Protein folding raises some of biology's greatest theoretical challenges. It also lies at the root of many diseases. For example, the fundamental question of whether a protein's final tertiary conformation, sometimes called the native state, can be predicted from its primary amino acid sequence is also of vital importance in understanding the protein's potential capacity to form disease-inducing aggregates.
Protein folding is a hierarchical process, sometimes pictured as an inverted funnel, in three fundamental stages. All proteins begin with a primary amino acid sequence, which folds into intermediate secondary shapes comprising the well-known a helices and b sheets, and then into the final tertiary, or native form, in which they fulfill their function. Some proteins undergo a further phase, combining with other folded proteins to form quarternary structures.
The etiology of protein folding-related diseases can be investigated by forming predictive relationships between these structural layers, and understanding how subtle changes ...
