HOMCOS: a server to predict interacting protein pairs and interacting sites by homology modeling of complex structures - PubMed (original) (raw)

. 2008 Jul 1;36(Web Server issue):W185-9.

doi: 10.1093/nar/gkn218. Epub 2008 Apr 28.

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HOMCOS: a server to predict interacting protein pairs and interacting sites by homology modeling of complex structures

Naoshi Fukuhara et al. Nucleic Acids Res. 2008.

Abstract

As protein-protein interactions are crucial in most biological processes, it is valuable to understand how and where protein pairs interact. We developed a web server HOMCOS (Homology Modeling of Complex Structure, http://biunit.naist.jp/homcos) to predict interacting protein pairs and interacting sites by homology modeling of complex structures. Our server is capable of three services. The first is modeling heterodimers from two query amino acid sequences posted by users. The server performs BLAST searches to identify homologous templates in the latest representative dataset of heterodimer structures generated from the PQS database. Structure validity is evaluated by the combination of sequence similarity and knowledge-based contact potential energy as previously described. The server generates a sequence-replaced model PDB file and a MODELLER script to build full atomic models of complex structures. The second service is modeling homodimers from one query sequence. The third service is identification of potentially interacting proteins for one query sequence. The server searches the dataset of heterodimer structures for a homologous template, outputs the candidate interacting sequences in the Uniprot database homologous for the interacting partner template proteins. These features are useful for wide range of researchers to predict putative interaction sites and interacting proteins.

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Figures

Figure 1.

Figure 1.

Overview of the procedures for modeling heterodimer structures.

Figure 2.

Figure 2.

Screenshots of the service for modeling heterodimer structures. (A) The title page contains two forms in which a user can input two query protein sequences. (B) A result summarizing two BLAST searches against the heterodimer database. (C) A generated simple sequence-replaced model viewed with the Jmol software.

Figure 3.

Figure 3.

Overview of the procedures for identifying putative interacting proteins.

Figure 4.

Figure 4.

Definition of similarity between heterodimers for the representative heterodimer dataset. Similarity between a dimer of protein A0 and A1 and a dimer of protein B0 and B1 is defined as follows. The sequence similarities S(A0,B0), S(A0,B1), S(A1,B0) and S(A1,B1) are calculated. The value S(A_i_,B_j_) is defined as the sequence similarity between protein A_i_ and protein B_j_. If S(A_i_,B_j_) is the highest of the four similarity values, the corresponding pairs are (A_i_,B_j_) and (A_i′_,B_j ′_) where i′ = (i + 1)%2 and j ′ = (j + 1)%2. The sequence similarity between the two heterodimers is defined as the lower sequence similarity S(A_i′_,B_j ′_) of the two sequence similarities between corresponding proteins S(A_i_,B_j_) and S(A_i′_,B_j ′_). For example, if S(A_1_,B_1_) has the greatest value, the similarity between the dimer is S(A0,B0).

References

    1. Kleanthous C, editor. Protein-Protein Recognition. Oxford: Oxford University Press; 2000.
    1. von Mering C, Krause R, Snel B, Cornell M, Oliver SG, Fields S, Bork P. Comparative assessment of large-scale data sets of protein-protein interactions. Nature. 2002;417:399–403. - PubMed
    1. Deane CM, Salwinski L, Xenarios I, Eisenberg D. Protein interactions: two methods for assessment of the reliability of high throughput observations. Mol. Cell. Prot. 2002;1:349–356. - PubMed
    1. Sprinzak E, Sattath S, Margalit H. How reliable are experimental protein-protein interaction data? J. Mol. Biol. 2003;327:919–923. - PubMed
    1. Berman HM, Henrick K, Nakamura H. Announcing the worldwide Protein Data Bank. Nature Str. Biol. 2003;10:980. - PubMed

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