| This thesis describes the modeling of the triple helix of collagen for characterizing the mutations associated with collagenous disease. Chapter one introduces the material and summarizes the findings of this work. In chapter two, I describe the quantitative validation of mutant and wildtype collagen-like peptide models. Chapter three describes the development of parameters for simulating substituted proline residues and the effects of those parameters on the conformation of the triple helix. Those parameters are then used to simulate the triple helix and their effect on conformation and solvent structure. Using my model, chapter four describes the simulation of many serine, valine, cysteine and alanine disease associated mutations and described the structural changes that occur between the mutant and normal peptides. Finally in chapter five, I give perspective on these results and speculate on the future direction of this project. The appendix describes an evolutionary approach to characterizing disease associated genetic variation. |
