Improved estimation of ligand-macromolecule binding affinities by linear response approach using a combination of multi-mode MD simulation and QM/MM methods.

ABSTRACT: Structure-based predictions of binding affinities of ligands binding to proteins by coordination bonds with transition metals, covalent bonds, and bonds involving charge re-distributions are hindered by the absence of proper force fields. This shortcoming affects all methods which use force-field-based molecular simulation data on complex formation for affinity predictions. One of the most frequently used methods in this category is the Linear Response (LR) approach of Aquist, correlating binding affinities with van der Waals and electrostatic energies, as extended by Jorgensen's inclusion of solvent-accessible surface areas. All these terms represent the differences, upon binding, in the ensemble averages of pertinent quantities, obtained from molecular dynamics (MD) or Monte Carlo simula

SUBMITTER: Khandelwal A 

PROVIDER: S-EPMC2896052 | biostudies-literature | 2007 Jan-Mar

REPOSITORIES: biostudies-literature