Quantum Mechanical Insights into Biological Processes at the Electronic Level - Computational Modeling of Biological Systems - page 146

the analysis of enzymatic mechanisms, and, in the case of artificial enzymes, for
the detection of potential structural problems with designs and providing recipes for
their improvement and rescue.
The number of applications and variations on the theme of QM/MM is enormous,
and the field still gains momentum, suggesting its even greater popularity in the
near future. The basic principle of QM/MM is always the same: partitioning the
system into the more chemically significant part and the rest, treat the two parts with
theory of different accuracy and cost, and take good care of how the two subsystems
communicate.

4 Excited States and Electron Detachment

4.1 Theoretical Foundation

Excited electronic states frequently occur in biology. They may form when molecules
absorb ultra violet light coming from the Sun, for example. Electronic excitations
may happen by promoting an electron from the highest unoccupied MO (HOMO),
or from deeper occupied MOs to one of the bound unoccupied MOs. Hence,
there is a whole spectrum of excited electronic states accessible to the molecule.
Higher energy radiation may induce the photoelectric effect in biomolecules, i.e.,
electron detachment from one of the valence MOs to the continuum, yielding a
photoelectron spectrum. Needless to say that electronic excitation and detachment
energies characteristic of molecules can be used as spectroscopic probes for their
structure and electronic properties. Furthermore, molecules excited to one of the
excited PESs will evolve according to gradients for the nuclear motion characteristic
of this PES. This evolution may lead to the formation of various photoproducts,
sometimes irreversibly. This is relevant to photodamage of molecules such as, for
example, DNA in our cells. Alternatively, the system may fluoresce, if it gets trapped
on one of the “dark” exited states. Also, electronic excitations are the key to the
catalytic activity of photoactivated enzymes.
A computational description of excited states requires special methods. The least
computationally expensive applicable method is a variant of DFT, called time-
dependent DFT, or TD-DFT. In TD-DFT, there is a time-dependent potential to
which the system is exposed, and it is postulated that this potential uniquely maps
onto the time-dependent electron density of the system [ 25 ]. TD-DFT is a linear
response type of method, which is based on the assumption that the reference ground
state is perturbed relatively little upon the presence of the time-dependent field, and
so the ground state solutions can be used throughout. The poles in the response
function correspond to excitation energies of the system.
The method works well for well-separated ground and excited PESs. However,
being intrinsically single-configurational, TD-DFT cannot handle states that are