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Quantum mechanics/molecular mechanics dual Hamiltonian free energy perturbation

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons58894

Polyak,  Iakov
Research Department Thiel, Max-Planck-Institut für Kohlenforschung, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons58421

Benighaus,  Tobias
Research Department Thiel, Max-Planck-Institut für Kohlenforschung, Max Planck Society;
Lanxess Deutschland GmbH;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons58452

Boulanger,  Eliot
Research Department Thiel, Max-Planck-Institut für Kohlenforschung, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons59045

Thiel,  Walter
Research Department Thiel, Max-Planck-Institut für Kohlenforschung, Max Planck Society;

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Citation

Polyak, I., Benighaus, T., Boulanger, E., & Thiel, W. (2013). Quantum mechanics/molecular mechanics dual Hamiltonian free energy perturbation. The Journal of Chemical Physics, 139, 064105/1-064105/11. doi:10.1063/1.4817402.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0014-A345-6
Abstract
The dual Hamiltonian free energy perturbation (DH-FEP) method is designed for accurate and efficient evaluation of the free energy profile of chemical reactions in quantum mechanical/molecular mechanical (QM/MM) calculations. In contrast to existing QM/MM FEP variants, the QM region is not kept frozen during sampling, but all degrees of freedom except for the reaction coordinate are sampled. In the DH-FEP scheme, the sampling is done by semiempirical QM/MM molecular dynamics (MD), while the perturbation energy differences are evaluated from high-level QM/MM single-point calculations at regular intervals, skipping a pre-defined number of MD sampling steps. After validating our method using an analytic model potential with an exactly known solution, we report a QM/MM DH-FEP study of the enzymatic reaction catalyzed by chorismate mutase. We suggest guidelines for QM/MM DH-FEP calculations and default values for the required computational parameters. In the case of chorismate mutase, we apply the DH-FEP approach in combination with a single one-dimensional reaction coordinate and with a two-dimensional collective coordinate (two individual distances), with superior results for the latter choice.