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Title: Proton and hydride transfers in solution: hybrid QMmm/MM free energy perturbation study

Abstract

A hybrid quantum and molecular mechanical (QM/MM) free energy perturbation (FEP) method is implemented in the context of molecular dynamics (MD). The semiempirical quantum mechanical (QM) Hamiltonian (Austin Model 1) represents solute molecules, and the molecular mechanical (MM) CHARMM force field describes the water solvent. The QM/MM FEP method is used to calculate the free energy changes in aqueous solution for (1) a proton transfer from methanol to imidazole and (2) a hydride transfer from methoxide to nicotinamide. The QM/MM interaction energies between the solute and solvent arc calibrated to emulate the solute-solvent interaction energies determined at the Hartee-Fock 6-31G(d) level of ab initio theory. The free energy changes for the proton and hydride transfers are calculated to be 15.1 and {minus}6.3 kcal/mol, respectively, which compare favorably with the corresponding experimental values of 12.9 and {minus}7.4 kcal/mol. An estimate of the reliability of the calculations is obtained through the computation of the forward (15.1 and {minus}6.3 kcal/mol) and backward ({minus}14.1 and 9.1 kcal/mol)free energy changes. The reasonable correspondence between these two independent calculations suggests that adequate phase space sampling is obtained along the reaction pathways chosen to transform the proton and hydride systems between their respective reactant and product states.

Authors:
 [1];  [2];  [3]
  1. Yale Univ., New Haven, CT (United States). Gibbs Lab.
  2. Argonne National Lab., IL (United States)
  3. Maryland University, Baltimore, MD (United States). School of Pharmacy
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE, Washington, DC (United States)
OSTI Identifier:
207038
Report Number(s):
ANL/CMB/PP-87155
ON: DE96007480
DOE Contract Number:  
W-31109-ENG-38
Resource Type:
Technical Report
Resource Relation:
Other Information: PBD: [1996]
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; 40 CHEMISTRY; NICOTINAMIDE; ELECTRON TRANSFER; METHANOL; OXIDOREDUCTASES; BIOCHEMICAL REACTION KINETICS; QUANTUM MECHANICS; FREE ENERGY; IMIDAZOLES; SOLVATION; HAMILTONIANS; PHYSICAL CHEMISTRY

Citation Formats

Ho, L Lawrence, Argonne National Lab., IL, Bash, P A, and Kerell, Jr, A D. Proton and hydride transfers in solution: hybrid QMmm/MM free energy perturbation study. United States: N. p., 1996. Web. doi:10.2172/207038.
Ho, L Lawrence, Argonne National Lab., IL, Bash, P A, & Kerell, Jr, A D. Proton and hydride transfers in solution: hybrid QMmm/MM free energy perturbation study. United States. https://doi.org/10.2172/207038
Ho, L Lawrence, Argonne National Lab., IL, Bash, P A, and Kerell, Jr, A D. 1996. "Proton and hydride transfers in solution: hybrid QMmm/MM free energy perturbation study". United States. https://doi.org/10.2172/207038. https://www.osti.gov/servlets/purl/207038.
@article{osti_207038,
title = {Proton and hydride transfers in solution: hybrid QMmm/MM free energy perturbation study},
author = {Ho, L Lawrence and Argonne National Lab., IL and Bash, P A and Kerell, Jr, A D},
abstractNote = {A hybrid quantum and molecular mechanical (QM/MM) free energy perturbation (FEP) method is implemented in the context of molecular dynamics (MD). The semiempirical quantum mechanical (QM) Hamiltonian (Austin Model 1) represents solute molecules, and the molecular mechanical (MM) CHARMM force field describes the water solvent. The QM/MM FEP method is used to calculate the free energy changes in aqueous solution for (1) a proton transfer from methanol to imidazole and (2) a hydride transfer from methoxide to nicotinamide. The QM/MM interaction energies between the solute and solvent arc calibrated to emulate the solute-solvent interaction energies determined at the Hartee-Fock 6-31G(d) level of ab initio theory. The free energy changes for the proton and hydride transfers are calculated to be 15.1 and {minus}6.3 kcal/mol, respectively, which compare favorably with the corresponding experimental values of 12.9 and {minus}7.4 kcal/mol. An estimate of the reliability of the calculations is obtained through the computation of the forward (15.1 and {minus}6.3 kcal/mol) and backward ({minus}14.1 and 9.1 kcal/mol)free energy changes. The reasonable correspondence between these two independent calculations suggests that adequate phase space sampling is obtained along the reaction pathways chosen to transform the proton and hydride systems between their respective reactant and product states.},
doi = {10.2172/207038},
url = {https://www.osti.gov/biblio/207038}, journal = {},
number = ,
volume = ,
place = {United States},
year = {Fri Mar 01 00:00:00 EST 1996},
month = {Fri Mar 01 00:00:00 EST 1996}
}