DSX: A Knowledge-Based Scoring Function for the Assessment of Protein–Ligand Complexes
- 4 October 2011
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Chemical Information and Modeling
- Vol. 51 (10), 2731-2745
- https://doi.org/10.1021/ci200274q
Abstract
We introduce the new knowledge-based scoring function DSX that consists of distance-dependent pair potentials, novel torsion angle potentials, and newly defined solvent accessible surface-dependent potentials. DSX pair potentials are based on the statistical formalism of DrugScore, extended by a much more specialized set of atom types. The original DrugScore-like reference state is rather unstable with respect to modifications in the used atom types. Therefore, an important method to overcome this problem and to allow for robust results when deriving pair potentials for arbitrary sets of atom types is presented. A validation based on a carefully prepared test set is shown, enabling direct comparison to the majority of other popular scoring functions. Here, DSX features superior performance with respect to docking- and ranking power and runtime requirements. Furthermore, the beneficial combination with torsion angle-dependent and desolvation-dependent potentials is demonstrated. DSX is robust, flexible, and capable of working together with special features of popular docking engines, e.g., flexible protein residues in AutoDock or GOLD. The program is freely available to the scientific community and can be downloaded from our Web site www.agklebe.de .Keywords
This publication has 57 references indexed in Scilit:
- eHiTS: A new fast, exhaustive flexible ligand docking systemJournal of Molecular Graphics and Modelling, 2007
- Extra Precision Glide: Docking and Scoring Incorporating a Model of Hydrophobic Enclosure for Protein−Ligand ComplexesJournal of Medicinal Chemistry, 2006
- Glide: A New Approach for Rapid, Accurate Docking and Scoring. 1. Method and Assessment of Docking AccuracyJournal of Medicinal Chemistry, 2004
- DOCK 4.0: Search strategies for automated molecular docking of flexible molecule databasesJournal of Computer-Aided Molecular Design, 2001
- Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy functionJournal of Computational Chemistry, 1998
- Development and validation of a genetic algorithm for flexible dockingJournal of Molecular Biology, 1997
- A Fast Flexible Docking Method using an Incremental Construction AlgorithmJournal of Molecular Biology, 1996
- Distributed automated docking of flexible ligands to proteins: Parallel applications of AutoDock 2.4Journal of Computer-Aided Molecular Design, 1996
- Molecular recognition of receptor sites using a genetic algorithm with a description of desolvationJournal of Molecular Biology, 1995
- Automated docking of substrates to proteins by simulated annealingProteins, 1990