The stability of nucleic acid and protein polymers is primarily dependent on strong covalent bonds between the atoms of their linear backbones. In addition to covalent bonds, weak noncovalent bonds (Table 1) are important in stabilizing molecules and in allowing a variety of transient interactions between diverse molecules within cells. Whereas covalent bonds are comparatively stable, and require a high input of energy to break them, individual noncovalent bonds are typically >10 times weaker than individual covalent bonds. As a result, they are constantly being made and broken at physiological temperatures.
Table1. WEAK NONCOVALENT BONDS AND FORCES
The cellular environment is an aqueous one and the structure of water is particularly complex, with a rapidly fluctuating network of noncovalent bonding occurring between water molecules. The predominant force in this structure is the hydrogen bond, a weak electrostatic bond between fractionally positive hydrogen atoms and fractionally negative atoms (oxygen atoms, in the case of water molecules).
Charged molecules are highly soluble in water. Because of the phosphate groups in their component nucleotides, both DNA and RNA are negatively-charged polyanions. Depending on their amino acid composition, proteins may be electrically neutral, or they may carry a net positive charge (basic protein) or a net negative charge (acidic protein). All of these molecules can form multiple interactions with the water during their solubilization. Even electrically neutral proteins are readily soluble if they contain sufficient charged or neutral polar amino acids. In contrast, membrane-bound proteins with many hydrophobic amino acids are thermodynamically more stable in a hydrophobic environment.
Although individually weak, the combined action of numerous noncovalent bonds can make large contributions to the stability of the conformation (structure) of macro molecules and are important for specifying their shape. We describe in the next section how hydrogen bonds between pairs of bases are essential for maintaining the structure of DNA and RNA molecules; and in the final section of this chapter we illustrate the central role of hydrogen bonding in determining the shape of diverse structural motifs in proteins, including the classic α-helices, β-sheets, and so on.
Because noncovalent bonds are fragile and able to be broken and remade easily, they also allow transient interactions between different molecules. Hydrogen bonding is especially important in allowing transient interactions between different nucleic acids, facilitating the recognition by regulatory RNAs of target sequences in other RNAs or in DNA. We provide examples in different chapters, notably when we consider gene regulation.
