ΔG). This optimization follows basic laws of thermodynamics described by the relationship ΔG = ΔH – TΔS, whereby the lowest free energy state is reached when enthalpy is most negative and entropy is most positive. Enthalpic energy is internal energy described by both covalent and noncovalent interactions between and within each level of organization. Covalent interactions that contribute to enthalpy are forces due to bond stretching, bond angle bending and torsion due to bond angle rotation. Electrostatic noncovalent interactions from strongest to weakest include salt bridges, hydrogen bonding and dipole interactions. Dipole interactions result from paired charges from any origin; therefore dipoles can result from H-bonded atoms or even the net opposite charges at helical termini. Van der Waals interactions also contribute to local and global enthalpy. These can be repulsive or attractive and only play a role upon close interaction between molecular electron density, or Van der Waals volumes. They are individually weak, yet they are many. Van der Waals interactions are cumulative therefore they play a significant role in protein folding. Entropy can be described as a measure of disorder, which is directly proportional to the local and global degrees of freedom for all structural units of the protein and solvent. A look at how energetics relate to helix folding illustrates the free energy balance. If a random coil that can sample a large number of conformational states folds into a relatively rigid α-helix, it loses a great deal of entropy. α-helices are very common in proteins and abide the free energy priority because the unfavorable loss in entropy is balanced by a favorable loss of enthalpy, which results from satisfying H-bonding potential of main chain carboxyl oxygen and NH groups.
             Understanding the organization of secondary, tertiary and quaternary structural elements is c...