Abstract
BackgroundThe physical interactions between proteins constitute the basis of protein quaternary structures. They dominate many biological processes in living cells. Deciphering the structural features of interacting proteins is essential to understand their cellular functions. Similar to the space of protein tertiary structures in which discrete patterns are clearly observed on fold or sub-fold motif levels, it has been found that the space of protein quaternary structures is highly degenerate due to the packing of compact secondary structure elements at interfaces. Therefore, it is necessary to further decompose the protein quaternary structural space into a more local representation.ResultsHere we constructed an interface fragment pair library from the current structure database of protein complexes. After structural-based clustering, we found that more than 90% of these interface fragment pairs can be represented by a limited number of highly abundant motifs. These motifs were further used to guide complex assembly. A large-scale benchmark test shows that the native-like binding is highly likely in the structural ensemble of modeled protein complexes that were built through the library.ConclusionsOur study therefore presents supportive evidences that the space of protein quaternary structures can be represented by the combination of a small set of secondary-structure-based packing at binding interfaces. Finally, after future improvements such as adding sequence profiles, we expect this new library will be useful to predict structures of unknown protein-protein interactions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-014-0437-4) contains supplementary material, which is available to authorized users.
Highlights
The physical interactions between proteins constitute the basis of protein quaternary structures
Our study indicates that the structural space of protein-protein interactions (PPI) can be decomposed by a limited number of interacting fragments
Similar to the space of protein tertiary structures in which discrete patterns are clearly observed on fold and sub-fold motif levels, it has been found that the space of protein quaternary structures is highly degenerate due to the packing of compact secondary structure elements at interfaces
Summary
The physical interactions between proteins constitute the basis of protein quaternary structures They dominate many biological processes in living cells. Traditional docking methods only rely on the geometric and chemical-physical complementarity of modeled protein surfaces [9,10,11] These methods (template-free methods) explore all possible binding modes of two proteins without a priori knowledge of their complex structures. A number of recent studies have used structurally characterized complexes as templates to construct models of unknown PPI [12,13,14,15,16,17] As template-free methods are limited by the ability of sampling the entire conformational space, template-based methods are facing difficulties with limited number of complex structures in current Protein Data Bank (PDB). Considering the remarkable success of fragment-based methods in predicting protein tertiary structures [21], it is reasonable to anticipate that
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