  Statistical thermodynamics basis of energy and residue position fluctuations
is explained for native proteins. The protein and its surroundings are treated
as a canonical system with emphasis on the effects of energy exchange between
the two. Fluctuations of the energy are related to fluctuations of residue
positions, which in turn are related to the connectivity matrix of the protein,
thus establishing a connection between energy fluctuation pathways and protein
architecture. The model gives the locations of hotspots for ligand binding, and
identifies the pathways of energy conduction within the protein. Results are
discussed in terms of two sets of models, the BPTI and twelve proteins that
contain the PDZ domain. Possible use of the model for determining functionally
similar domains in a diverse set of proteins is pointed out.
