ABSTRACT
The folding problem, namely how a freshly synthesized polypeptide chain reaches its secondary, tertiary and sometimes quaternary structure belonging to the native state, has been studied widely in the last decades. Folding of the polypeptide chain into the native conformation is not always successful. There are intermediate conformations on the folding pathway where intermolecular interactions can become favorable, which leads to aggregation and misfolding of the protein. These aggregates can be deposited either in the cell or in the extracellular space. Such insoluble tissue deposits of water soluble proteins can be observed in several serious diseases. The folding experiments all start with a sample, containing the aqueous solution of the folded protein. That is why the experiment must start with an unfolding step. High pressure can unfold proteins which consequently can be used for (re)folding studies. During the refolding, metastable states can be populated, which have increased aggregation propensity.
