Beyond QM/MM: Fragment Quantum Mechanical Methods

The 2013 Nobel Prize in Chemistry was awarded to three chemists for their contributions in the early 1970s to combined quantum mechanical and molecular mechanical (QM/MM) methods, a class of multiscale models, to study chemical and biological reactions. In the past 20 years, this approach has matured to become a method of choice for large systems. However, there are also several well-known limitations that cannot be resolved within the framework of either MM or combined QM/MM. In principle, quantum mechanics can provide both reactive and nonreactive potential energy surfaces. Currently, there is a burst of exciting advancement that involves the representation of the entire macromolecular system directly by quantum chemical models. These methods, in one way or another, rely on the partition of a large system into molecular fragments such that the computational cost is reduced.

To highlight recent developments and applications of fragment quantum mechanical methods, a special issue, which was co-edited by professors Jiali Gao from the Department of Chemistry at the University of Minnesota, John Z. H. Zhang from the East China Normal University and NYU-Shanghaim, and Kendall N. Houk from UCLA was just published in Accounts of Chemical Research. These techniques can be used either as an electronic structure theory for macromolecules or as a quantum mechanical force field (QMFF) in molecular dynamics simulations. Both directions represent paradigm-shifting advances in the way that we represent and model complex systems. Read the Special Issue Editorial.