Semi-empirical QM/MM in amber

In a QM/MM calculation [31,32], the system is partitioned into two regions a QM region, typically consisting of a relatively small number of atoms relevant for the specific process being studied, and a MM region with all the remaining atoms. This scheme has been recently implemented in the Amber Molecular Dynamics package with support for various semi-empirical Hamiltonians [33,34], The total Hamiltonian (H) for such a system is written as... 

New versions of AMBER software support the option of allowing part of the system to be described quantum mechanically in an approach known as a hybrid (or coupled potential) QM/MM simulation. Both semi-empirical and the Density Functional Theory-based Tight Binding (DFTB) Hamiltonian can be used. The system may contain both two non-bonded parts and covalently bonded QM and MM sub-systems (Case et al. 2010). 

In practice, the localized orbital is extracted from a model small molecule computed with the same semi-empirical method and incorporated into the QM/MM scheme. This is the basis of the Local Self-Consistent Field [37] which consists in solving the Hartree-Fock equations relative to the quanffim subsystem in which the electronic interactions with the electrons of the localized bond as well as the classical point charges are included. The adaptation of the PM3 semi-empirical scheme [38] to the AMBER force-field [9] and the analytical expression of the energy derivatives and changes of coordinates led to the so-called classical-quantum force-field (CQFF) [39]. In this force-field, the first atom belonging to the classical part and linked to the quanffim part by means of the... 

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