Development of purely structure-based pharmacophores for the topoisomerase I-DNA-ligand binding pocket.

ABSTRACT: Purely structure-based pharmacophores (SBPs) are an alternative method to ligand-based approaches and have the advantage of describing the entire interaction capability of a binding pocket. Here, we present the development of SBPs for topoisomerase I, an anticancer target with an unusual ligand binding pocket consisting of protein and DNA atoms. Different approaches to cluster and select pharmacophore features are investigated, including hierarchical clustering and energy calculations. In addition, the performance of SBPs is evaluated retrospectively and compared to the performance of ligand- and complex-based pharmacophores. SBPs emerge as a valid method in virtual screening and a complementary approach to ligand-focussed methods. The study further reveals that the choice of pharmacophore

SUBMITTER: Drwal MN 

PROVIDER: S-EPMC7578780 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature