Quantitative analyses were carried out on a large number of proteins that c
ontain the highly conserved basic helix-loop-helix domain. Measures derived
from information theory were used to examine the extent of conservation at
amino acid sites within the bHLH domain as well as the extent of mutual in
formation among sites within the domain. Using the Boltzmann entropy measur
e, we described the extent of amino acid conservation throughout the bHLH d
omain. We used position association (pa) statistics that reflect the joint
probability of occurrence of events to estimate the "mutual information con
tent" among distinct amino acid sites. Further, we used pa statistics to es
timate the extent of association in amino acid composition at each site in
the domain and between amino acid composition and variables reflecting clad
e and group membership, loop length, and the presence of a leucine zipper.
The pa values were also used to describe groups of amino acid sites called
"cliques" that were highly associated with each other. Finally, a predictiv
e motif was constructed that accurately identifies bHLH domain-containing p
roteins that belong to Groups A and B.