Protein folding is the physical process by which a protein chain acquires its native 3-dimensional structure, a conformation that is usually biologically functional, in an expeditious and reproducible manner. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil. Each protein exists as an unfolded polypeptide or random coil when translated from a sequence of mRNA to a linear chain of amino acids. This polypeptide lacks any stable (long-lasting) three-dimensional structure (the left hand side of the first figure). As the polypeptide chain is being synthesized by the ribosome, the linear chain begins to fold into its three dimensional structure. Folding begins to occur even during translation of the polypeptide chain. Amino acids interact with each other to produce a well-defined three-dimensional structure, the folded protein (the right hand side of the figure), known as the native state. The resulting three-dimensional structure is determined by the amino acid sequence or primary structure (Anfinsen's dogma).[2] The energy landscape describes the folding pathways in which the unfolded protein is able to assume its native state. Experiments beginning in the 1980s indicate the codon for an amino acid can also influence protein structure.

The correct three-dimensional structure is essential to function, although some parts of functional proteins may remain unfolded, so that protein dynamics is important. Failure to fold into native structure generally produces inactive proteins, but in some instances misfolded proteins have modified or toxic functionality. Several neurodegenerative and other diseases are believed to result from the accumulation of amyloid fibrils formed by misfolded proteins. Many allergies are caused by incorrect folding of some proteins, because the immune system does not produce antibodies for certain protein structures.

Primary Structure :
The primary structure of a protein, its linear amino-acid sequence, determines its native conformation.[7] The specific amino acid residues and their position in the polypeptide chain are the determining factors for which portions of the protein fold closely together and form its three dimensional conformation. The amino acid composition is not as important as the sequence.[8] The essential fact of folding, however, remains that the amino acid sequence of each protein contains the information that specifies both the native structure and the pathway to attain that state. This is not to say that nearly identical amino acid sequences always fold similarly.[9] Conformations differ based on environmental factors as well; similar proteins fold differently based on where they are found.

Secondary Structure:
Formation of a secondary structure is the first step in the folding process that a protein takes to assume its native structure. Characteristic of secondary structure are the structures known as alpha helices and beta sheets that fold rapidly because they are stabilized by intramolecular hydrogen bonds, as was first characterized by Linus Pauling. Formation of intramolecular hydrogen bonds provides another important contribution to protein stability. Alpha helices are formed by hydrogen bonding of the backbone to form a spiral shape (refer to figure on the right).The beta pleated sheet is a structure that forms with the backbone bending over itself to form the hydrogen bonds (as displayed in the figure to the left). The hydrogen bonds are between the amide hydrogen and carbonyl carbon of the peptide bonds.

Tertiary Structure

The alpha helices and beta pleated sheets can be amphipathic in nature, or contain a hydrophilic portion and a hydrophobic portion. This property of secondary structures aids in the tertiary structure of a protein in which the folding occurs so that the hydrophilic sides are facing the aqueous environment surrounding the protein and the hydrophobic sides are facing the hydrophobic core of the protein.[11] Secondary structure hierarchically gives way to tertiary structure formation. Once the protein's tertiary structure is formed and stabilized by the hydrophobic interactions, there may also be covalent bonding in the form of disulfide bridges formed between two cysteine residues. Tertiary structure of a protein involves a single polypeptide chain; however, additional interactions of folded polypeptide chains give rise to quaternary structure formation.

Chaperone Concept : The Chaperones assist in the correct folding pattern of a protein.If Chaperone fails to do so then Protein ultimately becomes Prion protein which gives rise to several diseases lile Kuru , Scrapie disease and Alziemers.