Ensemble-Based Virtual Screening (EB-VS) uses docking against multiple conformations of a target protein—often derived from molecular dynamics simulations, NMR, X-ray crystallography, or cryo-EM to screen compound libraries for potential binders. This method accounts for protein flexibility (typically not considered by docking programs), improving the identification of ligands that may bind to different or transient conformational states. Clustering can aid the selection of diverse and relevant conformations to minimize redundancy within ensembles.
Importance in Computational Drug Discovery:
- Captures protein flexibility, leading to more accurate identification of potential drug candidates compared to single-structure screening.
- May increase hit rates by accommodating diverse ligand binding modes and cryptic binding sites.
- Helps identify allosteric modulators and ligands that stabilize specific protein conformations.
- Reduces false negatives that may arise from rigid-receptor assumptions in traditional virtual screening.
- Supports rational drug design by providing insights into the dynamic nature of protein-ligand interactions.
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