In the first chapter we described the nature of the covalent chemical bonds in biological molecules and drug substances. In this chapter we will discuss the various non-covalent interactions that are important in biological molecules and in their interaction with drug molecules. Although non-covalent interactions are typically orders of magnitude weaker than covalent bonds, this does not imply that they are of less importance. As we will see, these “weak” interactions are what give proteins their particular three-dimensional shape and function, enable the copying of genetic information in DNA, and govern the interactions of drug molecules with their biological targets.
We can glean the importance of non-covalent interactions by looking at the structures of the amino acids that form proteins and the nucleotide bases present in DNA and RNA. Nature creates a huge diversity of structural and functional proteins using the same 20 amino acid building blocks (Table 2.1). Individual amino acids are distinguished by the chemical nature of their side chains. They can be roughly grouped into categories as being hydrophobic (leucine, valine, etc.), aromatic (phenylalanine, tryptophan), hydrophilic/uncharged (serine, glutamine), and hydrophilic/charged (lysine, arginine, aspartate, glutamate). This diversity is no accident—nature has selected for amino acids that are capable of forming a wide range of non-covalent interactions.
Structures of the Amino Acids Present in Protein Structure.
While proteins evolved primarily to serve structural and functional roles, the role of the DNA molecule is to store information. Here too nature has employed non-covalent interactions (hydrogen bonds and aryl-aryl ...