The adenine-thymine tautomer (A*-T*) has previously been
discounted
as a spontaneous mutagenesis mechanism due to the energetic instability
of the tautomeric configuration. We study the stability of A*-T* while
the nucleobases undergo DNA strand separation. Our calculations indicate
an increase in the stability of A*-T* as the DNA strands unzip and
the hydrogen bonds between the bases stretch. Molecular Dynamics simulations
reveal the time scales and dynamics of DNA strand separation and the
statistical ensemble of opening angles present in a biological environment.
Our results demonstrate that the unwinding of DNA, an inherently out-of-equilibrium
process facilitated by helicase, will change the energy landscape
of the adenine-thymine tautomerization reaction. We propose that DNA
strand separation allows the stable tautomerization of adenine-thymine,
providing a feasible pathway for genetic point mutations via proton
transfer between the A-T bases.