Protein stability    

The  native  3-dimensional  conformation   of  protein  can be  maintained  by  a range of noncovalent  interactions  (electrostatic  forces, hydrogen  bonds, hydrophobic  forces)  and covalent  interactions  (disul?de  bonds)  in addition  to peptide bonds in between individual amino acids.

- Electrostatic forces: The Electro static interactions between the two ionic groups of opposite   charge,   for instance   the ammonium   group of Lys and  the  carboxyl group of Asp, generally referred to as an ion pair or salt bridge. In addition, noncovalent associations between electrically neutral molecules, referred collectively to as vander Waals forces, arise from electrostatic interactions in between permanent and induced dipoles, like the carbonyl group in peptide bonds.

- Hydrogen bonds: Hydrogen bonds are predominantly electrostatic interactions between weakly acidic donor group and an acceptor atom which bears a lone pair of electrons and hence has a partial negative charge, which attracts the hydrogen atom. In the biological  systems  the donor group is an oxygen  or nitrogen  atom which  has  a  covalently  attached  hydrogen  atom,  and  the  acceptor  is  oxygen  or  nitrogen  as shown in figure given below.  Hydrogen  bonds  are  generally  in  the  range 0.27–0.31   nm  and  are  very   directional,   that is,  the  donor,   hydrogen   and acceptor  atoms  are  collinear in nature.  Hydrogen  bonds  are much stronger  than the vander Waals  forces  but  much  weaker  than  the covalent  bonds.  Hydrogen bonds does not play an important  role in protein structure only,  but also in structure  of other biological macromolecules  like DNA double helix and lipid bilayers. Additionally, hydrogen bonds are critical to both properties of water and to its role as biochemical solvent.

-Hydrophobic   forces:  The  hydrophobic  effect  are  those forces  that cause  nonpolar  molecules  to reduce  their contact  with water. This can be clearly seen with amphipathic molecules like lipids and detergents which form micelles in aqueous solution. Proteins has a conformation  in which their nonpolar  side-chains  and are largely  out of contact with the aqueous solvent, and thus hydrophobic forces are an significant determinant  of protein structure, folding and stability. In proteins, effects of hydrophobic forces are termed as hydrophobic bonding, to show the speci?c nature of protein foldin  under  in?uence  of  hydrophobic effect.

- Disul?de  bonds: Disulfied covalent  bonds form between  Cys residues  which are close together  in ?nal conformation  of protein  as shown in figure given below and function  to  stabilize  its  3-dimensional structure.  Disul?de  bonds  are  formed in oxidizing environment  of the endoplasmic  reticulum,  and  thus  are  found   in  extracellular   and  secreted proteins primarily.