Coupling structure-based design with combinatorial chemistry: Application of active site derived pharmacophores with informative library design

Journal of Molecular Graphics and Modelling

Volumn 20, Issue 6, 2002, Pages 469-477

  Eksterowicz, John E ^a   Evensen, Erik ^a   Lemmen, Christian ^a   Patrick Brady, G ^b   Kevin Lanctot, J ^a   Bradley, Erin K ^a   Saiah, Eddine ^b   Robinson, Leslie A ^b   Grootenhuis, Peter D J ^b   Blaney, Jeffrey M ^a  

^a DuPont Pharmaceuticals Research Laboratories   (United States)

^b DUPONT COMPANY   (United States)

Author keywords

Combinatorial chemistry; Cyclin dependent kinase; Informative library design; Pharmacophore; Site map; Structure based design

Indexed keywords

ASSAYS; CRYSTAL STRUCTURE; PROTEINS;

COMBINATORIAL LIBRARY DESIGN;

MOLECULAR GRAPHICS;

CYCLIN DEPENDENT KINASE 2; PROTEIN; CYCLIN DEPENDENT KINASE; PROTEIN SERINE THREONINE KINASE;

COMBINATORIAL CHEMISTRY; COMBINATORIAL LIBRARY; CONFERENCE PAPER; ENZYMATIC ASSAY; ENZYME ACTIVE SITE; EXPERIMENTAL DESIGN; INFORMATION; MATHEMATICAL COMPUTING; METHODOLOGY; PHARMACOPHORE; PRIORITY JOURNAL; PROTEIN STRUCTURE; X RAY CRYSTALLOGRAPHY; ALGORITHM; ARTICLE; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; COMPUTER PROGRAM; DRUG DESIGN; FACTUAL DATABASE; LIBRARY; METABOLISM; PROTEIN TERTIARY STRUCTURE; QUANTITATIVE STRUCTURE ACTIVITY RELATION; STRUCTURE ACTIVITY RELATION;

ALGORITHMS; BINDING SITES; CDC2-CDC28 KINASES; CHEMISTRY, PHARMACEUTICAL; COMBINATORIAL CHEMISTRY TECHNIQUES; CRYSTALLOGRAPHY, X-RAY; CYCLIN-DEPENDENT KINASE 2; CYCLIN-DEPENDENT KINASES; DATABASES, FACTUAL; DRUG DESIGN; LIBRARIES; MOLECULAR STRUCTURE; PROTEIN STRUCTURE, TERTIARY; PROTEIN-SERINE-THREONINE KINASES; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; SOFTWARE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0036010705     PISSN: 10933263     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1093-3263(01)00148-6     Document Type: Conference Paper

References (35)

1. Managing the drug discovery process
2. Three-dimensional hydrogen-bond geometry and probability information from a crystal survey
3. Functionality maps of binding sites: A multiple copy simultaneous search method
4. Pharmacophore-based molecular docking
5. Pharmacophore-based molecular docking. Pharmacophore perception, development and use in drug design (Iul biotechnology series, 2)
6. Adapting structure-based drug design in the paradigm of combinatorial chemistry and high-throughput screening: An overview and new examples with important caveats for newcomers to combinatorial library design using pharmacophore models or multiple copy simultaneous search fragments
7. Design of libraries to explore receptor sites
8. Library design and virtual screening using multiple 4-point pharmacophore fingerprints
9. New 4-point pharmacophore method for molecular similarity and diversity applications: Overview of the method and applications, including a novel approach to the design of combinatorial libraries containing privileged substructures
10. Developing a dynamic pharmacophore model for HIV-1 integrase
11. Novel inhibitors of DNA gyrase: 3D structure based biased needle screening, hit validation by biophysical methods, and 3D guided optimization. A promising alternative to random screening
12. Ligand-receptor 3-D similarity studies using multiple 4-point pharmacophores
13. Informative libraries are more useful than diverse ones
14. The design of informative libraries
15. High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP: Bound waters and natural ligand as guides for inhibitor design
16. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors
17. Inhibition of cyclin-dependent kinases, GSK-3.beta. and CK1 by hymenialdisine, a marine sponge constituent
18. Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex
19. Recent applications of solution phase parallel synthesis to kinas inhibitor libraries
20. Fast prediction and visualization of protein binding pockets with PASS
21. Structure and energetics of ligand binding to proteins: Escherichia coli dihydrofolate reductase-trimethoprim, a drug-receptor system
22. Hydrogen bond stereochemistry in protein structure and function
23. Prediction of ligand-binding modes via energy-based genetic algorithm docking
24. Pharmacophore fingerprinting. 1. Application to QSAR and focused library design
25. Addressing the challenges of combinatorial chemistry: 3D databases, pharmacophore recognition and beyond
26. Conformational analysis by intersection: Ring conformations
27. Molecular recognition of the inhibitor AG-1343 by HIV-1 protease: Conformationally flexible docking by evolutionary programming