DINC-COVID

DINC-COVID performs ensemble docking using representative SARS-CoV-2 protein conformations to account for receptor flexibility and predict ligand binding affinities.

Key Features:

• Ensemble docking: Performs docking across multiple protein conformations to incorporate receptor flexibility into binding predictions.
• Representative conformations: Uses ensembles of protein conformations derived from the Protein Data Bank and in silico molecular dynamics simulations.
• Pre-computed ensembles: Provides twelve pre-computed ensembles of SARS-CoV-2 protein conformations capturing diverse receptor flexibilities.
• Alternative binding modes: Enables identification of alternative ligand binding modes that may be missed by rigid docking approaches.
• Binding energy scoring: Produces docking-derived binding energies for evaluation of ligand affinity.
• Validation datasets: Was validated using datasets of tested inhibitors against two specific SARS-CoV-2 proteins.
• Correlation with experiments: Validation demonstrated strong correlations between docking-derived binding energies and experimentally determined binding affinities.
• Large-ligand applicability: Shows particularly strong performance with large ligands resolved by room temperature crystallography.

Scientific Applications:

• Predicting ligand affinities: Estimating binding affinities of small molecules to SARS-CoV-2 proteins while accounting for receptor flexibility.
• Identifying alternative binding modes: Detecting alternative ligand poses enabled by diverse protein conformations.
• Virtual screening with receptor dynamics: Supporting virtual screening workflows that incorporate conformational ensembles of viral proteins.
• Benchmarking docking results: Comparing docking-derived binding energies to experimental binding affinities for validation studies.
• Studying large ligands: Evaluating binding of large ligands informed by room temperature crystallography data.

Methodology:

Representative ensembles were obtained from the Protein Data Bank and in silico molecular dynamics simulations, ensemble docking was performed to produce docking-derived binding energies, and those energies were compared to experimental binding affinities for validation.