Free energy calculation methods: A theoretical and empirical comparison of numerical errors and a new method qualitative estimates of free energy changes

✍ Scribed by Radmer, Randall J.; Kollman, Peter A.

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 228 KB
• Volume: 18
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/(sici)1096-987x(199705)18:7<902::aid-jcc4>3.0.co;2-v

✦ Synopsis

We present a comparison of four free energy calculation methods: Ž .

Ž . thermodynamic integration TI ; traditional free energy perturbation FEP ;

Ž . Bennett's acceptance ratio method IPS ; and a method that is related to an Ž . implementation of the WHAM method CRS . The theoretical bases of the methods are first described, then calculations of the solvation free energies of methane and ethane are performed to determine the magnitude of the errors for the different methods. We find that the methods give similar errors when many Ž . intermediate states windows are used, but the IPS and CRS methods give smaller errors than the TI and FEP methods when no intermediate states are Ž . used. We also present a new procedure based on the CRS method that uses coordinates from simulations of a set of solutes to calculate the solvation free energies of additional solutes for which no simulations were performed. Ž Solvation free energies for nine solutes methanol, dimethylether, methylamine, methylammonium, dimethylamine, fluoromethane, difluoromethane, . trifluoromethane, and tetrafluoromethane are estimated based only on Ž simulations of set of small hydrophobic solutes including methane, ethane, and