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The assessment of computationally derived protein ensembles in protein-ligand docking
Journal of Cheminformatics volume 4, Article number: P34 (2012)
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 . 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.
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Sander, B., Korb, O., Cole, J. et al. The assessment of computationally derived protein ensembles in protein-ligand docking. J Cheminform 4, P34 (2012). https://doi.org/10.1186/1758-2946-4-S1-P34
- Virtual Screening
- Protein Conformation
- Simulation Trajectory
- Docking Programme
- Docking Experiment