Dataset Information

The interwinding nature of protein-protein interfaces and its implication for protein complex formation.

ABSTRACT:

Motivation

Structural features at protein-protein interfaces can be studied to understand protein-protein interactions. It was noticed that in a dataset of 45 multimeric proteins the interface could either be described as flat against flat or protruding/interwound. In the latter, residues within one chain were surrounded by those in other chains, whereas in the former they were not.

Results

A simple method was developed that could distinguish between these two types with results that matched those made by a human annotator. Applying this automatic method to a large dataset of 888 structures, chains at interfaces were categorized as non-surrounded or surrounded. It was found that the surrounded set had a significantly lower folding tendency using a sequence based measure, than the non-surrounded set. This suggests that before complexation, surrounded chains are relatively unstable and may be involved in 'fly-casting'. This is supported by the finding that terminal regions are overrepresented in the surrounded set.

Availability

http://cib.cf.ocha.ac.jp/DACSIS/.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Yura K

PROVIDER: S-EPMC2778332 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Publications

The interwinding nature of protein-protein interfaces and its implication for protein complex formation.

Yura Kei K Hayward Steven S

Bioinformatics (Oxford, England) 20090929 23

<h4>Motivation</h4>Structural features at protein-protein interfaces can be studied to understand protein-protein interactions. It was noticed that in a dataset of 45 multimeric proteins the interface could either be described as flat against flat or protruding/interwound. In the latter, residues within one chain were surrounded by those in other chains, whereas in the former they were not.<h4>Results</h4>A simple method was developed that could distinguish between these two types with results t ...[more]

PMID: 19789269

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Project description:Many protein-protein interactions (PPIs) are compelling targets for drug discovery, and in a number of cases can be disrupted by small molecules. The main goal of this study is to examine the mechanism of binding site formation in the interface region of proteins that are PPI targets by comparing ligand-free and ligand-bound structures. To avoid any potential bias, we focus on ensembles of ligand-free protein conformations obtained by nuclear magnetic resonance (NMR) techniques and deposited in the Protein Data Bank, rather than on ensembles specifically generated for this study. The measures used for structure comparison are based on detecting binding hot spots, i.e., protein regions that are major contributors to the binding free energy. The main tool of the analysis is computational solvent mapping, which explores the surface of proteins by docking a large number of small "probe" molecules. Although we consider conformational ensembles obtained by NMR techniques, the analysis is independent of the method used for generating the structures. Finding the energetically most important regions, mapping can identify binding site residues using ligand-free models based on NMR data. In addition, the method selects conformations that are similar to some peptide-bound or ligand-bound structure in terms of the properties of the binding site. This agrees with the conformational selection model of molecular recognition, which assumes such pre-existing conformations. The analysis also shows the maximum level of similarity between unbound and bound states that is achieved without any influence from a ligand. Further shift toward the bound structure assumes protein-peptide or protein-ligand interactions, either selecting higher energy conformations that are not part of the NMR ensemble, or leading to induced fit. Thus, forming the sites in protein-protein interfaces that bind peptides and can be targeted by small ligands always includes conformational selection, although other recognition mechanisms may also be involved.

Dataset Information

The interwinding nature of protein-protein interfaces and its implication for protein complex formation.

Motivation

Results

Availability

Supplementary information

Publications

The interwinding nature of protein-protein interfaces and its implication for protein complex formation.

Similar Datasets

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