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Decomposing the space of protein quaternary structures with the interface fragment pair library.

Xie ZR, Chen J, Zhao Y, Wu Y - BMC Bioinformatics (2015)

Bottom Line: 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.Our 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems and Computational Biology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY, 10461, USA. Zhong-Ru.Xie@einstein.yu.edu.

ABSTRACT

Background: The 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.

Results: Here 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.

Conclusions: Our 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.

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We collected information of interface fragment pairs from a database of interacting protein domains. For a pair of two protein domains that form physical contacts (a), an interface fragment pair is defined as a pair of 9-amino-acid-long fragments, in which their centered residues form at least one atomic contact (b).
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Fig1: We collected information of interface fragment pairs from a database of interacting protein domains. For a pair of two protein domains that form physical contacts (a), an interface fragment pair is defined as a pair of 9-amino-acid-long fragments, in which their centered residues form at least one atomic contact (b).

Mentions: Here we constructed an interface fragment pair library from the current structure database of protein complexes. For any dimeric complex in the database, an interface fragment pair is defined as a pair of 9-residue-long fragments from each side of the complex. Both residues in the middle of these two fragments are located at the dimer interface and form contacts at the atomic level (Figure 1). All pairs of fragments from all complexes in the database were recorded by the coordinates of their C-α atoms. Pairs with similar packing geometry were then clustered together. Only clusters that contain a relatively large number of fragment pairs were selected. The library consists of representative structures of all these most abundant clusters. We further used the library to guide complex assembly by aligning all structurally similar fragments from the two monomers to the corresponding fragment pair in the library. Through the test on a large-scale protein docking benchmark [32], we found that native-like quaternary structures were among all assembled complex models with a successful rate of more than 90%. Our study indicates that the structural space of PPI can be decomposed by a limited number of interacting fragments. Furthermore, after adding more features such as sequence profiles in the future, we expect this new library will be proved useful in predicting quaternary structures of unknown PPI.Figure 1


Decomposing the space of protein quaternary structures with the interface fragment pair library.

Xie ZR, Chen J, Zhao Y, Wu Y - BMC Bioinformatics (2015)

We collected information of interface fragment pairs from a database of interacting protein domains. For a pair of two protein domains that form physical contacts (a), an interface fragment pair is defined as a pair of 9-amino-acid-long fragments, in which their centered residues form at least one atomic contact (b).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4384354&req=5

Fig1: We collected information of interface fragment pairs from a database of interacting protein domains. For a pair of two protein domains that form physical contacts (a), an interface fragment pair is defined as a pair of 9-amino-acid-long fragments, in which their centered residues form at least one atomic contact (b).
Mentions: Here we constructed an interface fragment pair library from the current structure database of protein complexes. For any dimeric complex in the database, an interface fragment pair is defined as a pair of 9-residue-long fragments from each side of the complex. Both residues in the middle of these two fragments are located at the dimer interface and form contacts at the atomic level (Figure 1). All pairs of fragments from all complexes in the database were recorded by the coordinates of their C-α atoms. Pairs with similar packing geometry were then clustered together. Only clusters that contain a relatively large number of fragment pairs were selected. The library consists of representative structures of all these most abundant clusters. We further used the library to guide complex assembly by aligning all structurally similar fragments from the two monomers to the corresponding fragment pair in the library. Through the test on a large-scale protein docking benchmark [32], we found that native-like quaternary structures were among all assembled complex models with a successful rate of more than 90%. Our study indicates that the structural space of PPI can be decomposed by a limited number of interacting fragments. Furthermore, after adding more features such as sequence profiles in the future, we expect this new library will be proved useful in predicting quaternary structures of unknown PPI.Figure 1

Bottom Line: 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.Our 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems and Computational Biology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY, 10461, USA. Zhong-Ru.Xie@einstein.yu.edu.

ABSTRACT

Background: The 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.

Results: Here 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.

Conclusions: Our 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.

Show MeSH
Related in: MedlinePlus