Simulation Aspects of the Mechanics of Biomolecular Filaments: Crackling in DNA unzipping and the Contraction of Bacteriophage Tails

Both DNA and the contractile tail sheaths of bacteriophages are examples of biofilaments, whose monomer subunits consist of nucleotides and proteins respectively. The bending and torsional deformations of tail sheaths and strand separation of ds-DNA are important phenomena essential for their biological functions. Despite the great prevalence and biomedical importance of contractile delivery systems, many fundamental details of their injection machinery and dynamics are still unknown. On a similar note, a detailed theoretical understanding of the monomer-level dynamics of DNA unzipping under constant force is also lacking in literature. In the subsequent chapters of this thesis, I will describe how computer simulations can be used to perform an in-depth study of both of the above phenomena. I would begin by describing a method which uses molecular dynamics simuations to calculate the bending and torsional stiffness constants of two biologically relevant contractile tail sheaths: bacteriophage T4 and R2-pyocin. Next, I would describe how the stiffness constants can be incorporated in a continuum dynamic model to simulate the dynamics of contractile nano-injection machineries. Finally, I would describe how MD simuations can be used to study the unzipping dynamics of a long DNA homopolymer, which would to a fascinating discovery where the 'avalanches' in the unzipping velocity time series show a power law variation in avalanche size and time similar to crackling noise in other unrelated physical systems. The studies of these phenomena are of great biological significance; studying contractile tail injection dynamics can open up new avenues in potential bio-nanotechnological applications like experimental phage therapy, and understanding of DNA unzipping at the monomer level is relevant to many essential genetic processes like replication, transcription, recombination, DNA repair, and -in biotechnology- to DNA sequencing