Reactive force field molecular simulation methods

The most basic approach to carry out MD simulations for larger systems is to use classical force fields. A variety of different force fields for molecular mechanics (MM) simulations has been developed,which are mainly intended to describe the non-reactive dynamics of large systems. In particular in the field of biochemistry force fields play an essential role to study the complex properties of large biomolecules. However, classical force fields require the specification of the connectivity of the atoms. Therefore, they are not able to describe chemical reactions, i.e., the making and breaking of bonds. To describe reactions, they can be combined with quantum mechanical (QM) methods in so-called QM/MM simulations. In recent years also reactive force fields , e.g. ReaxFF, have been introduced, which overcome this limitation. However, these reactive force fields are typically highly adapted to specific systems by analytic terms customized to describe e.g. certain bonding situations, and only a few applications have been reported so far. 

Our theoretical investigation regarding the understanding of the conversion of iminium into enamine in the framework of a proline-catalyzed aldol reaction emphasizes that the reactive force field (FF), ReaxFF, used in combination with molecular dynamics (MD) simulations is a relevant method to investigate the mechanism of proton transfers in iminium-enamine conversions. This approach should be extended to model other steps of proline-catalyzed... 

At least two recent trends within computational chemistry, depending on the increasing computational strength and on algorithm development, can be identified first, the exploration of the domain between electronic structure calculations and molecular level simulations using methods such as QM/MM, Car-Parrinello, reactive force fields, etc. second, multiscale modelling, where results from complex level calculations are used as input in more macroscopic approaches in a coupled model. ... 

Despite advent of theoretical methods and techniques and faster computers, no single theoretical method seems to be capable of reliable computational studies of reactivities of biocatalysts. Ab initio quantum mechanical (QM) methods may be accurate but are still too expensive to apply to large systems like biocatalysts. Semi-empirical quantum methods are not as accurate but are faster, but may not be fast enough for long time simulation of large molecular systems. Molecular mechanics (MM) force field methods are not usually capable of dealing with bond-breaking and formation... 

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