<br/>Conformational differences between free and ligand-bound protein structures can make computational docking of small molecule ligands into proteins difficult. Our information-driven docking approach HADDOCK, which does account for flexibility in both receptor and ligand, has been mainly applied to protein-protein, protein-DNA/RNA, and protein-peptide docking problems. Here we present the results of its application to a benchmark of 76 Native protein-ligand complexes from the Astex Diverse Set (redocking), concentrating on Unbound (cross-docking) cases for 56 of those native complexes from the Astex Non-Native Set. For the current work, an optimized protein-ligand docking protocol was developed.<br/>Overall HADDOCK performance (top-scoring cluster with ligand-RMSD &lt; 2Å) on the benchmark set of Native cases (redocking) was over 79% using ligand-specific protocols, and generated a top5-scoring solution in over 92% of all 76 Native cases.<br/>For the Unbound cases (each Native case represented by an apo-structure and/or a structure crystallized with a different ligand), the overall success of HADDOCK was up to 62% of cases, and a top5-scoring solution in up to 81% of the Unbound cases. Using ensembles of Unbound protein structures as input allows assessment of how protein conformation influences docking success.

Ensemble HADDOCKing and performance on a benchmark of protein-ligand complexes

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.