Skip to main content
  • Poster presentation
  • Open access
  • Published:

The assessment of computationally derived protein ensembles in protein-ligand docking

The inclusion of receptor flexibility in protein-ligand docking experiments has become a major research interest in drug discovery [1, 2]. One of the possible methods applied is the use of multiple discrete protein conformations, so called ensemble docking [3, 4]. With computational techniques like Molecular Dynamics (MD) a large number of different conformations can be generated, not all of which can or should be included in the docking or virtual screening process [5]. The question arises if and how suitable protein conformations can be selected systematically a priori based on quantifiable conformational features.

For neuraminidase and cyclin-dependent kinase II (CDK2), snapshots of MD simulation trajectories have been clustered based on different structural properties using a variety of clustering methods. To establish a possible correlation between docking performance and target conformational attributes the clustered snapshots have been subjected to extensive self- and cross-docking experiments as well as virtual screening using the GOLD docking programme. It is shown that conformationally similar snapshots do not necessarily result in a similar docking or virtual screening performance. The selection of the particular structural property on which to base the clustering appears to be the essential problem.


  1. Carlson HA: Protein flexibility and drug design: how to hit a moving target. Curr Opin Chem Biol. 2002, 6: 447-452. 10.1016/S1367-5931(02)00341-1.

    Article  CAS  Google Scholar 

  2. Durrant JD, McCammon JA: Computer-aided drug-discovery techniques that account for receptor flexibility. Curr Opin Pharmacol. 2010, 10: 770-774. 10.1016/j.coph.2010.09.001.

    Article  CAS  Google Scholar 

  3. Barril X, Morley DS: Unveiling the full potential of flexible receptor docking using multiple crystallographic structures. J Med Chem. 2005, 48: 4432-4443. 10.1021/jm048972v.

    Article  CAS  Google Scholar 

  4. Huang S-Y, Zou H: Ensemble docking of multiple protein structures: considering protein structural variations in molecular docking. Proteins. 2007, 66: 399-421.

    Article  CAS  Google Scholar 

  5. Lin J-H, Perryman AL, Schames JR, McCammon JA: Computational drug design accomodating receptor flexibility: the relaxed complex scheme. J Am Chem Soc. 2002, 124: 5632-5633. 10.1021/ja0260162.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Barbara Sander.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

Sander, B., Korb, O., Cole, J. et al. The assessment of computationally derived protein ensembles in protein-ligand docking. J Cheminform 4 (Suppl 1), P34 (2012).

Download citation

  • Published:

  • DOI: