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Simulation reveals two major docking pathways between the hexapeptide GDYMNM and the catalytic domain of the insulin receptor protein kinase
Author(s) -
Huang Zunnan,
Wong Chung F.
Publication year - 2012
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.24116
Subject(s) - docking (animal) , chemistry , macromolecular docking , insulin receptor , biochemistry , peptide , tyrosine , biophysics , receptor tyrosine kinase , kinetics , microbiology and biotechnology , receptor , insulin , stereochemistry , protein structure , biology , insulin resistance , nursing , endocrinology , physics , quantum mechanics , medicine
Extending a previous mining‐minima approach to identifying the docking pathways between the hexapeptide GDYMNM and the catalytic domain of the insulin receptor tyrosine kinase (IRK), we found two major docking pathways connecting the binding pocket and the surface of the protein. One pathway was more likely to lead to phosphate transfer from ATP to the peptide as the distance between the γ‐phosphate of ATP and the hydroxyl oxygen of the target tyrosine approached one that could facilitate reaction. The movement of the peptide along the pathways was found to couple with residues in the activation loop of the protein. Although these residues might not affect binding affinity, they might influence the kinetics of peptide entrance and release. Proteins 2012; © 2012 Wiley Periodicals, Inc.