Monte Carlo studies of the mechanical properties of biopolymers

Biopolymers are one of the main components of living systems. Their sequence dictates their structure that ultimately determines their function. Many factors play key mechanical roles in the cell and one of the most abundant biopolymers that is involved in such tasks is the class of coiled-coil proteins. Various theoretical and experimental studies have been done to explore the mechanical properties of these proteins and there are now a number of single molecule measurements that measure their force response characteristics, making coiled-coils an excellent model system to test folding models connecting sequence to structure to function. In this thesis we have developed a coarse-grained atomistic model to study coiled-coil formation and explore both mechanical and thermal properties. Our model is able to reproduce known coiled-coil structures using only a simple hydrophobic-polar (HP) representation of their sequence and is able to explain the observed mechanical response measured in single molecule experiments. To address how common coiled-coil formation is with respect to all possible helix packs, we have evaluated the designability of the space of possible helical folds, defined as the number of sequences that can fold into a particular structure. We find that left-handed coils emerge as one of the most highly designable structures. From the designability calculation we can identify sequence patterns that design particular coiled-coil folds and mutations that lead to their instability. We also predict that designable coiled-coil structures are more mechanically stable than less designable helical packs.