Receptor flexibility in de novo ligand design and docking

Journal of Medicinal Chemistry

Volumn 48, Issue 21, 2005, Pages 6585-6596

  Alberts, Ian L ^a   Todorov, Nikolay P ^a   Dean, Philip M ^a  

^a De Novo Pharmaceuticals Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCHOLINESTERASE; CHOLINESTERASE INHIBITOR; COLLAGENASE; DONEPEZIL; DRUG RECEPTOR; HUPERZINE A; INTERSTITIAL COLLAGENASE; RO 31 4724; RS 104966; TACRINE DERIVATIVE; UNCLASSIFIED DRUG;

ALGORITHM; AMINO ACID SEQUENCE; ARTICLE; BINDING SITE; CALCULATION; DRUG DESIGN; DRUG DETERMINATION; DRUG PROTEIN BINDING; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HUMAN; MATHEMATICAL ANALYSIS; PROTEIN CONFORMATION; SIMULATION;

ACETYLCHOLINESTERASE; AMINO ACIDS; BINDING SITES; CHOLINESTERASE INHIBITORS; COMPUTER SIMULATION; DRUG DESIGN; HUMANS; LIGANDS; MATRIX METALLOPROTEINASE 1; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEASE INHIBITORS; PROTEIN BINDING; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; THERMODYNAMICS;

EID: 27144484954     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050196j     Document Type: Article

References (74)

1. Jorgensen, W. L. The many roles of computation in drug discovery. Science 2004, 303, 1813-1818.
2. Teague, S. J. Implications of protein flexibility for drug discovery. Nat. Rev. Drug Discovery 2003, 2, 527-540.
3. Vieira, E.; Binggeli, A.; Breu, V.; Bur, D.; Fischli, W.; Guller, R.; Hirth G.; Marki, H. P.; Muller, M.; Oefner, C.; Scalone, M.; Stadler, H.; Wilhelm, M.; Wostl, W. Substituted piperidines-highly potent renin inhibitors due to induced fit adaptation of the active site. Bioorg. Med. Chem. Lett. 1999, 9, 1397-1402.
4. Weichsel, A.; Montfrot, W. Ligand-induced distortion of an active site in thymidylate synthase upon binding anticancer drug 1843U89. Nat. Struct. Biol. 1995, 2, 1095-1101.
5. Tong, L.; Pav, S.; Suet, M.; Lamarre, D.; Yoakim, C.; Beaulieu, P.; Anderson, P. Crystal structures of HIV-2 protease in complex with inhibitors containing the hydroxyethylene dipeptide isostere. Structure 1995, 3, 33-40.
6. Najmanovich, R.; Kuttner, J.; Sobolev, V.; Edelman, M. Sidechain flexibility in proteins upon ligand binding. Proteins: Struct., Funct., Genet. 2000, 39, 261-268.
7. Lesk, A. M.; Chothia, C. Elbow motion in immunoglobins involves a molecular ball-and-socket joint. Nature 1988, 335, 188-190.
8. Ewing, T. J. A.; Makino, S.; Skillman, A. G.; Kuntz, I. D. DOCK 4.0; Search strategies for automated molecular docking of flexible molecule databases. J. Comput.-Aided Mol. Des. 2001, 15, 411-428.
9. Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Betlew, R. K.; Olson, A. J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 1998, 19, 1639-1662.
10. Rarey, M.; Kramer, B.; Lengauer, T.; Klebe, G. A fast flexible docking method using an incremental construction algorithm. J. Mol. Biol. 1996, 261, 470-489.
11. Jones, G.; Willet, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 1997, 267, 727-748.
12. Friesner, R. A.; Banks, J. L.; Murphy, R. B.; Halgren, T. A.; Klicic, J. J.; Mainz, D. T.; Repasky, M. P.; Knoll, E. H.; Shelley, M.; Perry, J. K.; Shaw, D. E.; Francis, P.; Shenkin, P. S. Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 2004, 47, 1739-1749.
13. Carlson, H. A.; McCammon, J. A. Accommodating protein flexibility in computational drug design. Mol. Pharmacol. 2000, 57, 213-218.
14. Yoon, S.; Welsh, W. J. Identification of a minimal subset of receptor conformations for improved multiple conformation docking and two-step scoring. J. Chem. Inf. Comput. Sci. 2004, 44, 88-96.
15. Apostolakis, J.; Pluckthun, A.; Caflisch, A. Docking Small Ligands in Flexible Binding-sites. J. Comput. Chem. 1998, 19, 21-37.
16. Cavasotto, C. N.; Abagyan, R. A. Protein flexibility in ligand docking and virtual screening to protein kinases. J. Mol. Biol. 2004, 337, 209-225.
17. Ragno, R.; Frasca, S.; Manetti, F.; Brizzi A.; Massa, S. HIV-Reverse transcriptase inhibition: inclusion of ligand-induced fit by cross-docking studies. J. Med. Chem. 2004.
18. Vigers, G. P. A.; Rizzi, J. P. Multiple active site corrections for docking and virtual screening. J. Med. Chem. 2004, 47, 80-89.
19. Fernandez, M. X.; Kairys, V.; Gilson, M. K. Comparing ligand interactions with multiple receptors via serial docking. J. Chem. Inf. Comput. Sci. 2004, 44, 1961-1970.
20. Knegtel, R. M. A.; Kuntz, I. D.; Oshiro, C. M. Molecular docking to ensembles of protein structures. J. Mol. Biol. 1997, 266, 424-440.
21. Osterberg, F.; Morris, G. M.; Sanner, M. F.; Olsen, A. J.; Goodsell, D. S. Automated docking to multiple targets structures: incorporation of protein mobility and structural water heterogeneity in AutoDock. Proteins: Struct., Funct., Genet. 2002, 46, 34-40.
22. Broughton, H. B. A method for including protein flexibility in protein-ligand docking: improving tools for database mining and virtual screening. J. Mol. Graphics Modell. 2000, 18, 247-257.
23. Totrov, M.; Abagyan, R. Flexible protein-ligand docking by global energy optimization in internal co-ordinates. Proteins: Struct., Funct., Genet. 1997, 29, 215-220.
24. Schnecke, V.; Kuhn, L. A. Virtual screening with solvation and ligand-induced complementarity. Perspect. Drug Discov. 2000, 20, 171-190.
25. Leach, A. R. Ligand docking to proteins with discrete side-chain flexibility. J. Mol. Biol. 1994, 235, 345-356.
26. Frimurer, T. M.; Peters, G. H.; Iversen, L. F.; Andersen, H. S.; Moller, N. P.; Olsen, O. H. Ligand-induced conformational changes: improved predictions of ligand binding conformations and affinities. Biophys. J. 2003, 84, 2273-2281.
27. Taylor, R. D.; Jewsbury, P. J.; Essex, J. W. FDS: flexible ligand and receptor docking with a continuum solvent and soft core energy function. J. Comput. Chem. 2003, 24, 1637-1656.
28. Källblad, P.; Todorov, N. P.; Willems, H. M. G.; Alberts, I. L. Receptor flexibility in the in silico screening of reagents in the S1′ pocket of human collagenase. J. Med. Chem. 2004, 47, 2761-2767.
29. Lill, M. A.; Vedani, A.; Dobler, M. Raptor. Combining dual-shell representation, induced fit simulation, and hydrophobicity scoring in receptor modeling: Application toward the simulation of structurally diverse ligand sets. J. Med. Chem. 2004, 47, 6174-6186.
30. Bouzida, D.; Rejto, P. A.; Arthurs, S.; Colson, A. B.; Freer, S. T.; Gehlhaar, D. K.; Larson, V.; Luty, B. A.; Rose, P. W.; Verkhivker, G. M. Computer simulations of ligand-protein binding with ensembles of protein conformations: A Monte Carlo study of HIV-1 protease binding energy landscapes. Int. J. Quantum Chem. 1999, 72, 73-84.
31. Murray, C. W.; Baxter, C. A.; Frenkel, A. D. The sensitivity of the results of molecular docking to induced fit effects: application to thrombin, thermolysin and neuraminidase. J. Comput.-Aided Mol. Des. 1999, 13, 547-562.
32. Carlson, H. A. Protein flexibility is an important component of structure-based drug discovery. Curr. Pharm. Dis. 2002, 8, 1571-1578.
33. st century: inhibitors targeting conformational ensembles. J. Med. Chem. 2002, 45, 541-558.
34. Zhu, J.; Fan, H.; Liu, H.; Shi, Y. Structure-based ligand design for flexible proteins: Application of new F-DycoBlock. J. Comput.-Aided Mol. Des. 2001, 15, 979-996.
35. Böhm, H.-J. The computer program LUDI: a new method for the de novo design of enzyme inhibitors. J. Comput.-Aided Mol. Des. 1992, 6, 61-78.
36. Eisen, M. B.; Wiley, D. C.; Karplus, M.; Hubbard, R. E. HOOK: a program for finding novel molecular architectures that satisfy the chemical and steric requirements of a macromolecule binding-site. Proteins: Struct., Funct., Genet. 1994, 19, 199-221.
37. Gillet, V.; Johnson, A. P.; Mata, P.; Sike, S.; Williams, P. SPROUT: a program for structure generation. J. Comput.-Aided. Mol. Des. 1994, 7, 127-153.
38. Stahl, M.; Todorov, N. P.; James, T.; Mauser, H.; Boehm, H. J.; Dean, P. M. A validation study of the practical use of automated de novo design. J. Comput.-Aided Mol. Des. 2002, 16, 459-478.
39. Chung, S. Y.; Subbiah, S. How similar must a template protein be for homology modelling by side-chain packing methods? In Pacific Symposium On Biocomputing; Hunter, L., Klein, T. E., Eds.; World Scientific: Hawaii, 1996; pp 126-141.
40. Najmanovich, R.; Kuttner, J.; Sobolev, V.; Edelman, M. Side-chain flexibility in proteins upon ligand binding. Proteins: Struct, Funct., Genet. 2000, 39, 261-268.
41. Ponder, J. W.; Richards, F. M. Tertiary templates for proteins-use of packing criteria in the enumeration of allowed sequences for different structural classes. J. Mol. Biol. 1987, 193, 775-791.
42. Dunbrack, R. L.; Karplus, M. Back-bone-dependent rotamer library for proteins-application to side-chain prediction. J. Mol. Biol. 1993, 230, 543-574.
43. Dunbrack, R. L.; Cohen, F. E. Bayesian statistical analysis of protein side-chain rotamer preferences. Protein Sci. 1997, 6, 1661-1681.
44. Xiang, Z.; Honig, B. Extending the Accuracy Limits of Prediction for Side-chain Conformations. J. Mol. Biol. 2001, 311, 421-430.
45. Lovell, S. C.; Word, J. M.; Richardson, J. S.; Richardson D. C. The penultimate rotamer library. Proteins: Struct., Funct., Genet. 2000, 40, 389-408.
46. Sali, A.; Blundell, T. L. Comparative protein modeling by satisfaction of spatial constraints. J. Mol. Biol. 1993, 234, 779-815.
47. Bower, M.; Cohen, F.; Dunbrack, R. J. Prediction of protein side-chain rotamers from a back-bone-dependent rotamer library: a new homology modeling tool. J. Mol. Biol. 1997, 267, 1268-1282.
48. Dahiyat, B. I.; Mayo, S. L. De novo protein design: fully automated sequence selection. Science 1997, 278, 82-87.
49. Wernisch, L.; Hery, S.; Wodak, S. J. Automatic protein design with all atom force-fields by exact and heuristic optimization. J. Mol. Biol. 2000, 301, 713-736.
50. Desjarlais, J. R.; Handel, T. M. Side-chain and back-bone flexibility in protein core design. J. Mol. Biol. 1999, 290, 305-318.
51. Lee, C.; Subbiah, S. Prediction of protein side-chain conformation by packing optimization. J. Mol. Biol. 1991, 217, 272-288.
52. Desmet, J.; De Maeyer, M.; Hazes, B.; Lasters, I. The dead-end elimination theorem and its use in protein side-chain positioning. Nature 1992, 356, 539-542.
53. Lasters, I.; Desmet, J. The fuzzy-end elimination theorem: correctly implementing the side-chain placement algorithm based on the dead-end elimination theorem. Protein Eng. 1993, 6, 717-722.
54. Keller, D.; Shibata, M.; Markus, E.; Ornstein, R.; Rein, R. Finding the global minimum: a fuzzy end elimination implementation. Protein Eng. 1995, 8, 893-904.
55. Todorov, N. P.; Dean, P. M. An evaluation of a method for controlling molecular scaffold diversity in de novo ligand design. J. Comput.-Aided Mol. Des. 1997, 11, 175-192.
56. Todorov, N. P.; Dean, P. M. Computational Ligand Design by Free Energy Minimization. In Biological Physics; Frauenfelder, H., Hummer, G., Garcia, R., Eds.; American Institute of Physics: New York, 1999.
57. Kryger, G.; Silman, I.; Sussman, J. L. Structure of acetylcholinesterase complexed with E2020 (Donepezil): implications for the design of new anti-Alzheimer drugs. Structure 1999, 7, 297-307.
58. Raves, M. L.; Harel, M.; Pang, Y.-P.; Silman, I.; Kozikowski, A. P.; Sussman, J. L. Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A. Nat. Struct. Biol. 1997, 4, 57-63.
59. Harel, M.; Kryger, G.; Rosenberry, T. R.; Mallender, W. D.; Lewis, T.; Fletcher, R. J.; Guss, J. M.; Silman, I.; Sussman, J. L. Three-dimensionsal structures of Drosophila melanogaster acetylcholinesterase and of its complexes with two potent inhibitors. Protein Sci. 2000, 9, 1063-1072.
60. Coussence, L. M.; Fingleton, B.; Matrisian, L. M. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 2002, 295, 2387-2392.
61. Cleutjens, J. P. The role of matrix metalloproteinases in heart disease. Cardiovasc. Res. 1996, 30, 816-821.
62. Beckett, R. P.; Whittaker, M. Matrix metalloproteinase inhibitors. Expert Opin. Ther. Pat. 1998, 8, 259-282.
63. Babine, R. E.; Bender, S. L. Molecular recognition of protein-ligand complexes: Applications to drug design. Chem. Rev. 1997, 97, 1359-1472.
64. Moy, F. J.; Chanda, P. K.; Chen, J. M.; Cosmi, S.; Edris, W.; Skotnicki, J. W.; Powers, R. Solution structure of the catalytic fragment of human fibroblast collagenase complexed with a sulphonamide derivative of a hydroxamic acid compound. Biochemistry 1999, 38, 7085-7096.
65. Botos, I.; Scapozza, L.; Zhang, D.; Liotta, L. A.; Meyer, E. F. Batimastat, a potent matrix metalloproteinase inhibitor, exhibits an unexpected mode of binding. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 2749-2754.
66. Lovejoy, B.; Welsh, A. R.; Carr, S.; Luong, C.; Broka, C.; Hendricks, R. T. Campbell, J. A.; Walker, K. A. M. Martin, R.; van Wart, H.; et al. Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors. Nat. Struct. Biol. 1999, 6, 217-221.
67. Maple, J. R.; Dinur, U.; Hegler, E. T. Derivation of force fields for molecular mechanics and dynamics from ab initio energy surfaces. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 5350-5354.
68. Bondi, A. van der Waals volumes and radii. J. Phys. Chem. 1968, 68, 441-451.
69. Stahl, M.; Rarey, M. Detailed Analysis of Scoring Functions for Virtual Screening. J. Med. Chem. 2001, 44, 1035-1042.
70. Lewell, X. Q.; Judd, D. B.; Watson, S. P.; Hann, M. M. RECAP: retrosynthetic combinatorial analysis procedure: a powerful new technique for identifying privileged molecular fragments with useful applications in combinatorial chemistry. J. Chem. Inf. Comput. Sci. 1998, 38, 511-522.
71. Erickson, J. A.; Jalaie, M.; Robertson, D. H.; Lewis, R. A.; Vieth, M. Lessons in molecular recognition: The effects of ligand and protein flexibility on molecular docking accuracy. J. Med. Chem. 2004, 47, 45-55.
72. Källblad, P.; Dean, P. M. Efficient sampling of local side-chain flexibility. J. Mol. Biol. 2003, 326, 1651-1665.
73. Källblad, P.; Mancera, R. L.; Todorov, N. Assessment of Ligand Binding Modes in Protein-Ligand Docking. J. Med. Chem. 2004, 47, 3334-3337.
74. Borkakoti, N.; Winkler, F. K.; Williams, D. H.; Darcy, A.; Broadhurst, M. J.; Brown, P. A.; Johnson, W. H.; Murray, E. J. Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor. Nat. Struct. Biol. 1994, 1, 106-110.