  We recently introduced a physical model [Hoang et al., P. Natl. Acad. Sci.
USA (2004), Banavar et al., Phys. Rev. E (2004)] for proteins which
incorporates, in an approximate manner, several key features such as the
inherent anisotropy of a chain molecule, the geometrical and energetic
constraints placed by the hydrogen bonds and sterics, and the role played by
hydrophobicity. Within this framework, marginally compact conformations
resembling the native state folds of proteins emerge as broad competing minima
in the free energy landscape even for a homopolymer. Here we show how the
introduction of sequence heterogeneity using a simple scheme of just two types
of amino acids, hydrophobic (H) and polar (P), and sequence design allows a
selected putative native fold to become the free energy minimum at low
temperature. The folding transition exhibits thermodynamic cooperativity, if
one neglects the degeneracy between two different low energy conformations
sharing the same fold topology.
