title: Refinement of X-ray data on dual cosubstrate specificity of CK2 kinase by free energy calculations based on molecular dynamics simulation.
abstract: 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.
authors.affiliation: Warsaw University, Institute of Experimental Physics, Department of Biophysics, Poland. piosto@icm.edu.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Setny
authors.forename: Maciej
authors.initials: M
authors.lastname: Geller
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D001665:Binding Sites; D047390:Casein Kinase II / Q000737:chemistry*; D020134:Catalytic Domain; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D018360:Crystallography, X-Ray / Q000379:methods*; D006160:Guanosine Triphosphate / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D010710:Phosphates / Q000737:chemistry; D011485:Protein Binding; D012984:Software; D013379:Substrate Specificity; D013816:Thermodynamics; D014867:Water; D003313:Zea mays / Q000201:enzymology
chemical_list: D008024:Ligands; D010710:Phosphates; D014867:Water; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D047390:Casein Kinase II