Calculation of binding energy differences for receptor–ligand systems using the Poisson-Boltzmann method
✍ Scribed by Jian Shen; Florante A. Quiocho
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 352 KB
- Volume
- 16
- Category
- Article
- ISSN
- 0192-8651
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✦ Synopsis
An approach using the finite difference solution of the Poisson-Boltzmann equation to estimate binding free energy changes for two receptor-ligand systems, arabinose binding protein and sulfate binding protein, is presented. The eight calculated binding free energy changes agree with experiment, showing a correlation coefficient of 0.92 and energy deviations of 1 kcal/mol or less. More importantly, the decomposition of solvation and assembly energies in this approach provides an understanding of binding mechanisms and therefore could suggest directions to alter binding affinities. The method is demonstrated to be useful in analyzing experimental binding structures and predicting binding effects of mutants or modified ligands for macromolecular systems, in which the electrostatic forces dominate the overall interaction and the structural perturbations upon modifications are small. 0 1995 by John Wiley & Sons, Inc.
ing the electrostatic contributions to the hydration free energy of small molecules and ions.' The relative accuracy, inclusion of implicit solvent and ionic strength, as well as computing speed make it possible to use the methods as a tool for estimating rate constants3 and pK, shifts4 in a number of macromolecule systems. However, an unsuccessful application5 suggested that the FDPB method is inaccurate in calculating binding free energy calculation scheme as well as newly developed *Author to whom all correspondence should be addressed at Sterling Winthrop Inc., 1250 S. College Rd., P. 0. Box 5000, T between a ligand and a protein-Using a different Collegeville, PA 19426-0900.