Figure 1. Absorption of UV light leads to the formation of a Thymine dimer, as shown in these snapshots from an ab initio MD simulation.To survive exposure to UV radiation, organisms have evolved complex mechanisms to repair damaged DNA. The initial step is usually the detection of a damage spot, a thymine dimer for instance. Subsequently, the dimer is either repaired, or completely removed.
Photolyase is an enzyme that detects the dimer site by binding to it
and then catalyses the splitting of the dimer into the original
pyrimidine bases (Figure 2). Photolyase contains a reduced flavin
co-enzyme co-factor that upon absorption of UV light donates an
electron to the bound Thyime dimer. The excess electron destabilizes
the dimer, and facilitates the slitting of the cyclobutane ring. After
the original thymine bases are restored, the electron flows back onto
the flavin and Photolyase is ready to repair the next lesion.
The tutorial is aimed at learning the elementary QM/MM skills one
needs for studying biological systems. The tutorial consists of eight
sections:
We will use the following software packages in this tutorial
Figure 2. Photolyase-DNA complex. Photolyase
uses UV light to catalyze the restoration of the original thymine
bases (red).
Thymine dimers can also be restored without the help of Photolyase. In
this so-called self-repair process, the dimer splits upon spontaneous
uptake of an electron. Depending on the base sequence, such electrons
are readily available. In this tutorial we will examine the self
repair process by means of ab initio molecular dynamics
simulations.