Are mixed explicit/implicit solvation models reliable for studying phosphate hydrolysis? A comparative study of continuum, explicit and mixed solvation models.
Phosphate hydrolysis is ubiquitous in biology. However, despite intensive research on this class of reactions, the precise nature of the reaction mechanism remains controversial. In this work, we have examined the hydrolysis of three homologous phosphate diesters. The solvation free energy was simulated by means of either an implicit solvation model (COSMO), hybrid quantum mechanical / molecular mechanical free energy perturbation (QM/MM-FEP) or a mixed solvation model in which N water molecules were explicitly included in the ab initio description of the reacting system (where N=1-3), with the remainder of the solvent being implicitly modelled as a continuum. Here, both COSMO and QM/MM-FEP reproduce Delta Gobs within an error of about 2kcal/mol. However, we demonstrate that in order to obtain any form of reliable results from a mixed model, it is essential to carefully select the explicit water molecules from short QM/MM runs that act as a model for the true infinite system. Additionally, the mixed models tend to be increasingly inaccurate the more explicit water molecules are placed into the system. Thus, our analysis indicates that this approach provides an unreliable way for modelling phosphate hydrolysis in solution.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- Computational Research Division
- DOE Contract Number:
- DE-AC02-05CH11231
- OSTI ID:
- 962213
- Report Number(s):
- LBNL-1984E; TRN: US200915%%423
- Journal Information:
- Chemical Physics and Physical Chemistry, Vol. 10
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
71 CLASSICAL AND QUANTUM MECHANICS
GENERAL PHYSICS
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
BIOLOGY
FREE ENERGY
HYDROLYSIS
PHOSPHATES
REACTION KINETICS
SIMULATION
SOLVATION
SOLVENTS
UNIVERSE
WATER
phosphate hydrolysis reaction mechanism ? mixed solvation model implicit solvation model ? QM/MM