The authors state no conflict of interest.
Present and future challenges and limitations in protein–protein docking†
Article first published online: 5 AUG 2009
Copyright © 2009 Wiley-Liss, Inc.
Proteins: Structure, Function, and Bioinformatics
Special Issue: Special Issue in Memoriam of Angel R. Ortiz
Volume 78, Issue 1, pages 95–108, January 2010
How to Cite
Pons, C., Grosdidier, S., Solernou, A., Pérez-Cano, L. and Fernández-Recio, J. (2010), Present and future challenges and limitations in protein–protein docking. Proteins, 78: 95–108. doi: 10.1002/prot.22564
- Issue published online: 27 NOV 2009
- Article first published online: 5 AUG 2009
- Accepted manuscript online: 5 AUG 2009 12:00AM EST
- Manuscript Accepted: 16 JUL 2009
- Manuscript Revised: 4 JUL 2009
- Manuscript Received: 7 APR 2009
- The Spanish Ministry of Science. Grant Number: BIO2008-02882
- protein–protein docking;
- Fast Fourier transform;
- molecular recognition;
The study of protein–protein interactions that are involved in essential life processes can largely benefit from the recent upraising of computational docking approaches. Predicting the structure of a protein–protein complex from their separate components is still a highly challenging task, but the field is rapidly improving. Recent advances in sampling algorithms and rigid-body scoring functions allow to produce, at least for some cases, high quality docking models that are perfectly suitable for biological and functional annotations, as it has been shown in the CAPRI blind tests. However, important challenges still remain in docking prediction. For example, in cases with significant mobility, such as multidomain proteins, fully unrestricted rigid-body docking approaches are clearly insufficient so they need to be combined with restraints derived from domain–domain linker residues, evolutionary information, or binding site predictions. Other challenging cases are weak or transient interactions, such as those between proteins involved in electron transfer, where the existence of alternative bound orientations and encounter complexes complicates the binding energy landscape. Docking methods also struggle when using in silico structural models for the interacting subunits. Bringing these challenges to a practical point of view, we have studied here the limitations of our docking and energy-based scoring approach, and have analyzed different parameters to overcome the limitations and improve the docking performance. For that, we have used the standard benchmark and some practical cases from CAPRI. Based on these results, we have devised a protocol to estimate the success of a given docking run. Proteins 2010. © 2009 Wiley-Liss, Inc.