Foundations of biomolecular modeling

Abstract

The 2013 Nobel Prize in Chemistry has been awarded to Martin Karplus, Michael Levitt, and Arieh Warshel for "development of multiscale models for complex chemical systems." The honored work from the 1970s has provided a foundation for the widespread activities today in modeling organic and biomolecular systems.

Figure 1. Combining Quantum and Molecular Mechanics to Explore Excited States

Upon exposure of a conjugated molecule like stilbene (illustrated) to sufficiently energetic photons, an electron can be excited from the highest occupied molecular orbital (bottom) to the lowest unoccupied one (top). To compute the energy change for such transitions from the ground electronic state to excited states requires a quantum mechanical (QM) treatment for at least the π orbitals. To also compute the relative energies and excitation energies for alternative conformers, treatment of the energy of the rest of the molecule is also required, e.g., by molecular mechanics (MM). Such a hybrid approach was used by the honorees (Warshel and Karplus, 1972).

Figure 2. QM/MM for Enzymatic Reactions

Mixed quantum and molecular mechanics calculations are used to model enzymatic reactions. The substrate and key surrounding residues are treated with QM, while the remainder of the system including water molecules is represented with faster molecular mechanics (Warshel and Levitt, 1976).