title: Semiempirical quantum mechanical method PM6-DH2X describes the geometry and energetics of CK2-inhibitor complexes involving halogen bonds well, while the empirical potential fails.
abstract: In the present study, we have investigated complexes of CK2 protein kinase with halogenated inhibitors by means of the advanced semiempirical quantum mechanical (SQM) PM6 method (called PM6-DH2X), which describes various types of noncovalent interactions including halogen bonding well. The PM6-DH2X method provides reliable geometries of those CK2 protein kinase-inhibitor complexes involving halogen bonds that agree well with the X-ray crystal structures. When the Amber empirical potential is applied, this agreement becomes considerably worse. Similarly, the binding free energies determined by the PM6-DH2X SQM method are much closer to the experimental inhibition constants than those based on the Amber empirical potential.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Dobes
authors.forename: Jan
authors.initials: J
authors.lastname: Rezác
authors.forename: Jindrich
authors.initials: J
authors.lastname: Fanfrlík
authors.forename: Michal
authors.initials: M
authors.lastname: Otyepka
authors.forename: Pavel
authors.initials: P
authors.lastname: Hobza
mesh_terms: D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D054879:Halogenation; D006219:Halogens / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D004791:Enzyme Inhibitors; D006219:Halogens; D047390:Casein Kinase II