A simple and very efficient protein design strategy is proposed by
developing some recently introduced theoretical tools which have been
successfully applied to exactly solvable protein models. The design
approach is implemented by using three amino acid classes and it is
based on the minimization of an appropriate energy function. For a given
native state the results of the design procedure are compared, through a
statistical analysis, with the properties of an ensemble of sequences
folding in the same conformation. If the success rate is computed on
those sites designed with high confidence, it can be as high as 80%. The
method is also able to identify key sites for the folding process:
results for 2ci2 and barnase are in very good agreement with
experimental results.
