Efficient Computation of Free Energy Surfaces of Diels–Alder Reactions in Explicit Solvent at Ab Initio QM/MM Level
AbstractFor Diels–Alder (DA) reactions in solution, an accurate and converged free energy (FE) surface at ab initio (ai) quantum mechanical/molecular mechanical (QM/MM) level is imperative for the understanding of reaction mechanism. However, this computation is still far too expensive. In a previous work, we proposed a new method termed MBAR+wTP, with which the computation of the ai FE profile can be accelerated by several orders of magnitude via a three-step procedure: (I) an umbrella sampling (US) using a semi-empirical (SE) QM/MM Hamiltonian is performed; (II) the FE profile is generated using the Multistate Bennett Acceptance Ratio (MBAR) analysis; and (III) a weighted Thermodynamic Perturbation (wTP) from the SE Hamiltonian to the ai Hamiltonian is performed to obtain the ai QM/MM FE profile using weight factors from the MBAR analysis. In this work, this method is extended to the calculations of two-dimensional FE surfaces of two Diels–Alder reactions of cyclopentadiene with either acrylonitrile or 1-4-naphthoquinone at ai QM/MM level. The accurate activation free energies at the ai QM/MM level, which are much closer to the experimental measurements than those calculated by other methods, indicate that this MBAR+wTP method can be applied in the studies of complex reactions in condensed phase with much-enhanced efficiency. View Full-Text
- Supplementary File 1:
PDF-Document (PDF, 331 KB)
Share & Cite This Article
Li, P.; Liu, F.; Jia, X.; Shao, Y.; Hu, W.; Zheng, J.; Mei, Y. Efficient Computation of Free Energy Surfaces of Diels–Alder Reactions in Explicit Solvent at Ab Initio QM/MM Level. Molecules 2018, 23, 2487.
Li P, Liu F, Jia X, Shao Y, Hu W, Zheng J, Mei Y. Efficient Computation of Free Energy Surfaces of Diels–Alder Reactions in Explicit Solvent at Ab Initio QM/MM Level. Molecules. 2018; 23(10):2487.Chicago/Turabian Style
Li, Pengfei; Liu, Fengjiao; Jia, Xiangyu; Shao, Yihan; Hu, Wenxin; Zheng, Jun; Mei, Ye. 2018. "Efficient Computation of Free Energy Surfaces of Diels–Alder Reactions in Explicit Solvent at Ab Initio QM/MM Level." Molecules 23, no. 10: 2487.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.