What is the Inverse protein folding problem ?

The inverse folding problem was originally defined by Drexler [1] and Pabo [2] as the problem of defining the sequences compatible with a given protein fold. It is fundamental to protein design and engineering, and, as such, as attracted considerable interest [3-8]. Since the function of a protein is directly related to its three dimensional structure, manipulation of the structure via the sequence changes can provide functional diversity. Protein molecules can be engineered to optimize their activities, as well as to alter their pharmacokinetic properties.

Background

The aim of protein sequence design is to generate sequences compatible with the target structure, but incompatible with competing folds. As such, there is one theoretical issue, and one computational problem to be solved. Here we provide links to general reviews that cover both subjects:

• Specificity versus Stability



• Searching the protein sequence space and structure space

Our Strategy for Protein Sequence Design

This link describes the method we have developed for solving this problem.