Direct calculation of the binding free energies of FKBP ligands. Journal Article uri icon



  • Direct calculations of the absolute free energies of binding for eight ligands to FKBP protein were performed using the Fujitsu BioServer massively parallel computer. Using the latest version of the general assisted model building with energy refinement (AMBER) force field for ligand model parameters and the Bennett acceptance ratio for computing free-energy differences, we obtained an excellent linear fit between the calculated and experimental binding free energies. The rms error from a linear fit is 0.4 kcal/mol for eight ligand complexes. In comparison with a previous study of the binding energies of these same eight ligand complexes, these results suggest that the use of improved model parameters can lead to more predictive binding estimates, and that these estimates can be obtained with significantly less computer time than previously thought. These findings make such direct methods more attractive for use in rational drug design.

publication date

  • August 22, 2005

has subject area

has restriction

  • closed

Date in CU Experts

  • September 4, 2015 2:15 AM

Full Author List

  • Fujitani H; Tanida Y; Ito M; Jayachandran G; Snow CD; Shirts MR; Sorin EJ; Pande VS

author count

  • 8

Other Profiles

International Standard Serial Number (ISSN)

  • 0021-9606

Additional Document Info

start page

  • 084108


  • 123


  • 8