Effect of input differences on the results of docking calculations

  • Feher M
  • Williams C
  • 68

    Readers

    Mendeley users who have this article in their library.
  • 36

    Citations

    Citations of this article.

Abstract

The sensitivity of docking calculations to the geometry of the input ligand was studied. It was found that even small changes in the ligand input conformation can lead to large differences in the geometries and scores of the resulting docked poses. The accuracy of docked poses produced from different ligand input structures?the X-ray structure, the minimized Corina structure, and structures generated from conformational searches and molecular dynamics ensembles?were also assessed. It was found that using the X-ray ligand conformation as docking input does not always produce the most accurate docked pose when compared with other sources of ligand input conformations. Furthermore, no one method of conformer generation is guaranteed to always produce the most accurate docking pose. The docking scores are also highly sensitive to the source of the input conformation, which might introduce some noise in compound ranking and in binding affinity predictions. It is concluded that for the purposes of reproducibility and optimal performance, the most prudent procedure is to use multiple input structures for docking. The implications of these results on docking validation studies are discussed. The sensitivity of docking calculations to the geometry of the input ligand was studied. It was found that even small changes in the ligand input conformation can lead to large differences in the geometries and scores of the resulting docked poses. The accuracy of docked poses produced from different ligand input structures?the X-ray structure, the minimized Corina structure, and structures generated from conformational searches and molecular dynamics ensembles?were also assessed. It was found that using the X-ray ligand conformation as docking input does not always produce the most accurate docked pose when compared with other sources of ligand input conformations. Furthermore, no one method of conformer generation is guaranteed to always produce the most accurate docking pose. The docking scores are also highly sensitive to the source of the input conformation, which might introduce some noise in compound ranking and in binding affinity predictions. It is concluded that for the purposes of reproducibility and optimal performance, the most prudent procedure is to use multiple input structures for docking. The implications of these results on docking validation studies are discussed.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Miklos Feher

  • Christopher I. Williams

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free