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particular, we found that hinges tend to coincide with active sites, but unlike the latter
they are not at all conserved in evolution. We evaluate the potential for hinge prediction
based on sequence.
Motions play an important role in catalysis and protein-ligand interactions. Hinge
bending motions comprise the largest class of known motions. Therefore it is important
to relate the hinge location to sequence features, namely residue type, flanking sequence,
physicochemical class, secondary structure, solvent exposure, evolutionary conservation,
and proximity to active sites. To do this, we first generated the Hinge Atlas, a set of
protein motions with the hinge locations manually annotated, and then studied the
coincidence of these features with the hinge location. We found that all of the features
have bearing on the hinge location. Most interestingly, we found that hinges tend to
occur at or near active sites and yet unlike the latter are not conserved. Less surprisingly,
we found that hinge residues tend to be small, not hydrophobic or aliphatic, and occur in
turns and random coils on the surface. A functional sequence based hinge predictor was
made which uses some of the data generated in this study. The Hinge Atlas is made
available to the community for further flexibility studies.
In Chapters 3 and 4 we will follow up our sequence based study of flexibility with
structure based studies. In Chapter 4 we will compare sequence based and structure
based methods.
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