GALAHAD: 1. Pharmacophore identification by hypermolecular alignment of ligands in 3D

Journal of Computer-Aided Molecular Design

Volumn 20, Issue 9, 2006, Pages 567-587

  Richmond, Nicola J ^a,c   Abrams, Charlene A ^b   Wolohan, Philippa R N ^b   Abrahamian, Edmond ^b   Willett, Peter ^a   Clark, Robert D ^b  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

^b TRIPOS INC   (United States)

^c GLAXOSMITHKLINE   (United Kingdom)

Author keywords

GALAHAD; Hypermolecule; Hyperstructure; Molecular alignment; Pharmacophore; Pharmacostere; Shape similarity

Indexed keywords

CRYSTAL STRUCTURE; HYDROGEN BONDS; ITERATIVE METHODS; LIGANDS; MOLECULES; PHARMACODYNAMICS;

DRUG DEVELOPMENT; DRUG DISCOVERY; GALAHADS; HYPERMOLECULE; HYPERSTRUCTURES; MULTIPLE LIGANDS; PARTIAL MATCHES; PHARMACOPHORES; PHARMACOSTERE; SHAPE SIMILARITY;

ALIGNMENT;

5 DEAZAFOLATE; AMIDE; CYCLIN DEPENDENT KINASE 2; DIHYDROFOLATE REDUCTASE; FOLIC ACID; LACTAM DERIVATIVE; LIGAND; RNA DIRECTED DNA POLYMERASE; THERMOLYSIN; THROMBIN; UNCLASSIFIED DRUG;

ALGORITHM; ARTICLE; CHEMICAL BOND; CHEMICAL PARAMETERS; CHEMICAL STRUCTURE; COMPUTER AIDED DESIGN; CONTROLLED STUDY; CRYSTAL STRUCTURE; DATA ANALYSIS SOFTWARE; DRUG CONFORMATION; DRUG STRUCTURE; HYDROGEN BOND; HYDROPHOBICITY; LITERATURE; PHARMACEUTICAL ENGINEERING; PHARMACOPHORE; PRIORITY JOURNAL; SEQUENCE ALIGNMENT; STEREOCHEMISTRY;

EID: 34249022980     PISSN: 0920654X     EISSN: 15734951     Source Type: Journal    
DOI: 10.1007/s10822-006-9082-y     Document Type: Article

References (33)

1. Kubinyi H, Folkers G, Martin YC (eds) (1998) 3D QSAR in drug design. Kluwer/ESCOM, Leiden
2. Ferguson AM, Heritage T, Jonathon P, Pack SE, Phillips L, Rogan J, Snaith PJ (1997) J Comput Aided Mol Des 11:143
3. Pastor M, Cruciani G, McLay I, Pickett S, Clementi S (2000) J Med Chem 43:3233
4. Cramer RD III, Patterson DE, Bunce JD (1988) J Am Chem Soc 110:5959
5. Klebe G, Abraham U, Mietzner T (1994) J Med Chem 37:4130
6. Clark RD, Abrahamian E, Strizhev A, Wolohan PRN, Abrams C (2005) 230th ACS National Meeting, Washington, COMP 137
7. Clark RD, Abrahamian E, Abrams C, Brandt P, Gustavsson A-L, Homan E, Metwally E, Richmond NJ, Strizhev A, Wirstam M, Wolohan P (manuscript in preparation)
8. Lemmen C, Lengauer T (2000) J Comput Aided Mol Des 14:215
9. Vladutz G, Gould SR (1988) In: Warr WA (ed) Chemical structures. The international language of chemistry. Springer, Berlin Heidelberg New York, pp 371-384
10. Brown RD, Downs GM, Jones G, Willett P (1994) J Chem Inf Comput Sci 34:47
11. Brown N, Willett P, Wilton DJ, Lewis RA (2003) J Chem Inf Comput Sci 43:288
12. Palyulin VA, Radchenko EV, Zefirov NS (2000) J Chem Inf Comput Sci 40:659
13. Raymond JW, Willett P (2002) J Comput Aided Mol Des 16:521
14. Richmond NJ, Willett P, Clark RD (2004) J Mol Graph Model 23:199
15. GALAHAD™ is distributed by Tripos, Inc., 1699 S. Hanley Rd., St. Louis MO 63144 USA, http://www.tripos.com
16. Patel Y, Gillet V, Bravi G, Leach AR (2002) J Comput Aided Mol Des 16:653
17. Belongie S, Malik J, Puzicha J (2002) IEEE Trans Pattern Anal Mach Intell 24:509
18. Abrahamian E, Fox PC, Nærum L, Christensen IT, Thøgersen H, Clark RD (2003) J Chem Inf Comput Sci 43:458
19. Murtagh F (1983) Comput J 26:354
20. Barnard JM, Downs GM (1992) J Chem Inf Comput Sci 32:644
21. Individual molecules have conformations but the accompanying position in space - the configuration - is only meaningful in relation to another molecule, e.g., in complex wth a protein or in a hypermolecular alignment
22. Jones G, Willett P, Glen RC (1995) J Comput Aided Mol Des 9:532
23. GASP™ is distributed by Tripos, Inc., 1699 S. Hanley Rd., St. Louis MO 63144 USA, http://www.tripos.com
24. Ghose AK, Crippen GM (1982) J Med Chem 25:892
25. SYBYL® is distributed by Tripos, Inc., 1699 S. Hanley Rd., St. Louis MO 63144 USA, http://www.tripos.com
26. 3-H tautomers shown in Fig. 3. The exact choice of tautomer provided to the program may affect the hydrogen bonding strength (gasp weight) assigned to each feature, but will generally have little or no qualitative effect on the models produced
27. Cottrell SJ, Gillet VJ, Taylor R, Wilton DJ (2004) J Comput Aided Mol Des 18:665
28. a of anilines can fall above or below physiological pH values, depending on exactly how they are substituted. Modifying the macro definitions to account for the fact that the exo nitrogens in aminopterins are not basic has no affect on the results shown in Fig. 3 aside from the disappearance of A3 from the model query
29. 1NH
30. Langer, T (2005) Fifth European Workshop in Drug Design, Siena, Italy, 29 May-5 June 2005, http://www.unisi.it/EWDD, http://www.inteligand.com/ demos/cdk2-workshop-siena.pdf
31. Mason JS, Good AC, Martin EJ (2001) Curr Pharm Des 7:567
32. Shepphird JK, Clark RD (2006) J Comput Aided Mol Design (in press)
33. Cole JC, Murray CW, Nissink JW, Taylor RD, Taylor R (2005) Proteins 60:325