The pathway of ligand entry from the membrane bilayer to a lipid G protein-coupled receptor

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Stanley, Nathaniel ^a   Pardo, Leonardo ^a,b   Fabritiis, Gianni De ^a,c  

^a UNIVERSITAT POMPEU FABRA   (Spain)

^b UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^c INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ICREA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

LIGAND; SPHINGOSINE 1 PHOSPHATE RECEPTOR;

CHEMISTRY; LIPID BILAYER; LIPID METABOLISM; METABOLISM; MOLECULAR DYNAMICS; MOLECULAR MODEL; TRANSPORT AT THE CELLULAR LEVEL;

BIOLOGICAL TRANSPORT; LIGANDS; LIPID BILAYERS; LIPID METABOLISM; MODELS, MOLECULAR; MOLECULAR DYNAMICS SIMULATION; RECEPTORS, LYSOSPHINGOLIPID;

EID: 84960348606     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep22639     Document Type: Article

References (41)

1. Overington, J. P., Al-Lazikani, B. & Hopkins, A. L. How many drug targets are there? Nat. Rev. Drug Discov. 5, 993-996 (2006).
2. Wang, W. et al. Label-free measuring and mapping of binding kinetics of membrane proteins in single living cells. Nat. Chem. 4, 846-853 (2012).
3. Buch, I., Giorgino, T. & De Fabritiis, G. Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations. Proc. Natl. Acad. Sci. 108, 10184-10189 (2011).
4. Dror, R. O. et al. Pathway and mechanism of drug binding to G-protein-coupled receptors. Proc. Natl. Acad. Sci. 108, 13118-13123 (2011).
5. Kruse, A. C. et al. Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature 482, 552-556 (2012).
6. Coleman, J. A., Quazi, F. & Molday, R. S. Mammalian P4-ATPases and ABC transporters and their role in phospholipid transport. Biochim. Biophys. Acta BBA - Mol. Cell Biol. Lipids 1831, 555-574 (2013).
7. Chun, J., Hla, T., Lynch, K. R., Spiegel, S. & Moolenaar, W. H. International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid Receptor Nomenclature. Pharmacol. Rev. 62, 579-587 (2010).
8. Hanson, M. A. et al. Crystal Structure of a Lipid G Protein-Coupled Receptor. Science 335, 851-855 (2012).
9. Gonzalez, A., Cordomi, A., Caltabiano, G. & Pardo, L. Impact of Helix Irregularities on Sequence Alignment and Homology Modeling of G Protein-Coupled Receptors. ChemBioChem 13, 1393-1399 (2012).
10. Buch, I., Harvey, M. J., Giorgino, T., Anderson, D. P. & De Fabritiis, G. High-Throughput All-Atom Molecular Dynamics Simulations Using Distributed Computing. J. Chem. Inf. Model. 50, 397-403 (2010).
11. Dror, R. O. et al. Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs. Nature 503, 295-299 (2013).
12. Provasi, D., Bortolato, A. & Filizola, M. Exploring Molecular Mechanisms of Ligand Recognition by Opioid Receptors with Metadynamics. Biochemistry (Mosc.) 48, 10020-10029 (2009).
13. Hurst, D. P. et al. A lipid pathway for ligand binding is necessary for a cannabinoid G protein-coupled receptor. J. Biol. Chem. 285, 17954-17964 (2010).
14. Doerr, S. & De Fabritiis, G. On-the-Fly Learning and Sampling of Ligand Binding by High-Throughput Molecular Simulations. J. Chem. Theory Comput. (2014), doi: 10.1021/ct400919u.
15. Kohlhoff, K. J. et al. Cloud-based simulations on Google Exacycle reveal ligand modulation of GPCR activation pathways. Nat. Chem. 6, 15-21 (2014).
16. Park, J. H., Scheerer, P., Hofmann, K. P., Choe, H.-W. & Ernst, O. P. Crystal structure of the ligand-free G-protein-coupled receptor opsin. Nature 454, 183-187 (2008).
17. Hildebrand, P. W. et al. A Ligand Channel through the G Protein Coupled Receptor Opsin. PLoS One 4, e4382 (2009).
18. Schmidtke, P., Bidon-Chanal, A., Luque, F. J. & Barril, X. MDpocket: open-source cavity detection and characterization on molecular dynamics trajectories. Bioinforma. Oxf. Engl. 27, 3276-3285 (2011).
19. Gonzalez, A., Perez-Acle, T., Pardo, L. & Deupi, X. Molecular Basis of Ligand Dissociation in β -Adrenergic Receptors. PLoS One 6, e23815 (2011).
20. Bock, A. et al. The allosteric vestibule of a seven transmembrane helical receptor controls G-protein coupling. Nat. Commun. 3, 1044 (2012).
21. Freire, E. Do enthalpy and entropy distinguish first in class from best in class? Drug Discov. Today 13, 869-874 (2008).
22. Bohm, H.-J. & Klebe, G. What Can We Learn from Molecular Recognition in Protein-Ligand Complexes for the Design of New Drugs? Angew. Chem. Int. Ed. Engl. 35, 2588-2614 (1996).
23. Stanley, N., Esteban-Martin, S. & De Fabritiis, G. Kinetic modulation of a disordered protein domain by phosphorylation. Nat. Commun. 5, (2014).
24. Noe, F. et al. Dynamical fingerprints for probing individual relaxation processes in biomolecular dynamics with simulations and kinetic experiments. Proc. Natl. Acad. Sci. 108, 4822-4827 (2011).
25. Harrigan, M. P., Shukla, D. & Pande, V. S. Conserve Water: A Method for the Analysis of Solvent in Molecular Dynamics. J. Chem. Theory Comput. (2015), doi: 10.1021/ct5010017.
26. Chrencik, J. E. et al. Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1. Cell 161, 1633-1643 (2015).
27. Parrill, A. L. et al. Identification of Edg1 Receptor Residues That Recognize Sphingosine 1-Phosphate. J. Biol. Chem. 275, 39379-39384 (2000).
28. Nygaard, R. et al. The Dynamic Process of β 2-Adrenergic Receptor Activation. Cell 152, 532-542 (2013).
29. Perez-Aguilar, J. M., Shan, J., LeVine, M. V., Khelashvili, G. & Weinstein, H. A Functional Selectivity Mechanism at the Serotonin-2A GPCR Involves Ligand-Dependent Conformations of Intracellular Loop 2. J. Am. Chem. Soc. 136, 16044-16054 (2014).
30. Jo, S., Lim, J. B., Klauda, J. B. & Im, W. CHARMM-GUI Membrane Builder for Mixed Bilayers and Its Application to Yeast Membranes. Biophys. J. 97, 50-58 (2009).
31. Humphrey, W., Dalke, A. & Schulten, K. VMD: Visual molecular dynamics. J. Mol. Graph. 14, 33-38 (1996).
32. MacKerell et al. All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins. J Phys Chem B 102, 3586-3616 (1998).
33. Mackerell, A. D., Feig, M. & Brooks, C. L. Extending the treatment of backbone energetics in protein force fields: Limitations of gasphase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations. J. Comput. Chem. 25, 1400-1415 (2004).
34. Vanommeslaeghe, K., Raman, E. P. & MacKerell, A. D. Automation of the CHARMM General Force Field (CGenFF) II: Assignment of bonded parameters and partial atomic charges. J. Chem. Inf. Model. (2012), doi: 10.1021/ci3003649.
35. Vanommeslaeghe, K. & MacKerell, A. D. Automation of the CHARMM General Force Field (CGenFF) I: bond perception and atom typing. J. Chem. Inf. Model. 52, 3144-3154 (2012).
36. Vanommeslaeghe, K. et al. CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM allatom additive biological force fields. J. Comput. Chem. 31, 671-690 (2010).
37. Yu, W., He, X., Vanommeslaeghe, K. & MacKerell, A. D. Extension of the CHARMM general force field to sulfonyl-containing compounds and its utility in biomolecular simulations. J. Comput. Chem. 33, 2451-2468 (2012).
38. Harvey, M. J., Giupponi, G. & De Fabritiis, G. ACEMD: Accelerating Biomolecular Dynamics in the Microsecond Time Scale. J. Chem. Theory Comput. 5, 1632-1639 (2009).
39. Bowman, G. R., Beauchamp, K. A., Boxer, G. & Pande, V. S. Progress and challenges in the automated construction of Markov state models for full protein systems. J. Chem. Phys. 131, 124101 (2009).
40. Prinz, J.-H. et al. Markov models of molecular kinetics: Generation and validation. J. Chem. Phys. 134, 174105-174105-23 (2011).
41. Doerr, S. & De Fabritiis, G. HTMD - Molecular modelling made simple (2015) Available at: https://www.htmd.org/htmd/index.html (Accessed: 11th January 2016).