Introduction

The great variety of three-dimensional structures and functions of proteins arise in molecules that share underlying common features. Chemically, proteins are like strings of Christmas tree lights: each protein consists of a linear (i.e. unbranched) polymer mainchain with different amino acid sidechains attached at regular intervals (Fig. 1.6). The wire linking the string of lights corresponds to the repetitive mainchain or backbone, and the variable sequence of colours of the lights corresponds to the individuality of the sequence of sidechains.

The amino acid sequence of a protein is specified by the nucleotide sequence of a gene. The three-dimensional structures of protein molecules are determined, without further participation of nucleic acids, by the one-dimensional sequences of their amino acids. Proteins fold spontaneously to their native conformations.

How does the amino acid sequence encode the three-dimensional structure? Any possible folding of the mainchain places different residues into contact. The interactions of the sidechains and mainchain, with one another and with the solvent, and the restrictions placed on sidechain mobility, determine the relative stabilities of different conformations. This is a consequence of the second law of thermodynamics, which states that systems at constant temperature and pressure find an equilibrium state that is a compromise between comfort (low enthalpy, H) and freedom (high entropy, S), to give a minimum Gibbs free energy G = H - TS, in which T is the absolute temperature. (In human relationships, marriage is just such a compromise.)

Proteins have evolved so that...