Density Functional Theory (DFT) is a powerful and
elegant electronic structure method for calculating ground state
properties of chemical systems. The main idea of DFT is to describe an
interacting electronic system via its electron density instead of its
many-body wave function. Although DFT is formally an exact theory,
practical applications of DFT are based on approximations for the
so-called exchange-correlation potential. The size and complexity of
the systems, that allow a DFT treatment, may range from a single atom
to a complex system containing around 200 atoms including transition
Thus, DFT provides, in combination with appropriate exchange-correlation potentials, accurate predictions for a variety of chemical properties at relatively low computational cost.
To accurately calculate vibrational spectra of cofactors imbedded in a protein matrix, one has to combine DFT with a molecular mechanics force field (MM) and molecular dynamics simulations (MD) to a so-called QM/MM hybrid approach. These methods include the protein matrix treated by empirical force fields (MM) whereas the cofactor is treated on the DFT level of theory. In this way, the effect of the protein matrix on the cofactors vibrational spectrum is explicitly taken into account.