Robustness and efficiency in inverse protein folding

Successful protein design is characterized by two criteria: thermodynamic robustness, the probability of occupation of the target conformation, and kinetic efficiency, the ability of the protein to quickly fold to its target state. We observe a conflict between robustness and efficiency upon variation of both the pair potential matrix and the designed sequence. We argue that marginal reduction in thermodynamic robustness can provide significant increase in kinetic efficiency, thereby allowing improved protein design.