De novo and rational protein design are progressing towards the chemic
al synthesis of proteins with pre-selected structure and function. The
data illustrate diverse experimental and computational approaches whi
ch test our comprehension of protein structure, hydrophobic core packi
ng and global stability, especially of coiled-coil proteins. The incor
poration of biological cofactors, including hemes, as well as active s
ites, such as that of iron superoxide dismutase, into designed protein
s provides an exciting next step towards the synthesis of proteins wit
h enzymatic function.