Recently developed polarizable force fields, such as AMOEBA, improve over commonly used fixed-charge classical approaches by including many-body electrostatic effects. However, using QM/MM approaches remains necessary in cases where electron transfer is involved, e.g. in catalysis. The development of QM/MM approaches employing polarizable force fields is still at an early stage. We describe TINKTEP: a QM/MM approach based on the ONETEP linear-scaling DFT code, and AMOEBA, as implemented in TINKER. The QM and MM subsystems are coupled electrostatically and through van der Waals interactions. A generalization of distributed multipole analysis (DMA) to localized orbitals optimized in situ is used to represent the QM density in terms of atom-centered multipoles. The use of this auxiliary representation enables treating QM/MM polarization interactions on the same footing as intra-MM polarization. The polarization response of the MM subsystem is determined self-consistently using TINKER. The total energy expression, which we minimize using gradient methods, accounts for permanent electrostatic, polarization and van der Waals interactions between the two subsystems. The electrostatic coupling of QM and MM is a highly non-linear problem, with a requirement for both descriptions to achieve self-consistency. We show how this necessitates careful consideration of the coupling, its effects on energy gradients, and suitable damping of electrostatic interactions. We validate the proposed approach on a number of model systems, demonstrating its advantages over fixed-charge QM/MM approaches. We envisage that this method will be useful for a wide range of chemical and biochemical grand challenge simulations.

TINKTEP: Polarizable QM/MM based on linear-scaling DFT and the AMOEBA force field

253rd National Meeting (2017)

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