Computational approaches for combinatorial library design and molecular diversity analysis

Current Opinion in Chemical Biology

Volumn 1, Issue 1, 1997, Pages 54-59

  Blaney, Jeffrey M ^a   Martin, Eric J ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS;

ORGANIC CHEMISTRY; REVIEW; STRUCTURE ACTIVITY RELATION;

CHEMISTRY, ORGANIC; INDICATORS AND REAGENTS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0031152087     PISSN: 13675931     EISSN: None     Source Type: Journal    
DOI: 10.1016/s1367-5931(97)80108-1     Document Type: Article

References (27)

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3. Brown RD, Martin YC: Use of structure-activity data to compare structure-based clustering methods and descriptors for use in compound selection. J Chem Inform Comput Sci 1996, 36:572-584. Compares how several commonly used 2D and 3D diversity descriptors perform in classifying active compounds versus inactive in large, diverse datasets. Concludes that simple 2D descriptors outperform more complicated 3D descriptors.
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7. Brown RD, Martin YC: The information content of 2D and 3D structural descriptors relevant to ligand-receptor binding. J Chem Inform Comput Sci 1997, 37:1-9. Suggests that some simple diversity descriptors correlate with properties known to be critical for intermolecular recognition, and provides a rationale for how 2D descriptors can be so effective.
8. Patterson DE, Cramer RD, Ferguson AM, Clark RD, Weinberger LE: Neighborhood behavior: a useful concept for validation of 'molecular diversity' descriptors. J Med Chem 1996, 39:3049-3059. Novel approach compares differences in diversity descriptors for a series of molecules with differences in their experimental biological behavior and suggests that relevant descriptors show a characteristic 'neighborhood behavior'.
9. Cramer RD, Clark RD, Patterson DE, Ferguson AM: Bioisosterism as a molecular diversity descriptor: steric fields of single 'topomeric' conformers. J Med Chem 1996, 39:3060-3069. Describes a new approach to using conventional 3D-QSAR descriptors for diversity analysis.
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20. Hassan M, Bielawski JP, Hempel JC, Waldman M: Optimization and visualization of molecular diversity of combinatorial libraries. Mol Divers 1996, 2:64-74.
21. Sheridan RP, Kearsley SK: Using a genetic algorithm to suggest combinatorial libraries. J Chem Inform Comput Sci 1995, 35:310-320. The first publication of a genetic algorithm approach to combinatorial library design, applied to a tripeptoid.
22. Goldberg DE: Genetic Algorithms in Search, Optimization, and Machine Learning. New York: Addison-Wesley; 1989.
23. Pearlman RS: Novel software tools for addressing chemical diversity. Network Science 1996, http://www.awod.com/netsci/Science/Combichem/feature08.html This paper describes the unusual BCUT diversity descriptors and cell-based sampling approach from Pearlman. The cell-based approach has intuitive appeal for sampling and finding holes, but the BCUT diversity descriptors relevance is unclear at this point.
24. Agrafiotis DK: Stochastic algorithms for maximizing molecular diversity. Third Electronic Computational Chemistry Conference, The Internet: http://hackberry.chem.niu.edu/ECCC3; 1996.
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26. Pickett SD, Mason JS, McLay IM: Diversity profiling and design using 3D pharmacophores: pharmacophore-derived queries (PDQ). J Chem Inform Comput Sci 1996, 36:1214-1223. Good description of 3D-pharmacophore approach to diversity analysis, including how 3D-pharmacophores are defined and converted into binary descriptors. This work focuses on selecting compounds from databases, not virtual combinatorial libraries.
27. Chapman D: The measurement of molecular diversity: A three-dimensional approach. J Comput Aided Mol Des 1996, 10:501-512.