Binding affinity prediction for ligands and receptors forming tautomers and ionization species: inhibition of mitogen-activated protein kinase-activated protein kinase 2 (MK2).

ABSTRACT: Treatment of ionization and tautomerism of ligands and receptors is one of the unresolved issues in structure-based prediction of binding affinities. Our solution utilizes the thermodynamic master equation, expressing the experimentally observed association constant as the sum of products, each valid for a specific ligand-receptor species pair, consisting of the association microconstant and the fractions of the involved ligand and receptor species. The microconstants are characterized by structure-based simulations, which are run for individual species pairs. Here we incorporated the multispecies approach into the QM/MM linear response method and used it for structural correlation of published inhibition data on mitogen-activated protein kinase (MAPK)-activated protein kinase (MK2) by 66

SUBMITTER: Natesan S 

PROVIDER: S-EPMC3315360 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature