Torsion angle preferences in druglike chemical space: A comprehensive guide

Journal of Medicinal Chemistry

Volumn 56, Issue 5, 2013, Pages 2016-2028

  Schärfer, Christin ^a   Schulz Gasch, Tanja ^b   Ehrlich, Hans Christian ^a   Guba, Wolfgang ^b   Rarey, Matthias ^a   Stahl, Martin ^b  

^a UNIVERSITY OF HAMBURG   (Germany)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; COMPUTER INTERFACE; COMPUTER PROGRAM; CRYSTAL STRUCTURE; DRUG CONFORMATION; HISTOGRAM; MECHANICAL TORSION; MOLECULAR LIBRARY; STRUCTURE ANALYSIS;

DATABASES, FACTUAL; DRUG DESIGN; DRUG DISCOVERY; MODELS, MOLECULAR; MOLECULAR CONFORMATION; ROTATION; SOFTWARE; TORSION, MECHANICAL;

EID: 84875132987     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm3016816     Document Type: Article

References (55)

1. Hawkins, P. C. D.; Skillman, A. G.; Warren, G. L.; Ellingson, B. A.; Stahl, M. T. Conformer Generation with OMEGA: Algorithm and Validation Using High Quality Structures from the Protein Databank and Cambridge Structural Database J. Chem. Inf. Model. 2010, 50, 572-584
2. Watts, K. S.; Dalal, P.; Murphy, R. B.; Sherman, W.; Friesner, R. A.; Shelley, J. C. ConfGen: A Conformational Search Method for Efficient Generation of Bioactive Conformers J.Chem. Inf. Model. 2010, 50, 534-546
3. MacroModel, version 9.6; Schrödinger, LLC: New York, NY, 2012; http://www.schrodinger.com/productpage/14/11/ (accessed Oct 18, 2012).
4. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. MacroModel-An Integrated Software System for Modeling Organic and Bioorganic Molecules Using Molecular Mechanics J. Comput. Chem. 1990, 11, 440-467
5. Chang, G.; Guida, W. C.; Still, W. C. An Internal-Coordinate Monte Carlo Method for Searching Conformational Space J. Am. Chem. Soc. 1989, 111, 4379-4386
6. 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
7. Crippen, G. M. Note Rapid Calculation of Coordinates from Distance Matrices J. Comput. Phys. 1978, 26, 449-452
8. Izrailev, S.; Zhu, F.; Agrafiotis, D. K. A Distance Geometry Heuristic for Expanding the Range of Geometries Sampled during Conformational Search J. Comput. Chem. 2006, 27, 1962-1969 (Pubitemid 44787014)
9. Rusinko, A., III; Sheridan, R. P.; Nilakantan, R. Using CONCORD To Construct a Large Database of Three-Dimensional Coordinates from Connection Tables J. Chem. Inf. Comput. Sci. 1989, 29, 251-255 (Pubitemid 20644301)
10. Gasteiger, J.; Rudolph, C.; Sadowski, J. Automatic Generation of 3D-Atomic Coordinates for Organic Molecules Tetrahedron Comput. Methodol. 1990, 3, 537-547
11. Kolossváry, I.; Guida, W. C. Low Mode Search. An Efficient, Automated Computational Method for Conformational Analysis: Application to Cyclic and Acyclic Alkanes and Cyclic Peptides J. Am. Chem. Soc. 1996, 118, 5011-5019 (Pubitemid 26200976)
12. Kolossváry, I.; Guida, W. C. Low-Mode Conformational Search Elucidated: Application to C39H80 and Flexible Docking of 9-Deazaguanine Inhibitors into PNP J. Comput. Chem. 1999, 20, 1671-1684 (Pubitemid 129653223)
13. Rarey, M.; Kramer, B.; Lengauer, T. Time-Efficient Docking of Flexible Ligands into Active Sites of Proteins Proc. Int. Conf. Intell. Syst. Mol. Biol. 1995, 3, 300-308
14. 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 (Pubitemid 38380917)
15. Halgren, T. A.; Murphy, R. B.; Friesner, R. A.; Beard, H. S.; Frye, L. L.; Pollard, W. T.; Banks, J. L. Glide: A New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening J. Med. Chem. 2004, 47, 1750-1759 (Pubitemid 38380918)
16. Dixon, S. L.; Smondyrev, A. M.; Knoll, E. H.; Rao, S. N. PHASE: A New Engine for Pharmacophore Perception, 3D QSAR Model Development, and 3D Database Screening: 1. Methodology and Preliminary Results J. Comput.-Aided Mol. Des. 2006, 20, 647-671 (Pubitemid 46023928)
17. Rush, T. S.; Grant, J. A.; Mosyak, L.; Nicholls, A. A Shape-Based 3-D Scaffold Hopping Method and Its Application to a Bacterial Protein-Protein Interaction J. Med. Chem. 2005, 48, 1489-1495 (Pubitemid 40364556)
18. Grant, J. A.; Gallardo, M. A.; Pickup, B. T. A fast Method of Molecular Shape Comparison: A Simple Application of a Gaussian Description of Molecular Shape J. Comput. Chem. 1998, 17, 1653-1666 (Pubitemid 126535414)
19. Allen, F. H. The Cambridge Structural Database: A Quarter of a Million Crystal Structures and Rising Acta Crystallogr. 2002, B58, 380-388 (Pubitemid 135702674)
20. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank Nucleic Acids Res. 2000, 28, 235-242 (Pubitemid 30047768)
21. Mogul-A Knowledge Base of Molecular Geometry, version 3.0; The Cambridge Crystallographic Data Centre: Cambridge, U.K.; http://www.ccdc.cam.ac.uk/ products/csd-system/mogul/ (accessed Oct 15, 2012).
22. ConQuest-The Interface for the CSD System, version 1.14; The Cambridge Crystallographic Data Centre: Cambridge, U.K.; http://www.ccdc.cam.ac.uk/ products/csd-system/conquest/ (accessed Oct 15, 2012).
23. Klebe, G.; Mietzner, T. A Fast and Efficient Method To Generate Biologically Relevant Conformations J. Comput.-Aided Mol. Des. 1994, 8, 583-606
24. Sadowski, J.; Boström, J. MIMUMBA Revisited: Torsion Angle Rules for Conformer Generation Derived from X-ray Structures J. Chem. Inf. Model. 2006, 46, 2305-2309 (Pubitemid 46008104)
25. Brameld, K. A.; Kuhn, B.; Reuter, D. C.; Stahl, M. Small Molecule Conformational Preferences Derived from Crystal Structure Data. A Medicinal Chemistry Focused Analysis J. Chem. Inf. Model. 2008, 48, 1-24 (Pubitemid 351271046)
26. Bissantz, C.; Kuhn, B.; Stahl, M. A Medicinal Chemist's Guide to Molecular Interactions J. Med. Chem. 2010, 53, 5061-5084
27. Hardegger, L. A.; Kuhn, B.; Spinnler, B.; Anselm, L.; Ecabert, R.; Stihle, M.; Gsell, B.; Thoma, R.; Diez, J.; Benz, J.; Plancher, J.-M.; Hartmann, G.; Banner, D. W.; Haap, W.; Diederich, F. Systematic Investigation of Halogen Bonding in Protein-Ligand Interactions Angew. Chem., Int. Ed. 2011, 50, 314-318
28. Kuhn, B.; Fuchs, J. E.; Reutlinger, M.; Stahl, M.; Taylor, N. R. Rationalizing Tight Ligand Binding through Cooperative Interaction Networks J. Chem. Inf. Model. 2011, 51, 3180-3198
29. Kuhn, B.; Mohr, P.; Stahl, M. Intramolecular Hydrogen Bonding in Medicinal Chemistry J. Med. Chem. 2010, 53, 2601-2611
30. Czekaj, M.; Klein, S. I.; Guertin, K. R.; Gardner, C. J.; Zulli, A. L.; Pauls, H. W.; Spada, A. P.; Cheney, D. L.; Brown, K. D.; Colussi, D. J.; Chu, V.; Leadley, R. J.; Dunwiddie, C. T. Optimization of the beta-Aminoester Class of Factor Xa Inhibitors. Part 1: P4 and Side-Chain Modifications for Improved in Vitro Potency Bioorg. Med. Chem. Lett. 2002, 12, 1667-1670 (Pubitemid 34569267)
31. Guertin, K. R.; Gardner, C. J.; Klein, S. I.; Zulli, A. L.; Czekaj, M.; Gong, Y.; Spada, A. P.; Cheney, D. L.; Maignan, S.; Guilloteau, J.-P.; Brown, K. D.; Colussi, D. J.; Chu, V.; Heran, C. L.; Morgan, S. R.; Bentley, R. G.; Dunwiddie, C. T.; Leadley, R. J.; Pauls, H. W. Optimization of the beta-Aminoester Class of Factor Xa Inhibitors. Part 2: Identification of FXV673 as a Potent and Selective Inhibitor with Excellent in Vivo Anticoagulant Activity Bioorg. Med. Chem. Lett. 2002, 12, 1671-1674 (Pubitemid 34569268)
32. Leung, C. S.; Leung, S. S. F.; Tirado-Rives, J.; Jorgensen, W. L. Methyl Effects on Protein-Ligand Binding J. Med. Chem. 2012, 55, 4489-4500
33. Chein, R.-J.; Corey, E. J. Strong Conformational Preferences of Heteroaromatic Ethers and Electron Pair Repulsion Org. Lett. 2010, 12, 132-135
34. Cruz-Cabeza, A. J.; Liebeschuetz, J. W.; Allen, F. H. Systematic Conformational Bias in Small-Molecule Crystal Structures Is Rare and Explicable CrystEngComm 2012, 14, 6797-6811
35. Pascal, R. A.; Wang, C. M.; Wang, G. C.; Koplitz, L. V. Ideal Molecular Conformation versus Crystal Site Symmetry Cryst. Growth Des. 2012, 12, 4367-4376
36. Warren, G. L.; Do, T. D.; Kelley, B. P.; Nicholls, A.; Warren, S. D. Essential Considerations for Using Protein-Ligand Structures in Drug Discovery Drug Discovery Today 2012, 17, 1270-1281
37. Kiefer, J. R.; Pawlitz, J. L.; Moreland, K. T.; Stegeman, R. A.; Hood, W. F.; Gierse, J. K.; Stevens, A. M.; Goodwin, D. C.; Rowlinson, S. W.; Marnett, L. J.; Stallings, W. C.; Kurumbail, R. G. Structural Insights into the Stereochemistry of the Cyclooxygenase Reaction Nature 2000, 405, 97-101 (Pubitemid 30321823)
38. Ke, W.; Bethel, C. R.; Papp-Wallace, K. M.; Pagadala, S. R. R.; Nottingham, M.; Fernandez, D.; Buynak, J. D.; Bonomo, R. A.; van den Akker, F. Crystal Structures of KPC-2 beta-Lactamase in Complex with 3-Nitrophenyl Boronic Acid and the Penam Sulfone PSR-3-226 Antimicrob. Agents Chemother. 2012, 56, 2713-2718
39. Edwards, T. E.; Davies, D. R.; Hartley, R.; Zeller, W. Crystal Structure of 2 C -Methyl- d -erythritol 2,4-Cyclodiphosphate Synthase from Burkholderia pseudomallei in Complex with a Fragment-Nucleoside Fusion D000161829. http://www.rcsb.org/pdb/explore/explore.do?structureId=3ke1 (accessed Dec 4, 2012).
40. Pireddu, R.; Forinash, K. D.; Sun, N. N.; Martin, M. P.; Sung, S.-S.; Alexander, B.; Zhu, J.-Y.; Guida, W. C.; Schonbrunn, E.; Sebti, S. M.; Lawrence, N. J. Pyridylthiazole-Based Ureas as Inhibitors of Rho Associated Protein Kinases (ROCK1 and 2) Med. Chem. Commun. 2012, 3, 699-709
41. Xu, H. E.; Lambert, M. H.; Montana, V. G.; Parks, D. J.; Blanchard, S. G.; Brown, P. J.; Sternbach, D. D.; Lehmann, J. M.; Wisely, G. B.; Willson, T. M.; Kliewer, S. A.; Milburn, M. V. Molecular Recognition of Fatty Acids by Peroxisome Proliferator-Activated Receptors Mol. Cell 1999, 3, 397-403 (Pubitemid 29290680)
42. Daylight Theory Manual: SMARTS-A Language for Describing Molecular Patterns; Daylight Chemical Information Systems: Laguna Niguel, CA; http://www.daylight.com/dayhtml/doc/theory/theory.smarts.html (accessed Nov 1, 2012).
43. SMARTS Pattern Matching; OpenEye Scientific Software: Cambridge, MA; http://www.eyesopen.com/docs/toolkits/current/html/OEChem-TK-python/SMARTS.html (accessed Aug 06, 2012).
44. SMARTS; Open Babel; http://openbabel.org/wiki/SMARTS (accessed Aug 06, 2012).
45. Ray, L. C.; Kirsch, R. A. Finding Chemical Records by Digital Computers Science 1957, 126, 814-819
46. Sussenguth, E. H. A Graph-Theoretic Algorithm for Matching Chemical Structures J. Chem. Doc. 1965, 5, 36-43
47. Ullmann, J. R. An Algorithm for Subgraph Isomorphism J. Assoc. Comput. Mach. 1976, 23, 31-42
48. Cordella, L.; Foggia, P.; Sansone, C.; Vento, M. Performance Evaluation of the VF Graph Matching Algorithm Image Anal. Process. 1999, 1172-1177
49. Cordella, L. P.; Foggia, P.; Sansone, C.; Vento, M. A (Sub)Graph Isomorphism Algorithm for Matching Large Graphs IEEE Trans. Pattern Anal. Mach. Intell. 2004, 26, 1367-1372
50. Ehrlich, H.-C.; Rarey, M. Systematic Benchmark of Substructure Search in Molecular Graphs. From Ullmann to VF2 J. Cheminf. 2012, 41, 13
51. Schomburg, K.; Ehrlich, H.-C.; Stierand, K.; Rarey, M. From Structure Diagrams to Visual Chemical Patterns J. Chem. Inf. Model. 2010, 50, 1529-1535
52. Urbaczek, S.; Kolodzik, A.; Fischer, J. R.; Lippert, T.; Heuser, S.; Groth, I.; Schulz-Gasch, T.; Rarey, M. NAOMI: On the Almost Trivial Task of Reading Molecules from Different File Formats J. Chem. Inf. Model. 2011, 51, 3199-3207
53. Proasis2; Desert Scientific Software: Norwest NSW, Australia; http://www.desertsci.com/ (accessed Oct 16, 2012).
54. Cottrell, S. J.; Olsson, T.; Taylor, R.; Cole, J. C. Validating and Understanding Ring Conformations Using Small Molecule Crystallographic Data J. Chem. Inf. Model. 2012, 52, 956-962
55. Schulz-Gasch, T.; Schärfer, C.; Guba, W.; Rarey, M. TFD: Torsion Fingerprints as a New Measure To Compare Small Molecule Conformations J. Chem. Inf. Model. 2012, 52, 1499-1512