Chemical Substructures that Enrich for Biological Activity. Export

@article{citeulike:3328889, abstract = {MOTIVATION: Certain chemical substructures are present in many drugs. This has led to the claim of "privileged" substructures which are pre-disposed to bioactivity. Because bias in screening library construction could explain this phenomenon, the existence of privi-lege has been controversial. Using diverse phenotypic assays, we defined bioactivity for multiple compound libraries. Many substruc-tures were associated with bioactivity even after accounting for substructure prevalence in the library, thus validating the privileged substructure concept. Determinations of privilege were confirmed in independent assays and libraries. Our analysis also revealed "underprivileged" substructures and "conditional privilege"-rules relating combinations of substructure to bioactivity. Most previously-reported substructures have been flat aromatic ring systems. Although we validated such substructures, we also identified three-dimensional privileged substructures. Most privileged substructures display a wide variety of substituents, suggesting an entropic mechanism of privilege. Compounds containing privileged substructures had a doubled rate of bioactivity, suggesting practical consequences for pharmaceutical discovery.}, address = {Harvard University Graduate Biophysics Program.}, author = {Klekota, Justin and Roth, Frederick P P.}, citeulike-article-id = {3328889}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/bioinformatics/btn479}, citeulike-linkout-1 = {http://bioinformatics.oxfordjournals.org/cgi/content/abstract/24/21/2518}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18784118}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18784118}, day = {11}, doi = {10.1093/bioinformatics/btn479}, issn = {1460-2059}, journal = {Bioinformatics (Oxford, England)}, keywords = {analysis, bioinformatics, chemgen}, month = {September}, posted-at = {2008-11-06 10:54:45}, priority = {2}, title = {Chemical Substructures that Enrich for Biological Activity.}, url = {http://dx.doi.org/10.1093/bioinformatics/btn479}, year = {2008} }

TY - JOUR ID - citeulike:3328889 L3 - citeulike-article-id:3328889 N2 - MOTIVATION: Certain chemical substructures are present in many drugs. This has led to the claim of "privileged" substructures which are pre-disposed to bioactivity. Because bias in screening library construction could explain this phenomenon, the existence of privi-lege has been controversial. Using diverse phenotypic assays, we defined bioactivity for multiple compound libraries. Many substruc-tures were associated with bioactivity even after accounting for substructure prevalence in the library, thus validating the privileged substructure concept. Determinations of privilege were confirmed in independent assays and libraries. Our analysis also revealed "underprivileged" substructures and "conditional privilege"-rules relating combinations of substructure to bioactivity. Most previously-reported substructures have been flat aromatic ring systems. Although we validated such substructures, we also identified three-dimensional privileged substructures. Most privileged substructures display a wide variety of substituents, suggesting an entropic mechanism of privilege. Compounds containing privileged substructures had a doubled rate of bioactivity, suggesting practical consequences for pharmaceutical discovery. JF - Bioinformatics (Oxford, England) SN - 1460-2059 AD - Harvard University Graduate Biophysics Program. TI - Chemical Substructures that Enrich for Biological Activity. KW - analysis KW - bioinformatics KW - chemgen AU - Klekota, Justin AU - Roth, Frederick P PY - 2008/09/11/ UR - http://dx.doi.org/10.1093/bioinformatics/btn479 ER -