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CRK: An evolutionary approach for distinguishing biologically relevant interfaces from crystal contacts
Author(s) -
Schärer Martin A.,
Grütter Markus G.,
Capitani Guido
Publication year - 2010
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22787
Subject(s) - adapter molecule crk , coding (social sciences) , interface (matter) , computer science , computational biology , biological system , set (abstract data type) , chemistry , signal transducing adaptor protein , biology , mathematics , molecule , biochemistry , gene , programming language , statistics , gibbs isotherm , organic chemistry
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 (ω) 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. Proteins 2010. © 2010 Wiley‐Liss, Inc.