Dynamic undocking and the quasi-bound state as tools for drug discovery

Nature Chemistry

Volumn 9, Issue 3, 2017, Pages 201-206

  Ruiz Carmona, Sergio ^a   Schmidtke, Peter ^b   Luque, F Javier ^a   Baker, Lisa ^c   Matassova, Natalia ^c   Davis, Ben ^c   Roughley, Stephen ^c   Murray, James ^c   Hubbard, Rod ^c,d   Barril, Xavier ^a,e  

^a UNIVERSITY OF BARCELONA   (Spain)

^b Discngine   (France)

^c Vernalis PLC   (United Kingdom)

^d UNIVERSITY OF YORK   (United Kingdom)

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

Author keywords

[No Author keywords available]

Indexed keywords

DRUG; HEAT SHOCK PROTEIN 90; LIGAND;

ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; HUMAN; MOLECULAR DOCKING; SYNTHESIS; THERMODYNAMICS;

DRUG DISCOVERY; HSP90 HEAT-SHOCK PROTEINS; HUMANS; LIGANDS; MOLECULAR DOCKING SIMULATION; MOLECULAR STRUCTURE; PHARMACEUTICAL PREPARATIONS; THERMODYNAMICS;

EID: 85013853067     PISSN: 17554330     EISSN: 17554349     Source Type: Journal    
DOI: 10.1038/nchem.2660     Document Type: Article

References (39)

1. Kuhnert, M. et al. Tracing binding modes in hit-to-lead optimization: chameleon-like poses of aspartic protease inhibitors. Angew. Chem. Int. Ed. 54, 2849-2853 (2015).
2. Krohn, A., Redshaw, S., Ritchie, J. C., Graves, B. J. & Hatada, M. H. Novel binding mode of highly potent HIV-proteinase inhibitors incorporating the (R)-hydroxyethylamine isostere. J. Med. Chem. 34, 3340-3342 (1991).
3. Smith, L. J., Van Gunsteren, W. F. & Allison, J. R. Multiple binding modes for palmitate to barley lipid transfer protein facilitated by the presence of proline 12. Protein Sci. 22, 56-64 (2013).
4. Bissantz, C., Kuhn, B. & Stahl, M. A medicinal chemist's guide to molecular interactions. J. Med. Chem. 53, 5061-5084 (2010).
5. Klebe, G. Applying thermodynamic profiling in lead finding and optimization. Nat. Rev. Drug Discov. 14, 95-110 (2015).
6. Ferenczy, G. G. & Keser, G.M. Thermodynamics of fragment binding. J. Chem. Inf. Model. 52, 1039-1045 (2012).
7. Kozakov, D. et al. Ligand deconstruction: why some fragment binding positions are conserved and others are not. Proc. Natl Acad. Sci. USA 112, E2585-E2594 (2015).
8. Schmidtke, P., Luque, F. J., Murray, J. B. & Barril, X. Shielded hydrogen bonds as structural determinants of binding kinetics: Application in drug design. J. Am. Chem. Soc. 133, 18903-18910 (2011).
9. Colizzi, F., Perozzo, R., Scapozza, L., Recanatini, M. & Cavalli, A. Singlemolecule pulling simulations can discern active from inactive enzyme inhibitors. J. Am. Chem. Soc. 132, 7361-7371 (2010).
10. Noble, M. E. M., Endicott, J. A. & Johnson, L. N. Protein kinase inhibitors: insights into drug design from structure. Science 303, 1800-1805 (2004).
11. Anderson, D. R. et al. Benzothiophene inhibitors of MK2. Part 1: structure-activity relationships, assessments of selectivity and cellular potency. Bioorg. Med. Chem. Lett. 19, 4878-4881 (2009).
12. Filippakopoulos, P. & Knapp, S. Targeting bromodomains: epigenetic readers of lysine acetylation. Nat. Rev. Drug Discov. 13, 337-356 (2014).
13. Ember, S. W. J. et al. Acetyl-lysine binding site of bromodomain-containing protein 4 (BRD4) interacts with diverse kinase inhibitors. ACS Chem. Biol. 9, 1160-1171 (2014).
14. Mysinger, M. M., Carchia, M., Irwin, J. J. & Shoichet, B. K. Directory of useful decoys, enhanced (DUD-E): better ligands and decoys for better benchmarking. J. Med. Chem. 55, 6582-6594 (2012).
15. Rask-Andersen, M., Almén, M. S. & Schiöth, H. B. Trends in the exploitation of novel drug targets. Nat. Rev. Drug Discov. 10, 579-590 (2011).
16. Shoichet, B. K. Virtual screening of chemical libraries. Nature 432, 862-865 (2004).
17. Brooijmans, N. & Kuntz, I. D. Molecular recognition and docking algorithms. Annu. Rev. Biophys. Biomol. Struct. 32, 335-373 (2003).
18. Ruiz-Carmona, S. et al. rDock: A fast, versatile and open source program for docking ligands to proteins and nucleic acids. PLoS Comput. Biol. 10, e1003571 (2014).
19. Roughley, S.,Wright, L., Brough, P.,Massey, A. & Hubbard, R. E. Hsp90 inhibitors and drugs from fragment and virtual screening. Top. Curr. Chem. 317, 61-82 (2012).
20. Hajduk, P. J. & Greer, J. A decade of fragment-based drug design: strategic advances and lessons learned. Nat. Rev. Drug Discov. 6, 211-219 (2007).
21. Joseph-McCarthy, D., Campbell, A. J., Kern, G. & Moustakas, D. Fragmentbased lead discovery and design. J. Chem. Inf. Model. 54, 693-704 (2014).
22. Chen, I.-J. & Hubbard, R. E. Lessons for fragment library design: Analysis of output from multiple screening campaigns. J. Comput. Aided Mol. Des. 23, 603-620 (2009).
23. Teotico, D. G. et al. Docking for fragment inhibitors of AmpC -lactamase. Proc. Natl Acad. Sci. USA 106, 7455-7460 (2009).
24. Murray, C.W. et al. Fragment-based drug discovery applied toHsp90. Discovery of two lead series with high ligand efficiency. J. Med. Chem. 53, 5942-5955 (2010).
25. Chipot, C. & Pohorille, A. Free Energy Calculations: Theory and Applications in Chemistry and Biology (Springer, 2007).
26. Alvarez-Garcia, D. & Barril, X. Molecular simulations with solvent competition quantify water displaceability and provide accurate interaction maps of protein binding sites. J. Med. Chem. 57, 8530-8539 (2014).
27. Molecular Operating Environment (MOE), 2014.09 (Chemical Computing Group Inc., 2015).
28. Jakalian, A., Jack, D. B. & Bayly, C. I. Fast, efficient generation of high-quality atomic charges. AM1-BCC model: II. Parameterization and validation. J. Comput. Chem. 23, 1623-1641 (2002).
29. Bayly, C. I., McKay, D. & Truchon, J. F. An Informal AMBER Small Molecule Force Field: parm@Frosst (Computational Chemistry Ltd, 2011).
30. Case, D. A. et al. AMBER 12 (Amber Software, 2012).
31. Ryckaert, J.-P., Ciccotti, G. & Berendsen, H. J. C. Numerical integration of the Cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J. Comput. Phys. 23, 327-341 (1977).
32. Brough, P. A. et al. Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno[2,3-d]pyrimidine inhibitors of the Hsp90 molecular chaperone. J. Med. Chem. 52, 4794-4809 (2009).
33. Baurin, N. et al. Design and characterization of libraries of molecular fragments for use in NMR screening against protein targets. J. Chem. Inf. Comput. Sci. 44, 2157-2166 (2004).
34. Davis, B. in Protein-Ligand Interactions: Methods and Applications, Vol. 1008 (eds Williams, M. A. & Daviter, T.) 389-413 (Springer, 2013).
35. Wright, L. et al. Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms. Chem. Biol. 11, 775-785 (2004).
36. Navaza, J. AMoRe: An automated package for molecular replacement. Acta Crystallogr. A 50, 157-163 (1994).
37. Murshudov, G. N., Vagin, A. A. & Dodson, E. J. Refinement of macromolecular structures by themaximum-likelihoodmethod. Acta Crystallogr.D53, 240-255 (1997).
38. Emsley, P. & Cowtan, K. COOT: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126-2132 (2004).
39. Collaborative Computational Project, Number 4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D 50, 760-763 (1994).