Artificial proteins as allosteric modulators of PDZ3 and SH3 in two-domain constructs: A computational characterization of novel chimeric proteins.
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.
Institute of Organic Chemistry and Biochemistry ASCR, v.v.i, Flemingovo náměstí 2, Prague 6, 166 10, Czech Republic.
Palani
P
Kirubakaran
Institute of Organic Chemistry and Biochemistry ASCR, v.v.i, Flemingovo náměstí 2, Prague 6, 166 10, Czech Republic.
Lucie
L
Pfeiferová
Institute of Organic Chemistry and Biochemistry ASCR, v.v.i, Flemingovo náměstí 2, Prague 6, 166 10, Czech Republic.|Institute of Physiology ASCR, v.v.i, Videnska 1083, 14220 Prague 4, Czech Republic.
Kristýna
K
Boušová
Institute of Organic Chemistry and Biochemistry ASCR, v.v.i, Flemingovo náměstí 2, Prague 6, 166 10, Czech Republic.
Lucie
L
Bednarova
Institute of Physiology ASCR, v.v.i, Videnska 1083, 14220 Prague 4, Czech Republic.
Veronika
V
Obšilová
Institute of Organic Chemistry and Biochemistry ASCR, v.v.i, Flemingovo náměstí 2, Prague 6, 166 10, Czech Republic. jiri.vondrasek@uochb.cas.cz.
Jiří
J
Vondrášek
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D008024:Ligands; D010455:Peptides; D011993:Recombinant Fusion Proteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein
PDZ3; SH3; Trp-cage; circular dichroism; fusion proteins; molecular dynamics simulation; protein design; two domain proteins