The protein folding problem is of direct medical relevance due to the pathogenic effects caused by improperly folded proteins in various cancers and in diseases such as Alzheimer's and Creutzveldt-Jakob disease. The conformational or folding free energy landscape of a small beta-clamshell protein will be characterized by examining its most interesting and relevant features: the native, denatured, transition state, and intermediate ensembles. Due to the conformational heterogeneity of these ensembles, a synergistic approach of both theory and experiment is required to fully characterize the energy landscape. A quantitative picture of the energy landscape will be generated and the kinetics of the folding process on the landscape will be computed and compared to experimental kinetic data. A full kinetic and thermodynamic picture of the folding of a small beta-clamshell protein will thus be generated.
