The contrasting folding characteristics of three protein segments, each belonging to the same three-helix bundle family, have been the subject of experimental studies for more than a decade. These proteins (named R15, R16 and R17) are segment repeats from chicken brain alpha-spectrin. The reason behind the special interest in these three proteins is that, in spite of sharing a very similar tertiary structure and stability characteristics, their kinetics of folding and unfolding differ significantly. This is a feature which seems to challenge our understanding of the folding process, and which has puzzled the researchers who have come in contact with this problem.
In this thesis we describe the successive models and approaches taken to explore the free energy landscape of these proteins. Given the difficulties associated with experimental data acquisition at short time scales (faster than ms), it would be useful to develop an accurate and reliable computational model, so that the differences in the overall free energy landscape can be illustrated. For a protein system with so many exceptional characteristics, this proved to be an excellent opportunity to test and understand the implications and possibilities offered by each type of coarse grained model.