Conformational sampling of druglike molecules with MOE and catalyst: Implications for pharmacophore modeling and virtual screening

Journal of Chemical Information and Modeling

Volumn 48, Issue 9, 2008, Pages 1773-1791

  Chen, I Jen ^a   Foloppe, Nicolas ^a  

^a Vernalis PLC   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CATALYSTS; CELL PROLIFERATION; IMPORTANCE SAMPLING; MOLECULES; PHARMACODYNAMICS; SOFTWARE TESTING; STOCHASTIC SYSTEMS;

BIOACTIVE CONFORMATION; BIOACTIVE CONFORMERS; CONFORMATIONAL ANALYSIS; CONFORMATIONAL SAMPLINGS; CONFORMATIONAL SPACE; GLOBAL ENERGY MINIMA; PHARMACEUTICAL RESEARCH; PHARMACOPHORE MODELING;

CONFORMATIONS;

LIGAND;

ARTICLE; CHEMICAL MODEL; COMPARATIVE STUDY; COMPUTER PROGRAM; COMPUTER SIMULATION; CONFORMATION; DRUG DESIGN; THERMODYNAMICS; THREE DIMENSIONAL IMAGING; TIME;

COMPUTER SIMULATION; DRUG DESIGN; IMAGING, THREE-DIMENSIONAL; LIGANDS; MODELS, CHEMICAL; MOLECULAR CONFORMATION; SOFTWARE; THERMODYNAMICS; TIME FACTORS;

EID: 54249090791     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci800130k     Document Type: Article

References (51)

1. Jones, G.; Willett, P.; Glen, R. C. A genetic algorithm for flexible molecular overlay and pharmacophore elucidation. J. Comput.-Aided Mol. Des. 1995, 9, 532-549.
2. Lemmen, C.; Lengauer, T.; Klebe, G. FlexS: A Method for Fast Flexible Ligand Superposition. J. Med Chem. 1998, 41, 4502-4520.
3. Labute, P.; Williams, C. Flexible Alignment of Small Molecules. J. Med. Chem. 2001, 44, 1483-1490.
4. Green, J.; Kahn, S.; Savoj, H.; Sprague, P.; Teig, S. Chemical Function Queries for 3D Database Search. J. Chem. Inf. Comput. Sci. 1994, 34, 1297-1308.
5. Cramer, R. D., III; Patterson, D. E.; Bunce, J. D. Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J. Am. Chem. Soc. 1988, 110, 5959-5967.
6. Howard, A. E.; Kollman, P. A. An Analysis of Current Methodologies for Conformational Searching of Complex Molecules. J. Med. Chem. 1988, 31, 1669-1675.
7. Leach, A. R. A Survey of Methods for Searching the Conformational Space of Small and Medium-Sized Molecules. In Reviews in Computational Chemistry; Lipkowitz, K. B., Boyd, D. B., Eds.; VCH Publishers: New York, 1991; pp 1-55.
8. Rusinko, A., III; Sheridan, R. P.; Nilakantan, R.; Harald, K. S.; Bauman, N.; et al. Using CONCORD To Construct a Large Database of Three-Dimensional Coordinates from Connection Tables. J. Chem. Inf. Comput. Sci. 1989, 29, 251-255.
9. Gasteiger, J.; Rudolph, C.; Sadowski, J. Automatic Generation of 3D-Atomic Coordinates for Organic Molecules. Tetrahedron Comput. Methodol. 1990, 3, 537-547.
10. Crippen, G. M. Rapid Calculation of Coordinates from Distance Matrices. J. Comput. Phys. 1978, 26, 449-452.
11. Bruccoleri, R.; Karplus, M. Prediction of the Folding of Short Polypeptide Segments by Uniform Conformational Sampling. Biopolymers 1987, 26, 137-168.
12. Ferguson, D. M.; Raber, D. J. A New Approach to Probing Conformational Space with Molecular Mechanics: Random Incremental Pulse Search. J. Am. Chem. Soc. 1989, 111, 4371-4378.
13. Klebe, G.; Mietmer, T. A fast and efficient method to generate biologically relevant conformations. J. Comput.-Aided Mol. Des. 1994, 8, 583-606.
14. Hurst, T. Flexible 3D Searching: The Directed Tweak Technique. J. Chem. Inf. Comput. Sci. 1994, 34, 190-196.
15. Smellie, A.; Teig, S. L.; Towbin, P. Poling: Promoting Conformational Variation. J. Comput. Chem. 1995, 16, 171-187.
16. Baxter, C. A.; Murray, C. W.; Clark, D. E.; Westhead, D. R.; Eldridge, M. D. Flexible docking using Tabu search and an empirical estimate of binding affinity. Proteins: Struct., Funct., Genet. 1998, 33, 367-382.
17. Chang, G.; Guida, W. C.; Still, W. C. An Internal Coordinate Monte Carlo Method for Searching Conformation Space. J. Am. Chem. Soc. 1989, 111, 4379-4386.
18. Foloppe, N.; Nilsson, L. Toward a Full Characterization of Nucleic Acid Components in Aqueous Solution: Simulations of Nucleosides. J. Phys. Chem. B 2005, 109, 9119-9131.
19. Clark, M.; Cramer, R D., III; Van Opdenbosch, N. Validation of the general purpose tripos 5.2 force field. J. Comput Chem. 1989, 10, 982-1012.
20. Momany, F. A.; Rone, R. Validation of the General Purpose QUANTA 3.2/CHARMm Force Field. J. Comput. Chem. 1992, 13, 888-900.
21. Halgren, T. Merck Molecular Force Field. I. Basis, Form, Scope, Parameterization, and Performance of MMFF94. J. Comput. Chem. 1996, 17, 490-519.
22. Jorgensen, W. L.; Maxwell, D. S.; Tirado-Rives, J. Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids. J. Am. Chem. Soc. 1996, 118, 11225-11236.
23. Wang, J.; Wolf, R. M.; Caldwell, J. W.; Kollman, P. A.; Case, D. A. Development and testing of a general Amber force field. J. Comput. Chem. 2004, 25, 1157-1174.
24. Oellien, F.; Cramer, J.; Beyer, C.; Ihlenfeldt, W.-D.; Selzer, P. M. The Impact of Tautomer Forms on Pharmacophore-Based Virtual Screening. J. Chem. Inf. Model 2006, 46, 2342-2354.
25. Catalyst, Accelrys, Inc.: 10188 Telesis Court, Suite 100, San Diego, CA 92121, U.S.A. http://www.accelrys.com(Accessed June 11, 2008).
26. Omega; OpenEye Scientific Software: 9 Bisbee Court, Suite D, Santa Fe, NM 87508. http://www.eyesopen.com (accessed June 11, 2008).
27. Phase; Schrodingen 120 West 45th Street, 29th Floor, New York, NY 10036-4041. http://www.schrodinger.com (accessed June 11, 2008).
28. MOE; Chemical Computing Group: 1010 Sherbrooke St. W, Suite 910, Montieal, Quebec, Canada H3A 2R7. http://www.chemcomp.com (accessed June 11, 2008).
29. Borodina, Y.; Bolton, E.; Fontaine, F.; Bryant, S. H. Assessment of Conformational Ensemble Sizes Necessary for Specific Resolutions of Coverage of Conformational Space. J. Chem. Inf. Model 2007, 47, 1428-1437.
30. Bostrom, J.; Greenwood, J. R.; Gottfries, J. Assessing the performance of OMEGA with respect to retrieving bioactive conformations. J. Mol. Graphics Modell. 2002, 21, 449-462.
31. Bostrom, J. Reproducing the conformations of protein-bound ligands: A critical evaluation of several popular conformational searching tools. J. Comput-Aided Mol. Des. 2001, 15, 1137-1152.
32. Kirchmair, J.; Laggner, C.; Wolber, G.; Langer, T. Comparative Analysis of Protein-Bound Ligand Conformations with Respect to Catalyst's Conformational Space Subsampling Algorithms. J. Chem. Inf. Model 2005, 45, 422-430.
33. Kirchmair, J.; Wolber, G.; Laggner, C.; Langer, T. Comparative Performance Assessment of the Conformational Model Generators Omega and Catalyst: A Large-Scale Survey on the Retrieval of Protein-Bound Ligand Conformations. J. Chem. Inf. Model. 2006, 46, 1848-1861.
34. Nicklaus, M. C.; Shaomeng, W.; Driscoll, J. S.; Milne, W. A. Conformational Changes of Small Molecules Binding to Proteins. Biorg. Med. Chem. 1995, 3, 411-428.
35. Perola, E.; Charifson, P. S. Conformational Analysis of Drug-Like Molecules Bound to Proteins: An Extensive Study of Ligand Reorganization upon Binding. J. Med. Chem. 2004, 47, 2499-2510.
36. Vieth, M.; Hirst, J. D.; BrooksIII, C. L. Do active conformations of small ligands correspond to low free-energy solution structures. J. Comput-Aided Mol. Des. 1998, 12, 563-572.
37. Bostrom, J.; Norrby, P. O.; Liljefors, T. Conformational energy penalties of protein-bound ligands. J. Comput-Aided Mol. Des. 1998, 12, 383-396.
38. Hartshorn, M. J.; Verdonk, M. L.; Chessari, G.; Brewerton, S. C.; Mooij, W. T. M.; et al. Diverse, High-Quality Test Set for the Validation of Protein-Ligand Docking Performance. J. Med. Chem. 2007, 50, 126-141.
39. Agrafions, D. K.; Gibbs, A. C.; Zhu, F.; Izrailev, S.; Martin, E. Conformational Sampling of Bioactive Molecules: A Comparative Study. J. Chem. Inf. Model. 2007, 47, 1067-1086.
40. Diller, D. J.; Merz, K. M. Can we separate active from inactive conformations. J. Comput.-Aided Mol. Des. 2002, 16, 105-112.
41. Gunther, S.; Senger, C.; Michalsky, E.; Goede, A.; Preissner, R. Representation of target-bound drugs by computed conformers: implications for conformational libraries. BMC Bioinformatics 2006, 7, 293-304.
42. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; et al. The Protein Data Bank. Nucleic Acids Res. 2000, 28, 235-242.
43. McGregor, M. J.; Pallai, P. V. Clustering of Large Databases of Compounds: Using the MDL "Keys" as Structural Descriptors. J. Chem. Inf. Comput. Sci. 1997, 37, 443-448.
44. Onufriev, A.; Bashford, D.; Case, D. A. Modification of the Generalized Born Model Suitable for Macromolecules. J. Phys. Chem. B 2000, 104, 3712-3720.
45. Smellie, A.; Kahn, S. D.; Teig, S. L. Analysis of Conformational Coverage. 1. Validation and Estimation of Coverage. J. Chem. Inf. Comput. Sci. 1995, 35, 285-294.
46. Ming-Hong, H.; Haq, O.; Muegge, I. Torsion Angle Preference and Energetics of Small-Molecule Ligands Bound to Proteins. J. Chem. Inf. Model. 2007, 47, 2242-2252.
47. Oprea, T. I.; Davis, A. M.; Teague, S. J.; Leeson, P. D. Is There a Difference between Leads and Drugs? A historical Perspective. J. Chem. Inf. Comput. Sci. 2001, 41, 1308-1315.
48. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Delivery Rev. 1997, 23, 3-25.
49. Hann, M. M.; Leach, A. R.; Harper, G. Molecular Complexity and Its Impact on the Probability of Finding Leads for Drug Discovery. J. Chem. Inf. Comput. Sci. 2001, 41, 856-864.
50. Ferguson, D. M.; Glauser, W. A.; Raber, D. J. Molecular mechanics conformational analysis of cyclononane using the RIPS method and comparison with quantum-mechanical calculations. J. Comput. Chem. 1989, 10, 903-910.
51. Saunders, M.; Houk, K. N.; Wu, Y. D.; Still, W. C.; Lipton, M.; et al. Conformations of Cycloheptadecane. A Comparison of Methods for Conformational Searching. J. Am. Chem. Soc. 1990, 112, 1419-1427.