Bioactive Conformational Biasing: A New Method for Focusing Conformational Ensembles on Bioactive-Like Conformers
Boaz Musafia, Hanoch Senderowitz · Journal of Chemical Information and Modeling · 2009
Computational approaches that rely on ligand-based information for lead discovery and optimization are often required to spend considerable resources analyzing compounds with large conformational ensembles. In order to reduce such efforts, we have developed a new filtration tool which reduces the total number of ligand conformations while retaining in the final set a reasonable number of conformations that are similar (rmsd 2.5 A) from the bioactive conformer (nonbioactive conformations). In accord with previous reports, prefiltration is shown to have a major effect on model performance. The role and performance of specific descriptors as filters is discussed in some detail, and future directions are proposed.