Epsilon Archive for Student Projects

Abstract

The best-characterized epigenetic modification is DNA methylation, which was found to shape
significantly gene expression in mammalian cells, though bacteria and plants display less sequence
specificity. The cytosine methylation of DNA sequence here was studied by the molecular dynamic
(MD) method. We found that the optimized structures are not significantly altered between
unmethylated, methylated sequences. However, sampling of the molecule dynamical landscape via
long MD simulations showed that the altered sequences could adopt different conformations
(revealed in the twist and roll angles) from the unmodified DNA, which are dependent on the
§sequence environment. We propose that this conformational diversity may play a role on protein
recognition.
The G-rich sequences are studied with MD simulations to check the propensity of the sequence to
adopt to A-form or B-form of DNA. The results showed that the DNA sequence adopts most of the
time in A-form and also spend sometime in between A-form and B-form. The groove widths
showed the conformation in B-form. By analyzing the DNA in different contexts using
computational methods we were able to test limits that force field methods offer for these systems.
We propose that this conformational diversity may play a role in protein recognition.
Finally, we have studied the conformational changes of DNA sequence with uracil as a base.
Sometimes in the replication process uracil can be formed and the mismatch base pair in the DNA
sequence is removed by the enzyme UDG (Uracil-DNA sequence). In the present work MD
simulations were used to study the structure, dynamics and base pair kinetics of DNA sequence.
The opening and closing kinetics of the T-A base pair were studied. A fast base pair opening was
observed and also additionally base flipping was spotted. A very fast opening of the bases may be
responsible for the fast closing of the bases. In order to characterize the complete study of base pair
kinetics in relation to T-A versus U-A base pairs is currently under way.