iBet uBet web content aggregator. Adding the entire web to your favor.
iBet uBet web content aggregator. Adding the entire web to your favor.



Link to original content: https://pubmed.ncbi.nlm.nih.gov/25418159/
Protein-protein docking: from interaction to interactome - PubMed Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Oct 21;107(8):1785-1793.
doi: 10.1016/j.bpj.2014.08.033.

Protein-protein docking: from interaction to interactome

Ilya A Vakser  1
Affiliations
Review

Protein-protein docking: from interaction to interactome

Ilya A Vakser. Biophys J. .

Abstract

The protein-protein docking problem is one of the focal points of activity in computational biophysics and structural biology. The three-dimensional structure of a protein-protein complex, generally, is more difficult to determine experimentally than the structure of an individual protein. Adequate computational techniques to model protein interactions are important because of the growing number of known protein structures, particularly in the context of structural genomics. Docking offers tools for fundamental studies of protein interactions and provides a structural basis for drug design. Protein-protein docking is the prediction of the structure of the complex, given the structures of the individual proteins. In the heart of the docking methodology is the notion of steric and physicochemical complementarity at the protein-protein interface. Originally, mostly high-resolution, experimentally determined (primarily by x-ray crystallography) protein structures were considered for docking. However, more recently, the focus has been shifting toward lower-resolution modeled structures. Docking approaches have to deal with the conformational changes between unbound and bound structures, as well as the inaccuracies of the interacting modeled structures, often in a high-throughput mode needed for modeling of large networks of protein interactions. The growing number of docking developers is engaged in the community-wide assessments of predictive methodologies. The development of more powerful and adequate docking approaches is facilitated by rapidly expanding information and data resources, growing computational capabilities, and a deeper understanding of the fundamental principles of protein interactions.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The general scheme of protein docking methodology development. The scan (global search for complementarity) is performed on a simplified/coarse-grained representation of proteins (e.g., digitized on a grid, or discretized/approximated in other ways). The scan can be explicit (free) or based on similarity to known cocrystallized complexes (comparative). The refinement is supposed to bring back all or some structural resolution lost in the coarse-graining (e.g., by gradual transition from s smoothed intermolecular energy landscape to the one based on a physical force field, while tracking the position of the global minimum). The validity of the approach is determined by systematic benchmarking on representative sets of structures. To see this figure in color, go online.
Figure 2
Figure 2
Structures with the increasing level of inaccuracy. The model structures (cyan) are overlapped with the x-ray structure (light brown). To see this figure in color, go online.
Figure 3
Figure 3
Structural similarity of the binding modes versus structural similarity of the interacting proteins. The structural similarity of the binding modes is described by interaction RMSD (47). The structural similarity of the interacting proteins is described by min TM-score—the lowest of the two components protein TM-scores (62). The sharp transition to small interaction RMSD occurs at the 0.4 value of structural similarity. To see this figure in color, go online.
Figure 4
Figure 4
Benchmarking of template-based docking. The distribution of predicted complexes accuracies is shown relative to the cocrystallized structure. The benchmarking of PDB complexes released in 2009–2011 was based on template structures from 2008 and earlier. In 36% of the complexes, the predicted structure is close to the native (interface RMSD <5 Å). To see this figure in color, go online.
Figure 5
Figure 5
Structural coverage of protein interactions for five genomes with the largest number of known interactions. Complexes with the x-ray structure are in red, complexes with a sequence template are in green, and complexes for which the structure of the monomers is known are in blue—structural templates are found for ∼100% of such complexes. >1/3 of these templates are estimated to be correct (Fig. 4). To see this figure in color, go online.
Figure 6
Figure 6
Example of docking decoys. Matches represented by the ligand’s center of mass are shown for 1bui enzyme-substrate complex. The receptor (in green) and the ligand (in cyan) are shown in cocrystallized configuration. The native match is in yellow, 10 near-native matches are in red, and 100 nonnative matches are in blue. To see this figure in color, go online.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Platzer K.E.B., Momany F.A., Scheraga H.A. Conformational energy calculations of enzyme-substrate interactions. II. Computation of the binding energy for substrates in the active site of alpha-chymotrypsin. Int. J. Pept. Protein Res. 1972;4:201–219. - PubMed
    1. Pincus M.R., Zimmerman S.S., Scheraga H.A. Prediction of three-dimensional structures of enzyme-substrate and enzyme-inhibitor complexes of lysozyme. Proc. Natl. Acad. Sci. USA. 1976;73:4261–4265. - PMC - PubMed
    1. Wodak S.Y., Liu M.Y., Wyckoff H.W. The structure of cytidilyl(2′,5′)adenosine when bound to pancreatic ribonuclease S. J. Mol. Biol. 1977;116:855–875. - PubMed
    1. Pincus M.R., Scheraga H.A. Conformational energy calculations of enzyme-substrate and enzyme-inhibitor complexes of lysozyme. 2. Calculation of the structures of complexes with flexible enzyme. Macromolecules. 1979;12:633–644.
    1. Wodak S.J., Janin J. Computer analysis of protein-protein interaction. J. Mol. Biol. 1978;124:323–342. - PubMed

Publication types

LinkOut - more resources