Although molecular docking is a widely used technique in drug discovery for the identification of hits or lead molecules, the method still retains important weaknesses and limitations. For example, docking techniques still lack reliable simulation of the flexibility of both ligands and receptor, and scoring functions may fail to estimate ligand binding energies in reasonable agreement with experiment. In light of these observations, we focused our efforts on the development, validation and application of a new post-docking tool aimed at overcoming some of these limitations. The method, named BEAR (Binding Estimation After Refinement), is a new automated post-docking procedure based on the conformational refinement of docking poses through molecular dynamics (MD) followed by accurate predictions of protein binding free energies using MM-PBSA and MM-GBSA.
Improving enrichment and hit rates in virtual screening.
Portioli, Corinne
2010-01-01
Abstract
Although molecular docking is a widely used technique in drug discovery for the identification of hits or lead molecules, the method still retains important weaknesses and limitations. For example, docking techniques still lack reliable simulation of the flexibility of both ligands and receptor, and scoring functions may fail to estimate ligand binding energies in reasonable agreement with experiment. In light of these observations, we focused our efforts on the development, validation and application of a new post-docking tool aimed at overcoming some of these limitations. The method, named BEAR (Binding Estimation After Refinement), is a new automated post-docking procedure based on the conformational refinement of docking poses through molecular dynamics (MD) followed by accurate predictions of protein binding free energies using MM-PBSA and MM-GBSA.
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