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protein evolution

Tuesday 24 October 2006

Assessing protein modularity is important to understand protein evolution. Still the question of the existence of a sub-domain modular architecture remains.

Authors propose a graph-theory approach with significance and power testing to identify modules in protein structures. In the first step, clusters are determined by optimizing the partition that maximizes the modularity score. Second, each cluster is tested for significance. Significant clusters are referred to as modules. Evolutionary modules are identified by analyzing homologous structures. Dynamic modules are inferred from sets of snapshots of molecular simulations.

A domain compartmentalization can be found and described in correlation space. To our knowledge, there is no other method attempting to identify sub-domain architecture from the correlation among residues.

Most attempts made focus on sequence motifs of protein-protein interactions, binding sites, or sequence conservancy. They were able to describe functional/structural sub-domain architecture related to key residues for starch cleavage, calcium, and chloride binding sites in the α-amylase, and sterol opening-defining modules and disease-related residues in the NPC1.

They described the evolutionary sub-domain architecture of the α-amylase catalytic domain, identifying the already reported minimum functional TIM barrel.

See also

- protein modularity

Open References

- Defining structural and evolutionary modules in proteins: a community detection approach to explore sub-domain architecture. Hleap JS, Susko E, Blouin C.
BMC Struct Biol. 2013 Oct 16;13:20. doi : 10.1186/1472-6807-13-20
PMID: 24131821 Free

Paywall References

- Pal C, Papp B, Lercher MJ. An integrated view of protein evolution. Nat Rev Genet. 2006 May;7(5):337-48. PMID: 16619049

- Rocha EP. The quest for the universals of protein evolution. Trends Genet. 2006 Aug;22(8):412-6. PMID: 16808987