Počet záznamů: 1

Transferable scoring function based on semiempirical quantum mechanical PM6-DH2 method: CDK2 with 15 structurally diverse inhibitors

  1. 1.
    0360708 - UOCHB-X 2012 RIV NL eng J - Článek v odborném periodiku
    Dobeš, Petr - Fanfrlík, Jindřich - Řezáč, Jan - Otyepka, M. - Hobza, Pavel
    Transferable scoring function based on semiempirical quantum mechanical PM6-DH2 method: CDK2 with 15 structurally diverse inhibitors.
    Journal of Computer-Aided Molecular Design. Roč. 25, č. 3 (2011), s. 223-235 ISSN 0920-654X
    Grant CEP: GA MŠk LC512; GA ČR GAP208/11/0295
    Grant ostatní:European Social Fund(XE) CZ.1.05/2.1.00/03.0058
    Výzkumný záměr: CEZ:AV0Z40550506
    Klíčová slova: CDK2 * semiempirical quantum mechanical method PM6-DH2 * drug design
    Kód oboru RIV: CF - Fyzikální chemie a teoretická chemie
    Impakt faktor: 3.386, rok: 2011

    Abstract A semiempirical quantum mechanical PM6-DH2 method accurately covering the dispersion interaction and H-bonding was used to score fifteen structurally diverse CDK2 inhibitors. The geometries of all the complexes were taken from the X-ray structures and were reoptimised by the PM6-DH2 method in continuum water. The total scoring function was constructed as an estimate of the binding free energy, i.e., as a sum of the interaction enthalpy, interaction entropy and the corrections for the inhibitor desolvation and deformation energies. The applied scoring function contains a clear thermodynamical terms and does not involve any adjustable empirical parameter. The best correlations with the experimental inhibition constants (ln Ki) were found for bare interaction enthalpy (r2 = 0.87) and interaction enthalpy corrected for ligand desolvation and deformation energies (r2 = 0.77); when the entropic term was considered, however, the correlation becomes worse but still acceptable.
    Trvalý link: http://hdl.handle.net/11104/0198195