Functional Classification Of Protein Complexes

Question

[Reyhaneh]

Hi;

My main aim is to compare PDB protein complexes based on their functions. having different protein complexes I can group them based on their function. Are there any datasets which classifies PDB protein complexes based on their function?

I have been looking at GO terms but my problem is that Go terms are defined for each specific chain in a complex and I am not able to use that to give a clear functional comparison between protein complexes .

Do you have any suggestions?

Thanks in advance;

Reyhaneh

Answer 1

[Alastair Kerr]

Have you looked at Gene3D and Superfamily? Both are based on PDB.

Blurb on Gene3D [?]The Gene3D database is a large collection of CATH protein domain assignments for ENSEMBL genomes and Uniprot sequences Hide.

Proteins are generally composed of one or more functional regions, commonly termed domains. Domain annotation resources such as CATH provide curated domain assignments and a grouping of domains into families sharing evidence of homology (superfamilies). Although not a one to one relationship, a given domain superfamily will have a limited number of functions that its members fulfill in the whole-protein context. The combination of domains from different superfamilies gives rise to novel protein functions. Therefore, identifying the domains in a protein can give useful insights into protein function.

Finer grained groupings of superfamilies based on function (FunFams), and structure (SCs) are also provided. Gene3D is also unique in that it provides example of nested domains, where a given domain may have been inserted into another during evolution. [?]

Blurb on Superfamily [?] SUPERFAMILY is a database of structural and functional annotation for all proteins and genomes.

The SUPERFAMILY annotation is based on a collection of hidden Markov models, which represent structural protein domains at the SCOP superfamily level. A superfamily groups together domains which have an evolutionary relationship. The annotation is produced by scanning protein sequences from over 1,700 completely sequenced genomes against the hidden Markov models.[?]

Gene3D is based on CATH

[?] CATH is a manually curated classification of protein domain structures. Each protein has been chopped into structural domains and assigned into homologous superfamilies (groups of domains that are related by evolution). This classification procedure uses a combination of automated and manual techniques which include computational algorithms, empirical and statistical evidence, literature review and expert analysis. [?]

Superfamily is based on SCOP

[?] The SCOP database, created by manual inspection and abetted by a battery of automated methods, aims to provide a detailed and comprehensive description of the structural and evolutionary relationships between all proteins whose structure is known. As such, it provides a broad survey of all known protein folds, detailed information about the close relatives of any particular protein, and a framework for future research and classification.[?]

[Reyhaneh]

Thank you for this. But using this database how are you able to get all the PDB structures that have the same function as "2fcw" for example?

[Alastair Kerr]

Gene3d - get protein using id 2fcw. That give you 2 genes LRPAP1 and LDLR. Note the link to the CATH Homologous Superfamily 1.20.81.10. Using this gives you receptor associated protein group. You can also use the Interpro domains (e.g. PFAM) to find similar function. Search these on Interpro or even Biomart if you wished to find all linked proteins. This is just a quick example, the are tutorials and help documentation associated with each site.

Answer 2

[Fidel]

You can retrieve the GO term of each chain and then find the lowest common ancestor of such terms for the complex. This will give you the basis to classify you PDB complexes.

You can find here examples on how to find the lowest common ancestor.