Design of amino acid sequences to fold into C_alpha-model proteins

In order to extend the results obtained with minimal lattice models to more realistic systems, we study a model where proteins are described as a chain of 20 kinds of structureless amino acids moving in a continuum space and interacting through a contact potential controlled by a 20x20 quenched random matrix. The goal of the present work is to design and characterize amino acid sequences folding to the SH3 conformation, a 60-residues recognition domain common to many regulatory proteins. We show that a number of sequences can fold, starting from a random conformation, to within a distance root mean square deviation (dRMSD) of 2.6A from the native state. Good folders are those sequences displaying in the native conformation an energy lower than a sequence--independent threshold energy.