Structural evolution of proteinlike heteropolymers.

The biological function of a protein often depends on the formation of an ordered structure in order to support a smaller, chemically active configuration of amino acids against thermal fluctuations. Here we explore the development of proteins evolving to satisfy this requirement using an off-lattice polymer model in which monomers interact as low resolution amino acids. To evolve the model, we construct a Markov process in which sequences are subjected to random replacements, insertions, and deletions and are selected to recover a predefined minimum number of solid-ordered monomers using the Lindemann melting criterion. We show that polymers generated by this process consistently fold into soluble, ordered globules of similar length and complexity to small protein motifs. To compare the evolution of the globules with proteins, we analyze the statistics of amino acid replacements, the dependence of site mutation rates on solvent exposure, and the dependence of structural distance on sequence distance for homologous alignments. Despite the simplicity of the model, the results display a surprisingly close correspondence with protein data.