title: Target Flexibility in RNA-Ligand Docking Modeled by Elastic Potential Grids.
abstract: The highly flexible nature of RNA provides a formidable challenge for structure-based drug design approaches that target RNA. We introduce an approach for modeling target conformational changes in RNA-ligand docking based on potential grids that are represented as elastic bodies using Navier's equation. This representation provides an accurate and efficient description of RNA-ligand interactions even in the case of a moving RNA structure. When applied to a data set of 17 RNA-ligand complexes, filtered out of the largest validation data set used for RNA-ligand docking so far, the approach is twice as successful as docking into an apo structure and still half as successful as redocking to the holo structure. The approach allows considering RNA movements of up to 6 Å rmsd and is based on a uniform and robust parametrization of the properties of the elastic potential grids, so that the approach is applicable to different RNA-ligand complex classes.
authors.affiliation: Department of Mathematics and Natural Sciences, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich-Heine-University , Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Krüger
authors.affiliation: Department of Mathematics and Natural Sciences, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich-Heine-University , Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Bergs
authors.affiliation: Department of Mathematics and Natural Sciences, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich-Heine-University , Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Sina
authors.initials: S
authors.lastname: Kazemi
authors.affiliation: Department of Mathematics and Natural Sciences, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich-Heine-University , Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Gohlke
keywords: DrugScore; RNA−ligand interactions; elasticity theory; flexible docking; structure-based drug design