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CRK: an evolutionary approach for distinguishing biologically relevant interfaces from crystal contacts


Schärer, M A; Grütter, M G; Capitani, G (2010). CRK: an evolutionary approach for distinguishing biologically relevant interfaces from crystal contacts. Proteins, 78(12):2707-2713.

Abstract

Protein crystals contain two different types of interfaces: biologically relevant ones, observed in protein-protein complexes and oligomeric proteins, and nonspecific ones, corresponding to crystal lattice contacts. Because of the increasing complexity of the objects being tackled in structural biology, distinguishing biological contacts from crystal contacts is not always a trivial task and can lead to wrong interpretation of macromolecular structures. We devised an approach (CRK, core-rim K(a)/K(s) ratio) for distinguishing biologically relevant interfaces from nonspecific ones. Given a protein-protein interface, CRK finds a set of homologs to the sequences of the proteins involved in the interface, retrieves and aligns the corresponding coding sequences, on which it carries out a residue-by-residue K(a)/K(s) ratio (omega) calculation. It divides interface residues into a "rim" and a "core" set and analyzes the selection pressure on the residues belonging to the two sets. We developed and tested CRK on different datasets and test cases, consisting of biologically relevant contacts, nonspecific ones or of both types. The method proves very effective in distinguishing the two categories of interfaces, with an overall accuracy rate of 84%. As it relies on different principles when compared with existing tools, CRK is optimally suited to be used in combination with them. In addition, CRK has potential applications in the validation of structures of oligomeric proteins and protein complexes.

Abstract

Protein crystals contain two different types of interfaces: biologically relevant ones, observed in protein-protein complexes and oligomeric proteins, and nonspecific ones, corresponding to crystal lattice contacts. Because of the increasing complexity of the objects being tackled in structural biology, distinguishing biological contacts from crystal contacts is not always a trivial task and can lead to wrong interpretation of macromolecular structures. We devised an approach (CRK, core-rim K(a)/K(s) ratio) for distinguishing biologically relevant interfaces from nonspecific ones. Given a protein-protein interface, CRK finds a set of homologs to the sequences of the proteins involved in the interface, retrieves and aligns the corresponding coding sequences, on which it carries out a residue-by-residue K(a)/K(s) ratio (omega) calculation. It divides interface residues into a "rim" and a "core" set and analyzes the selection pressure on the residues belonging to the two sets. We developed and tested CRK on different datasets and test cases, consisting of biologically relevant contacts, nonspecific ones or of both types. The method proves very effective in distinguishing the two categories of interfaces, with an overall accuracy rate of 84%. As it relies on different principles when compared with existing tools, CRK is optimally suited to be used in combination with them. In addition, CRK has potential applications in the validation of structures of oligomeric proteins and protein complexes.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2010
Deposited On:09 Nov 2010 16:04
Last Modified:05 Apr 2016 14:15
Publisher:Wiley-Blackwell
ISSN:0887-3585
Publisher DOI:https://doi.org/10.1002/prot.22787
PubMed ID:20589644

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