QM/MM

QM/MM (Quantum mechanics/Molecular mechanics) approach is a molecular simulation method that combines the strength of both QM (accuracy) and MM (speed) calculations. The methodology for such techniques was introduced by Warshel and coworkers. In the recent years have been pioneered by several groups including: Arieh Warshel (University of Southern California), Weitao Yang (Duke University), Sharon Hammes-Schiffer (The Pennsylvania State University), Donald Truhlar and Jiali Gao (University of Minnesota) and Kenneth Merz (University of Florida).

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The most important advantage of QM/MM methods is the efficiency. The cost of doing classical molecular mechanics (MM) simulations in the most straight forward case scales O(n²), where N is the number of atoms in the system. This is mainly due to electrostatic interactions term (every particle interacts with everything else). However, use of cutoff radius, periodic pair-list updates and more recently the variations of the Particle mesh Ewald (PME) method has reduced this between O(N) to O(n²). In other words, if a system with twice many atoms is simulated then it would take between twice to four times as much computing power. On the other hand the simplest ab-initio calculations typically scale O(n³) or worse (Restricted Hartree-Fock calculations have been suggested to scale ~O(n^2.7)). To overcome the limitation, a small part of the system that is of major interest is treated quantum-mechanically (for instance, the active-site of an enzyme) and the remaining system is treated classically.

In more sophisticated implementations, QM/MM methods exist to treat both light nuclei susceptible to quantum effects (such as hydrogens) and electronic states. This allows generation of hydrogen wave-functions (similar to electronic wave-functions). This methodology has been useful in investigating phenomenon such as hydrogen tunneling. One example where QM/MM methods have provided new discoveries is the calculation of hydride transfer in the enzyme liver alcohol dehydrogenase. In this case, tunneling is important for the hydrogen, as it determines the reaction rate.^[1]

References

• Altoè P, Stenta M, Bottoni A, Garavelli M. (2007). "A tunable QM/MM approach to chemical reactivity, structure and physico-chemical properties prediction". Theor. Chem. Acc. 118: 219–240.[1]