mohammad tabish ahmed - eTheses Repository - University of ...

Chapter 1
1.1 Protein Folding
The genome sequence of an organism is the basic information required by an organism to
live. This code is read, translated and acted upon by the cell to maintain itself. Proteins
represent the final stages of information transfer from an organism‟s genome sequence. It
takes just 20 amino acids to form all the known and unknown proteins. A single error in the
mechanism of protein folding in an organism can have an adverse affect on its survival
capabilities. This, along with the importance of proteins in the medical and biotechnological
fields makes the study of protein folding vital, as the final structure of the protein determines
its activity. Even though the mechanism of protein folding is a very active area of research,
exactly how the linear amino acid sequences are folded into fully functional proteins is yet to
be conclusively answered.
1.1.1 A brief historical perspective of protein folding
Proteins were first recognised in the 18 th century, but it wasn‟t till the 19 th century that the
term protein came into use. Even then it took almost another century before scientists started
to study the processes involved in protein folding. In 1959, W. Kauzmann discovered that
protein folding is mediated by hydrophobic interactions (Kauzmann, 1959). This then led to
the idea that proteins fold in a trial and error manner. However, in 1968 Levinthal suggested
that if proteins were folding in a „trial and error‟ method, then it would take longer than the
age of the universe for a protein to reach its native state (Levinthal, 1968) . A thermodynamic
hypothesis was then put forward which suggested that a protein would reach its native state
when its Gibbs free energy was at its lowest. Anfinsen demonstrated that the free energy of a
protein was determined by its inter-atomic interactions, which were in turn determined by the
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