INTERACTION WITH WATER INFLUENCES THE STRUCTURE OF BIOMOLECULES
Covalent and Noncovalent Bonds Stabilize Biologic Molecules
The covalent bond is the strongest force that holds molecules together (Table 2–1). Noncovalent forces, while of lesser magnitude, make significant contributions to the structure,
stability, and functional competence of macromolecules in living cells. These forces, which can be either attractive or repulsive, involve interactions both within the biomolecule and
between it and the water that forms the principal component of the surrounding environment.
Table 2–1 Bond Energies for A toms of Biologic Significance
Bond Type Energy (kcal/mol) Bond Type Energy (kcal/mol)
O—O 34 O=O 96
S—S 51 C—H 99
C—N 70 C=S 108
S—H 81 O—H 110
C—C 82 C=C 147
C—O 84 C=N 147
N—H 94 C=O 164
Biomolecules Fold to Position Polar & Charged Groups on Their Surfaces
Most biomolecules are amphipathic; that is, they possess regions rich in charged or polar functional groups as well as regions with hydrophobic character. Proteins tend to fold with the
R-groups of amino acids with hydrophobic side chains in the interior. Amino acids with charged or polar amino acid side chains (eg, arginine, glutamate, serine) generally are present on
the surface in contact with water. A similar pattern prevails in a phospholipid bilayer, where the charged "head groups" of phosphatidyl serine or phosphatidyl ethanolamine contact
water while their hydrophobic fatty acyl side chains cluster together, excluding water. This pattern maximizes the opportunities for the formation of energetically favorable charge–
dipole, dipole–dipole, and hydrogen bonding interactions between polar groups on the biomolecule and water. It also minimizes energetically unfavorable contacts between water and
hydrophobic groups.
Hydrophobic Interactions
Hydrophobic interaction refers to the tendency of nonpolar compounds to self-associate in an aqueous environment. This self-association is driven neither by mutual attraction nor by
what are sometimes incorrectly referred to as "hydrophobic bonds." Self-association minimizes the disruption of energetically favorable interactions between the surrounding water
molecules.
While the hydrogens of nonpolar groups such as the methylene groups of hydrocarbons do not form hydrogen bonds, they do affect the structure of the water that surrounds them.
Water molecules adjacent to a hydrophobic group are restricted in the number of orientations (degrees of freedom) that permit them to participate in the maximum number of
energetically favorable hydrogen bonds. Maximal formation of multiple hydrogen bonds, which maximizes enthalpy, can be maintained only by increasing the order of the adjacent
water molecules, with an accompanying decrease in entropy.
It follows from the second law of thermodynamics that the optimal free energy of a hydrocarbon–water mixture is a function of both maximal enthalpy (from hydrogen bonding) and
minimum entropy (maximum degrees of freedom). Thus, nonpolar molecules tend to form droplets that minimize exposed surface area and reduce the number of water molecules
whose motional freedom becomes restricted. Similarly, in the aqueous environment of the living cell the hydrophobic portions of biopolymers tend to be buried inside the structure of
the molecule, or within a lipid bilayer, minimizing contact with water.
Electrostatic Interactions
Interactions between charged groups help shape biomolecular structure. Electrostatic interactions between oppositely charged groups within or between biomolecules are termed salt
bridges. Salt bridges are comparable in strength to hydrogen bonds but act over larger distances. They therefore often facilitate the binding of charged molecules and ions to proteins
and nucleic acids.
van der Waals Forces
van der Waals forces arise from attractions between transient dipoles generated by the rapid movement of electrons of all neutral atoms. Significantly weaker than hydrogen bonds but
potentially extremely numerous, van der Waals forces decrease as the sixth power of the distance separating atoms (Figure 2–4). Thus, they act over very short distances, typically