2006. How many drug targets are there? Nat. Rev. Drug. Discov. 5(12): 993–996.
44. Petrel, C., A. Kessler, P. Dauban, R. H. Dodd, D. Rognan, and M. Ruat. 2004. Positive and negative allosteric modulators of the Ca2+ sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain. J. Biol. Chem. 279(18): 18990–18997.
45. Pronk, S., S. Pall, R. Schulz et al. 2013. GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 29(7): 845–854.
46. Provasi, D., A. Bortolato, and M. Filizola. 2009. Exploring molecular mechanisms of ligand recognition by opioid receptors with metadynamics. Biochemistry 48(42): 10020–10029.
47. Provasi, D., J. M. Johnston, and M. Filizola. 2010. Lessons from free energy simulations of delta-opioid receptor homodimers involving the fourth transmembrane helix. Biochemistry 49(31): 6771–6776.
48. Rayan, A. 2010. New vistas in GPCR 3D structure prediction. J. Mol. Model. 16(2): 183–191.
49. Rodriguez, D., A. Pineiro, and H. Gutierrez-de-Teran. 2011. Molecular dynamics simulations reveal insights into key structural elements of adenosine receptors. Biochemistry 50(19): 4194–4208.
50. Rosenbaum, D. M., S. G. Rasmussen, and B. K. Kobilka. 2009. The structure and function of G-protein-coupled receptors. Nature 459(7245): 356–363.
51. Scarabelli, G., D. Provasi, A. Negri, and M. Filizola. 2014. Bioactive conformations of two seminal delta opioid receptor penta-peptides inferred from free-energy profiles. Biopolymers 101(1): 21–27.
52. Schoneberg, T., A. Schulz, H. Biebermann, T. Hermsdorf, H. Rompler, and K. Sangkuhl. 2004. Mutant G-protein-coupled receptors as a cause of human diseases. Pharmacol. Ther. 104(3): 173–206.
53. Scott, W. R. P., P. H. Hunenberger, I. G. Tironi et al. 1999. The GROMOS biomolecular simulation program package. J. Phys. Chem. A 103(19): 3596–3607.
54. Siu, F. Y., M. He, C. de Graaf et al. 2013. Structure of the human glucagon class B G-protein-coupled receptor. Nature 499(7459): 444–449.
55. Slack, J. P., A. Brockhoff, C. Batram et al. 2010. Modulation of bitter taste perception by a small molecule hTAS2R antagonist. Curr. Biol. 20(12): 1104–1109.
56. Sprang, S. R. 2011. Cell signalling: Binding the receptor at both ends. Nature 469(7329): 172–173.
57. Stevens, R. C., V. Cherezov, V. Katritch et al. 2013. The GPCR Network: A large-scale collaboration to determine human GPCR structure and function. Nat. Rev. Drug Discov. 12(1): 25–34.
58. Sun, L. and R. D. Ye. 2012. Role of G protein-coupled receptors in inflammation. Acta Pharmacol. Sin. 33(3): 342–350.
59. Topiol, S. and M. Sabio. 2009. X-ray structure breakthroughs in the GPCR transmembrane region. Biochem. Pharmacol. 78(1): 11–20.
60. Tramontano, A., D. Cozzetto, A. Giorgetti, and D. Raimondo. 2008. The assessment of methods for protein structure prediction. Methods Mol. Biol. 413: 43–57.
61. Van Der Spoel, D., E. Lindahl, B. Hess, G. Groenhof, A. E. Mark, and H. J. C. Berendsen. 2005. GROMACS: Fast, flexible, and free. J. Comput. Chem. 26(16): 1701–1718.
62. Vanni, S., M. Neri, I. Tavernelli, and U. Rothlisberger. 2009. Observation of “ionic lock” formation in molecular dynamics simulations of wild-type beta 1 and beta 2 adrenergic receptors. Biochemistry 48(22): 4789–4797.
63. Vanni, S., M. Neri, I. Tavernelli, and U. Rothlisberger. 2010. A conserved protonationinduced switch can trigger “ionic-lock” formation in adrenergic receptors. J. Mol. Biol. 397(5): 1339–1349.
64. Vanni, S., M. Neri, I. Tavernelli, and U. Rothlisberger 2011. Predicting novel binding modes of agonists to beta adrenergic receptors using all-atom molecular dynamics simulations. PLoS Comput. Biol. 7(1): e1001053.
65. Venkatakrishnan, A. J., X. Deupi, G. Lebon, C. G. Tate, G. F. Schertler, and M. M. Babu. 2013. Molecular signatures of G-protein-coupled receptors. Nature 494(7436): 185–194.
66. Vilar, S., G. Ferino, S. S. Phatak, B. Berk, C. N. Cavasotto, and S. Costanzi. 2011. Docking-based virtual screening for ligands of G protein-coupled receptors: Not only crystal structures but also in silico models. J. Mol. Graphics Modell. 29(5): 614–623.
67. Wang, C., H. Wu, V. Katritch et al. 2013. Structure of the human smoothened receptor bound to an antitumour agent. Nature 497(7449): 338–343.
68. Yarnitzky, T., A. Levit, and M. Y. Niv. 2010. Homology modeling of G-protein-coupled receptors with x-ray structures on the rise. Curr. Opin. Drug Discov. Devel. 13(3): 317–325.
69. Yuan, S., H. Vogel, and S. Filipek. 2013. The role of water and sodium ions in the activation of the mu-opioid receptor. Angew. Chem. Int. Ed. Engl. 52(38): 10112–10115.