Protein , conformational states local unfolding

A folded native protein exists in a local minimum energy conformation. Typically 5 to 15kcal/mol free energy is sufficient to allow rapid interconversion (millisecond to second time scale) between folded and partially unfolded states. In general, proteins and peptides fold in a manner that minimizes the exposure of hydrophobic side chains of the peptide to water. 

The biological activity of proteins generally depends on a unique three-dimensional conformation, which in turn is inherently linked to its primary sequence. Protein folding, the conversion of the translated polypeptide chain into the native state of a protein, is the critical link between gene sequence and three-dimensional structure. Mechanistically, folding is believed to proceed through a predetermined and ordered pathway, either via kinetic intermediates or by direct transition from the unfolded to the native state [99]. In both cases, local and non-local interactions alike stabilize transient structures along the pathway and funnel the intermediates towards the native state. 

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