Hybrid QM/MM Potentials of Mean Force with Interpolated Corrections

Abstract

Because of its computational cost, QM/MM simulations are usually carried out using low-quality Hamiltonians, such as semiempirical, which are not always able to provide an accurate potential energy surface. We here propose a simple but efficient way to obtain corrected quantum mechanics/molecular mechanics (QM/MM) potentials of mean force (PMF) for chemical processes in condensed media. By means of dual-level calculations on the QM subsystem, we evaluate a correction energy term by employing either the polarized or the unpolarized wave functions. This energy term is evaluated as a function of the distinguished reaction coordinate biased in the calculation of the PMF. Using a mapping coordinate and splines under tension, its derivatives can be readily included to perform molecular dynamics simulations. The structures selected to evaluate the energy correction are chosen from a reaction path obtained in the condensed media, ensuring then that they are representative of the ensemble of structures sampled during the simulation. We have tested the proposed scheme with two prototypical examples: the Menshutkin reaction in aqueous solution and the chorismate rearrangement to prephenate catalyzed by Bacillus subtilis chorismate mutase. In both cases the use of interpolated corrections clearly improves the quality of the results.

Theoretical Study of the Phosphoryl Transfer Reaction from ATP to Dha Catalyzed by DhaK from Escherichia coli

“…In order to reduce the errors associated with the quantum low-level PM3 employed in our simulations, following the studies of Truhlar et al, [63][64][65] an interpolated correction term was applied to any value of the reaction coordinate ξ, selected to generate the FES. Then, a continuous new energy function was generated that corrects the PMFs, as previously performed in our laboratory: [66][67][68] …”

Unraveling the Reaction Mechanism of Enzymatic C5-Cytosine Methylation of DNA. A Combined Molecular Dynamics and QM/MM Study of Wild Type and Gln119 Variant

“…Therefore, we were able to take into account multiple variables that conform the best global reaction coordinate at each step, were calculated using statistical bootstrap technique 60 with 1000 samples generated from the original data from Umbrella Sampling. PMFs were obtained using interpolated corrections 61,62 along the s coordinate:…”

Multidimensional Tunneling, Recrossing, and the Transmission Coefficient for Enzymatic Reactions

“…The QM/MM interaction accounts for the polarization of the wave function of the reaction center by the environment. 433 The choice for the QM method is typically a semiempirical electronic structure method, such as Austin model 1 (AM1) 434 or parametrized model 3 (PM3), 435 404,412,440,441 can be used to improve the quality of the potential energy surface in order to achieve quantitatively accurate results for dynamics. In our applications so far, the generalized hybrid orbital (GHO) 31,113,169,[442][443][444][445][446][447] method is adopted to provide an electrostatically stable and smooth connection between the QM and MM regions; however, other QM/MM methodologies 448 can also be used.…”