Efficient Computation of Free Energy Surfaces of Diels⁻Alder Reactions in Explicit Solvent at Ab Initio QM/MM Level.

ABSTRACT: For 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 th

SUBMITTER: Li P 

PROVIDER: S-EPMC6222833 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature