  Proteins are a matter of dual nature. As a physical object, a protein
molecule is a folded chain of amino acids with multifarious biochemistry. But
it is also an instantiation along an evolutionary trajectory determined by the
function performed by the protein within a hierarchy of interwoven interaction
networks of the cell, the organism and the population. A physical theory of
proteins therefore needs to unify both aspects, the biophysical and the
evolutionary. Specifically, it should provide a model of how the DNA gene is
mapped into the functional phenotype of the protein.
  We review several physical approaches to the protein problem, focusing on a
mechanical framework which treats proteins as evolvable condensed matter:
Mutations introduce localized perturbations in the gene, which are translated
to localized perturbations in the protein matter. A natural tool to examine how
mutations shape the phenotype are Green's functions. They map the evolutionary
linkage among mutations in the gene (termed epistasis) to cooperative physical
interactions among the amino acids in the protein. We discuss how the
mechanistic view can be applied to examine basic questions of protein evolution
and design.
