Molecular dynamics and free energy perturbation calculations on fluorocarbons and aspartyl protease inhibitors
Molecular dynamics (MD) simulations of pure tetrafluoromethane and trifluoromethane were performed to determine the van der Waals parameters R[sup *] and [epsilon] for fluorine and for the hydrogen of trifluoromethane. The best values of R[sup *] and [epsilon] for fluorine were determined to be 1.75 [angstrom] and 0.061 kcal/mole. For the hydrogen, the optimal R[sup *] and [epsilon] were determined to be 1.21 [angstrom] and 0.015 kcal/mole. The relative free energies of aqueous solvation of several fluorinated derivatives of methane were calculated using the FEP method. The calculations duplicated the experimental free energies relatively well, but the calculation of the bond-potential of mean force (bond-PMF) contribution was necessary in order to get the most satisfactory agreement with experiment. In addition, results of an ethanol-to-ethane perturbation in aqueous solution show that the bond-PMF contribution is important even for FEP calculations not involving large changes in size if the length of a bond is changed during the perturbation. MD simulations were run to determine the structure of the waters solvating fluoromethane, trifluoromethane, and tetrafluoromethane. The calculated radical distribution functions and water orientations suggest that, on average, there is one water-fluorine hydrogen bond in the case of fluoromethane. In contrast, there is no evidence of water-flourine hydrogen-bonding in the cases of trifluoromethane or tetrafluoromethane. These results suggest that the greater aqueous solubility of fluromethane relative to trifluoromethane is largely due to the poorer quality of the water-fluorine electrostatic interactions in trifluoromethane.
- Research Organization:
- California Univ., San Francisco, CA (United States)
- OSTI ID:
- 7275046
- Resource Relation:
- Other Information: Thesis (Ph.D.)
- Country of Publication:
- United States
- Language:
- English
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