l - People

and the holo. In this case it is possible to compare the two structures and observe which
stretches of polypeptide are structurally conserved, i.e. are stable domains, and which
points are flexible. By doing so Van der Spoel et al.[110] determined the location of the
flexible hinge on the central helix of Calmodulin. The process can also be automated
with various available packages, including FlexProt[26, 27], Hingefind[28] and
DynDom[29]. A much more difficult problem is that of predicting hinges when only one
set of structural atomic coordinates is available. Several algorithms have been developed
for this purpose[19, 30-32]. The very hardest case occurs when the sequence is known
but atomic coordinates are not available.
The problem of finding flexible hinges between structural domains based on sequence is
in some ways similar to the problem of finding the boundaries of functional domains,
which can be flexible or inflexible. The latter are portions of a structure which recur in
various proteins performing a similar biochemical function; however these do not
necessarily coincide with the former [111]. Several algorithms exist to find the
boundaries of functional domains. In one significant contribution, Nagarajan and
Yona[33] analyzed multiple sequence alignments and were able to identify domains with
some accuracy. Marsden et al[34] focused on the case of proteins with no significant
sequence homology to well characterized proteins and found that predicted secondary
structure contained information about domain boundaries. Jones et al. combined
PUU[35], DETECTIVE[36], and DOMAK[37] to make a consensus-based domain
boundary predictor[38]. Heger et al. created the Automatic Domain Decomposition
Algorithm (ADDA) and associated online database. Murzin et al. created the SCOP
47