Molecular docking performance evaluated on the D3R Grand Challenge 2015 drug-like ligand datasets

J Comput Aided Mol Des. 2016 Sep;30(9):829-839. doi: 10.1007/s10822-016-9983-3. Epub 2016 Oct 3.

Abstract

The D3R Grand Challenge 2015 was focused on two protein targets: Heat Shock Protein 90 (HSP90) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4). We used a protocol involving a preliminary analysis of the available data in PDB and PubChem BioAssay, and then a docking/scoring step using more computationally demanding parameters that were required to provide more reliable predictions. We could evidence that different docking software and scoring functions can behave differently on individual ligand datasets, and that the flexibility of specific binding site residues is a crucial element to provide good predictions.

Keywords: Autodock; D3R Grand Challenge 2015; Docking; Glide; Gold; HSP90; Heat Shock Protein 90; MAP4K4; Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4; Scoring function.

MeSH terms

  • Algorithms
  • Binding Sites
  • Databases, Protein
  • Drug Design
  • HSP90 Heat-Shock Proteins / chemistry*
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Ligands
  • Molecular Docking Simulation / methods*
  • Protein Binding
  • Protein Conformation*
  • Protein Serine-Threonine Kinases / chemistry*
  • Structure-Activity Relationship

Substances

  • HSP90 Heat-Shock Proteins
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • MAP4K4 protein, human
  • Protein Serine-Threonine Kinases