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Keywords:

  • computational docking;
  • prediction of free energy;
  • force fields;
  • desolvation models;
  • computer-aided drug design;
  • AutoDock4

Abstract

The authors describe the development and testing of a semiempirical free energy force field for use in AutoDock4 and similar grid-based docking methods. The force field is based on a comprehensive thermodynamic model that allows incorporation of intramolecular energies into the predicted free energy of binding. It also incorporates a charge-based method for evaluation of desolvation designed to use a typical set of atom types. The method has been calibrated on a set of 188 diverse protein–ligand complexes of known structure and binding energy, and tested on a set of 100 complexes of ligands with retroviral proteases. The force field shows improvement in redocking simulations over the previous AutoDock3 force field. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007