Processing multimode binding situations in simulation-based prediction of ligand-macromolecule affinities.

ABSTRACT: The linear response (LR) approximation and similar approaches belong to practical methods for estimation of ligand-receptor binding affinities. The approaches correlate experimental binding affinities with the changes upon binding of the ligand electrostatic and van der Waals energies and of solvation characteristics. These attributes are expressed as ensemble averages that are obtained by conformational sampling of the protein-ligand complex and of the free ligand by molecular dynamics or Monte Carlo simulations. We observed that outliers in the LR correlations occasionally exhibit major conformational changes of the complex during sampling. We treated the situation as a multimode binding case, for which the observed association constant is the sum of the partial association constants of

SUBMITTER: Khandelwal A 

PROVIDER: S-EPMC2896054 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature