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. 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. BEAR is fast, modular and automated, and can be applied to virtual screenings against any biological target with known structure and any database of compounds, regardless of the docking method used for generating the initial pose.
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. 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. BEAR is fast, modular and automated, and can be applied to virtual screenings against any biological target with known structure and any database of compounds, regardless of the docking method used for generating the initial pose.
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