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Artificial proteins as allosteric modulators of PDZ3 and SH3 in two‐domain constructs: A computational characterization of novel chimeric proteins
Author(s) -
Kirubakaran Palani,
Pfeiferová Lucie,
Boušová Kristýna,
Bednarova Lucie,
Obšilová Veronika,
Vondrášek Jiří
Publication year - 2016
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.25082
Subject(s) - allosteric regulation , molecular dynamics , fusion protein , computational biology , biomolecule , domain (mathematical analysis) , protein domain , sh3 domain , biophysics , chemistry , biology , biochemistry , mathematics , computational chemistry , recombinant dna , gene , proto oncogene tyrosine protein kinase src , mathematical analysis , kinase , enzyme
Artificial multidomain proteins with enhanced structural and functional properties can be utilized in a broad spectrum of applications. The design of chimeric fusion proteins utilizing protein domains or one‐domain miniproteins as building blocks is an important advancement for the creation of new biomolecules for biotechnology and medical applications. However, computational studies to describe in detail the dynamics and geometry properties of two‐domain constructs made from structurally and functionally different proteins are lacking. Here, we tested an in silico design strategy using all‐atom explicit solvent molecular dynamics simulations. The well‐characterized PDZ3 and SH3 domains of human zonula occludens (ZO‐1) (3TSZ), along with 5 artificial domains and 2 types of molecular linkers, were selected to construct chimeric two‐domain molecules. The influence of the artificial domains on the structure and dynamics of the PDZ3 and SH3 domains was determined using a range of analyses. We conclude that the artificial domains can function as allosteric modulators of the PDZ3 and SH3 domains. Proteins 2016; 84:1358–1374. © 2016 Wiley Periodicals, Inc.