Proteomics - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 404

are mainly composed of electrostatic energy, nonbonded energy, hydrogen bonded
energy, and torsional energy.
8.5.1.1 Electrostatic Energy
Electrostatic energy arises from ionic interactions that lead to attractive or repulsive
forces. This energy is inversely proportional to the dielectric constant of the medium.
Ionic interactions may take place between cationic groups, for example, in between
N-terminal amines like arginine and guanidine, and anionic groups like carboxylic
acid in aspartic and glutamic acid. As discussed earlier, these ionic interactions, and
thereby electrostatic energy, are inversely proportional to the dielectric constant of
the medium. Hence, there are poor ionic interactions in proteins in aqueous milieu,
leading to changed protein conformation in aqueous microenvironment as compared
to the same seen in a lipoidal atmosphere.
8.5.1.2 Hydrophobic Forces
Hydrophobic forces are the energy gained in removing hydrophobic groups from
water. This energy provides the catalyst for the hydrophobic clustering that may be
seen between the lipophilic side chains of many amino acids. Hydrophobic interac-
tions are key contributors to conformational energy in water.
8.5.1.3 Hydrogen Bonds
Hydrogen bonds are intermediate in terms of strength and length when compared
to van der waal's forces and covalent bonds. A hydrogen bond is mainly formed
between a donor atoms such as an amine, which acts as a ligand, or a lewis base and
acceptor atom like carboxylic acid. The larger the number of amino acids in a given
protein molecule, the greater is the probability of the formation of hydrogen bonds.
These interactions significantly contribute to conformational energy. The major ways
in which the chains fold to bring interacting groups together are primarily of four
different types: (1) -helix, (2) -structure, (3) reverse turns, and (4) random coils.
In the -helix, the peptide chains get coiled in the form of a helical structure with
hydrogen bonds between carbonyl groups of each residue and amide nitrogen of
the fourth residue. In the -sheet arrangement, there is a fully extended, unwound
flattened portion of the chain, whereas in random coils, there is no well-defined
structure.
8.5.1.4 Conformational Stability
Globular proteins tend to a single specific conformational structure. The overall con-
formational and topological features of a protein are mainly governed by (1) struc-
tural cross links composed of disulfide linkages and covalently bonded prosthetic
groups along with noncovalent cross-links like hydrogen bonds, hydrophobic inter-
actions, and miscellaneous forces and (2) continuous refolding to native conforma-
tions. Sometimes, the addition of organic solvent alters the conformational flexibility