QM/MM linear response method distinguishes ligand affinities for closely related metalloproteins.

ABSTRACT: Design of selective ligands for closely related targets is becoming one of the most important tasks in the drug development. New tools, more precise than fast scoring functions and less demanding than sophisticated Free Energy Perturbation methods, are necessary to help accomplish this goal. The methods of intermediate complexity, characterizing individual contributions to the binding energy, have been an area of intense research in the past few years. Our recently developed quantum mechanical/molecular mechanical (QM/MM) modification of the Linear Response (LR) method describes the binding free energies as the sum of empirically weighted contributions of the QM/MM interaction energies and solvent-accessible surface areas for the time-averaged structures of hydrated complexes, obtained by

SUBMITTER: Khandelwal A 

PROVIDER: S-EPMC2896063 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature