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Refinement of X‐ray data on dual cosubstrate specificity of CK2 kinase by free energy calculations based on molecular dynamics simulation
Author(s) -
Setny Piotr,
Geller Maciej
Publication year - 2004
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.20350
Subject(s) - molecular dynamics , dual (grammatical number) , dynamics (music) , cofactor , energy (signal processing) , chemistry , computer science , computational chemistry , physics , biochemistry , enzyme , quantum mechanics , art , literature , acoustics
Free energy differences of binding of adenosine triphosphate (ATP) and guanine triphosphate (GTP) to the protein kinase CK2 (casein kinase 2) were calculated, using molecular dynamics (MD) simulations and the thermodynamic cycle approach. Good agreement with experimental data was obtained. Simulations confirm observations based on crystallographic data that specifically interacting water molecules in the binding site region of CK2 kinase play a key role in its ability to use ATP or GTP as equally efficient phosphate donors. We point out that to obtain quantitatively reasonable results, it was necessary to modify original X‐ray data by assuming the presence of an additional water molecule in the CK2 binding site structure with GTP. Proteins 2005. © 2004 Wiley‐Liss, Inc.