Scaffold hopping using clique detection applied to reduced graphs. Export

@article{citeulike:780812, abstract = {Similarity-based methods for virtual screening are widely used. However, conventional searching using 2D chemical fingerprints or 2D graphs may retrieve only compounds which are structurally very similar to the original target molecule. Of particular current interest then is scaffold hopping, that is, the ability to identify molecules that belong to different chemical series but which could form the same interactions with a receptor. Reduced graphs provide summary representations of chemical structures and, therefore, offer the potential to retrieve compounds that are similar in terms of their gross features rather than at the atom-bond level. Using only a fingerprint representation of such graphs, we have previously shown that actives retrieved were more diverse than those found using Daylight fingerprints. Maximum common substructures give an intuitively reasonable view of the similarity between two molecules. However, their calculation using graph-matching techniques is too time-consuming for use in practical similarity searching in larger data sets. In this work, we exploit the low cardinality of the reduced graph in graph-based similarity searching. We reinterpret the reduced graph as a fully connected graph using the bond-distance information of the original graph. We describe searches, using both the maximum common induced subgraph and maximum common edge subgraph formulations, on the fully connected reduced graphs and compare the results with those obtained using both conventional chemical and reduced graph fingerprints. We show that graph matching using fully connected reduced graphs is an effective retrieval method and that the actives retrieved are likely to be topologically different from those retrieved using conventional 2D methods.}, address = {Department of Information Studies and Krebs Institute for Biomolecular Research, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom.}, author = {Barker, E. J. and Buttar, D. and Cosgrove, D. A. and Gardiner, E. J. and Kitts, P. and Willett, P. and Gillet, V. J.}, citeulike-article-id = {780812}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/ci050347r}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/ci050347r}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16562978}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16562978}, doi = {10.1021/ci050347r}, issn = {1549-9596}, journal = {J Chem Inf Model}, keywords = {graph, reduced, similarity}, number = {2}, pages = {503--511}, posted-at = {2008-01-03 13:27:18}, priority = {2}, title = {Scaffold hopping using clique detection applied to reduced graphs.}, url = {http://dx.doi.org/10.1021/ci050347r}, volume = {46}, year = {2006} }

TY - JOUR ID - citeulike:780812 L3 - citeulike-article-id:780812 N2 - Similarity-based methods for virtual screening are widely used. However, conventional searching using 2D chemical fingerprints or 2D graphs may retrieve only compounds which are structurally very similar to the original target molecule. Of particular current interest then is scaffold hopping, that is, the ability to identify molecules that belong to different chemical series but which could form the same interactions with a receptor. Reduced graphs provide summary representations of chemical structures and, therefore, offer the potential to retrieve compounds that are similar in terms of their gross features rather than at the atom-bond level. Using only a fingerprint representation of such graphs, we have previously shown that actives retrieved were more diverse than those found using Daylight fingerprints. Maximum common substructures give an intuitively reasonable view of the similarity between two molecules. However, their calculation using graph-matching techniques is too time-consuming for use in practical similarity searching in larger data sets. In this work, we exploit the low cardinality of the reduced graph in graph-based similarity searching. We reinterpret the reduced graph as a fully connected graph using the bond-distance information of the original graph. We describe searches, using both the maximum common induced subgraph and maximum common edge subgraph formulations, on the fully connected reduced graphs and compare the results with those obtained using both conventional chemical and reduced graph fingerprints. We show that graph matching using fully connected reduced graphs is an effective retrieval method and that the actives retrieved are likely to be topologically different from those retrieved using conventional 2D methods. IS - 2 JF - J Chem Inf Model SN - 1549-9596 AD - Department of Information Studies and Krebs Institute for Biomolecular Research, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom. EP - 511 TI - Scaffold hopping using clique detection applied to reduced graphs. VL - 46 SP - 503 KW - graph KW - reduced KW - similarity AU - Barker, EJ AU - Buttar, D AU - Cosgrove, DA AU - Gardiner, EJ AU - Kitts, P AU - Willett, P AU - Gillet, VJ PY - 2006///r UR - http://dx.doi.org/10.1021/ci050347r ER -