We propose an application of molecular information theory
to analyze
the folding of single domain proteins. We analyze results from various
areas of protein science, such as sequence-based potentials, reduced
amino acid alphabets, backbone configurational entropy, secondary
structure content, residue burial layers, and mutational studies of
protein stability changes. We found that the average information contained
in the sequences of evolved proteins is very close to the average
information needed to specify a fold ∼2.2 ± 0.3 bits/(site·operation).
The effective alphabet size in evolved proteins equals the effective
number of conformations of a residue in the compact unfolded state
at around 5. We calculated an energy-to-information conversion efficiency
upon folding of around 50%, lower than the theoretical limit of 70%,
but much higher than human-built macroscopic machines. We propose
a simple mapping between molecular information theory and energy landscape
theory and explore the connections between sequence evolution, configurational
entropy, and the energetics of protein folding.