Distance Dependent Scoring Function for Describing Protein−Ligand Intermolecular Interactions
- 22 February 2008
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Chemical Information and Modeling
- Vol. 48 (3) , 569-574
- https://doi.org/10.1021/ci700224e
Abstract
A new empirical scoring function has been developed to estimate the binding affinity of a protein−ligand complex with known three-dimensional structure. The scoring function includes a small number of physicochemical descriptors and a large number of quasi-fragmental descriptors. The first group of descriptors is chosen from the following set: (1) the number of close nonbonded contacts, (2) a score for ‘metal-atom' interactions, (3) the number of flexible bonds, (4) van der Waals interaction energy, and (5) electrostatic interaction energy. A training set of 288 ‘protein−ligand' complexes was used to develop the scoring function. The key benefit of this approach is that it reduces the computational complexity while maintaining similar predictive ability to existing methods (average for independent test sets is 2−2.2 kcal/mol). The quasi-fragmental descriptors provide a unique and novel way of accurately representing physical interactions, compared to using physicochemical ones alone.Keywords
This publication has 15 references indexed in Scilit:
- Contribution of Conformer Focusing to the Uncertainty in Predicting Free Energies for Protein−Ligand BindingJournal of Medicinal Chemistry, 2006
- POEM: Parameter Optimization Using Ensemble Methods: Application to Target Specific Scoring FunctionsJournal of Chemical Information and Modeling, 2005
- Approaches to the Description and Prediction of the Binding Affinity of Small-Molecule Ligands to Macromolecular ReceptorsAngewandte Chemie International Edition in English, 2002
- Simple, Intuitive Calculations of Free Energy of Binding for Protein−Ligand Complexes. 1. Models without Explicit Constrained WaterJournal of Medicinal Chemistry, 2002
- How Does Consensus Scoring Work for Virtual Library Screening? An Idealized Computer ExperimentJournal of Chemical Information and Computer Sciences, 2001
- Knowledge-based scoring function to predict protein-ligand interactionsJournal of Molecular Biology, 2000
- The Protein Data BankNucleic Acids Research, 2000
- All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of ProteinsThe Journal of Physical Chemistry B, 1998
- Prediction of binding constants of protein ligands: A fast method for the prioritization of hits obtained from de novo design or 3D database search programsJournal of Computer-Aided Molecular Design, 1998
- Multiple Highly Diverse Structures Complementary to Enzyme Binding Sites: Results of Extensive Application of a de Novo Design Method Incorporating Combinatorial GrowthJournal of the American Chemical Society, 1994