Computer simulations of peptide nucleic acid under external force

Abstract

The research question, “Can molecular dynamics be used to assess and screen the single-molecular binding properties of a candidate bioadhesive?" is answered in this thesis using molecular dynamics simulations. A ‘nearest-neighbour’ model was produced that related the candidate bioadhesive peptide nucleic acid’s (PNA’s) primary sequences with equilibrium binding enthalpies and could predict experimental binding enthalpies with an accuracy of 8.7%. In addition, the relationship between PNA rupture forces and loading rates at high loading rates was established for two distinct loading axes, and internal cohesive energies between two bound strands under external force were expressed as a function of displacements along unbinding coordinates. In addition, a novel coarse-grained model for ds-PNA that is natively integrable into other related coarse-grained models was produced and found capable of replicating both experimental structures and rupture forces as determined by all-atom models.This thesis presents the first time that the relationship between primary sequence and PNA binding energies have been derived. In addition, it presents the first time that the relationship between rupture force and loading rate has been established for PNA and the first time this relationship has been expressed in terms of inter-strand energies for PNA-containing nucleic acids. This thesis is of general interest for the development of a PNA bioadhesive by providing the single-molecular framework against which macroscopic observables can be interpreted and compared. In addition, the methods presented are broadly available and do not require specialist equipment, making them of interest to developing single-molecular interpretations of bioadhesive properties without significant financial or experimental investment