The self-organisation of a denatured sequence to its native conformation, discussed in the previous section, has received significant recent attention [6, 5, 8]. Here we ask how the requisite sequence emerges from the functional need for the conformation via evolution (or any other method of sequence selection). The answer to this question is the objective of inverse protein folding.
The natural end of inverse protein folding is the prediction of stable, fast folding amino acid sequences which fold in situ to biologically useful target conformations. Proteins are densely packed macromolecules which function primarily by topographic surface recognition; accordingly, proteins should be designed to match the surface topography of their intended targets.
In Chapters 
- we attempt to do just this.
Along the way we answer questions such as:
1) Is the inverse problem well posed?
We want to design proteins to fold to arbitrary (compact) conformations.
Are protein targets limited in practise to those conformations to which
some sequence can fold?
2) Are biological proteins special?
In the previous section we saw that biological proteins fold to stable native
conformations over short times scales.
Is this typical of all proteins or does stable, fast folding occur for
exceptional sequences only?
3) How do we select a sequence to fold (quickly and stably) to a target?
Since the number of sequences grows exponentially, selecting for folding
performance by exhaustion quickly becomes prohibitive.
What properties of sequences correlate to folding ability?
Inverse protein folding inevitably tells us about the forward folding problem as well. To design sequences which successfully fold to their targets, we must understand what characterises good folding, on the one hand, and how such such sequences are selected, on the other. Folding ability may depend on our method of selection -- and the size of the space we select from -- in surprising ways.
The collapse of a linear chain of structural building blocks is an effective method of constructing complex macromolecules. Not surprisingly, ideas useful in protein design have applications outside their original context, such as the design of drugs and enzymes. Much of what we have to say applies to the engineering of useful heteropolymers in general.