New Coarse Variables for the Accurate Determination of Standard Binding Free Energies

J Chem Theory Comput. 2017 Nov 14;13(11):5173-5178. doi: 10.1021/acs.jctc.7b00791. Epub 2017 Oct 9.


To improve sampling of the configurational entropy change upon protein-ligand binding, we have introduced a new set of coarse variables describing the relative orientation and position of the ligand via a global macromolecular orientational procedure, onto which geometrical restraints are applied. Evaluating the potential of mean force for the different coarse variables, the experimental standard binding free energy for three decapeptides associated with the SH3 domain of the Abl kinase is reproduced quantitatively.

MeSH terms

  • Binding Sites
  • Entropy*
  • Ligands
  • Models, Molecular
  • Protein Binding
  • Thermodynamics
  • src Homology Domains*


  • Ligands