A detailed melting mechanism for DNA at the atomistic level is fundamental to the understanding of much of biochemistry and biotechnology. There are few molecular dynamics studies of this process to date. Previous work has proposed a two state mechanism for the unfolding but more recent studies have suggested multiple intermediates. Here molecular dynamics simulations of homo-oligomeric 4-mer and 8-mer duplexes were performed. Melting was induced by heating the systems to 373 K. The hydrogen bonding array was analysed using a newly developed definition which makes use of intermolecular potentials. The definition gives each hydrogen atom donating to only one acceptor atom at all times. The melting mechanism proposed goes via repeated fraying of terminal base pairs and shifting of the strands towards the 5' direction. This study identifies that there is a preference for unpaired bases formed to be at the 5' ends rather than the 3' ends. The fraying and shifting processes are thought to be induced by loss of planarity between base pairs. This mechanistic information is limited by the length and the homo-oligomeric nature of the strands considered. However, the proposed mechanism still gives an indication of the melting mechanism for more complex and biologically important DNA structures.
|Date of Award||1 Aug 2012|
- The University of Manchester
|Supervisor||Richard Henchman (Supervisor)|