Abstract
BackgroundIs it possible to identify what the best solution of a docking program is? The usual answer to this question is the highest score solution, but interactions between proteins are dynamic processes, and many times the interaction regions are wide enough to permit protein-protein interactions with different orientations and/or interaction energies. In some cases, as in a multimeric protein complex, several interaction regions are possible among the monomers. These dynamic processes involve interactions with surface displacements between the proteins to finally achieve the functional configuration of the protein complex. Consequently, there is not a static and single solution for the interaction between proteins, but there are several important configurations that also have to be analyzed.ResultsTo extract those representative solutions from the docking output datafile, we have developed an unsupervised and automatic clustering application, named DockAnalyse. This application is based on the already existing DBscan clustering method, which searches for continuities among the clusters generated by the docking output data representation. The DBscan clustering method is very robust and, moreover, solves some of the inconsistency problems of the classical clustering methods like, for example, the treatment of outliers and the dependence of the previously defined number of clusters.ConclusionsDockAnalyse makes the interpretation of the docking solutions through graphical and visual representations easier by guiding the user to find the representative solutions. We have applied our new approach to analyze several protein interactions and model the dynamic protein interaction behavior of a protein complex. DockAnalyse might also be used to describe interaction regions between proteins and, therefore, guide future flexible dockings. The application (implemented in the R package) is accessible.
Highlights
Is it possible to identify what the best solution of a docking program is? The usual answer to this question is the highest score solution, but interactions between proteins are dynamic processes, and many times the interaction regions are wide enough to permit protein-protein interactions with different orientations and/or interaction energies
Nuclear Magnetic Resonance (NMR) and X-Ray Crystallography (XRC) are the two main technologies applied for structure elucidation, but these hi-tech methods are frequently constrained by the methodological requirements when dealing with protein complexes
It is assumed that these experimental limitations have reduced the amount of large protein complexes solved and, protein complexes have become less represented in the structural databases such as the Protein Data Bank (PDB; http://www.rcsb.org/pdb/home/ home.do; [12])
Summary
Is it possible to identify what the best solution of a docking program is? The usual answer to this question is the highest score solution, but interactions between proteins are dynamic processes, and many times the interaction regions are wide enough to permit protein-protein interactions with different orientations and/or interaction energies. Despite the use of these two experimental technologies for protein structure determination being widely distributed, other complementary strategies may be useful to accurately model the dynamics of the interaction among the proteins of a protein complex. In this context, some theoretical methods to study protein complexes at a structural level, such as docking, are emerging. In rigid body PPD approaches, conformational changes during the complex formation are not permitted, in order to save computation time This technique may be appropriate when non-substantial conformational changes are expected to take place in the interacting proteins
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