The Design of a Four-helix Bundle Protein

The design of proteins with predetermined structural properties is a necessary first step in the de novo design of novel enzymes and receptors. A major problem associated with the design of proteins is the high flexibility inherent in polypeptide chains. It has been estimated that a protein of 100 residues can adopt up to 10100 different conformations, a number that is as large as the number of atoms in the universe (Creighton 1984)! The mechanism by which a protein adopts a relatively well-defined set of conformations out of such a large number of possibilities is only beginning to be understood, and it is not possible to predict the three-dimensional structure of a protein from its amino acid sequence.