Tan Lu, Lounkine Eugen, Bajorath Jürgen
Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and MedicinalChemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstrasse 2, D-53113 Bonn, Germany.
J Chem Inf Model. 2008 Dec;48(12):2308-12. doi: 10.1021/ci800322y.
To incorporate protein-ligand interaction information into conventional two-dimensional (2D) fingerprint searching, interacting fragments of active compounds were extracted from X-ray structures of protein-ligand complexes and encoded as structural key-type fingerprints. Similarity search calculations with fingerprints derived from interacting fragments were compared to fingerprints of complete ligands and control fragments. In these calculations, fingerprints of interacting fragments produced significantly higher compound recall than other fingerprints. These results indicate that ligand fragments involved in protein-ligand interactions carry much activity-specific chemical information that can be exploited in similarity searching without explicitly accounting for interaction information.
为了将蛋白质-配体相互作用信息纳入传统的二维（2D）指纹搜索中，从蛋白质-配体复合物的X射线结构中提取活性化合物的相互作用片段，并将其编码为结构键型指纹。将源自相互作用片段的指纹进行的相似性搜索计算与完整配体和对照片段的指纹进行了比较。在这些计算中，相互作用片段的指纹产生的化合物召回率明显高于其他指纹。这些结果表明，参与蛋白质-配体相互作用的配体片段携带了许多活性特异性化学信息，这些信息可用于相似性搜索，而无需明确考虑相互作用信息。
