4. Conclusions
Interactions between domains are responsible for the functionality of a
protein. Apart from functional advantages, domains in multi-domain
proteins provide additional stability to proteins and to the neighboring
domains. Studying types of domain interactions in multi-domain proteins,
focusing on their resident time becomes crucial to understand the
intra-protein interactions. In this current work, we recognized DDI
arising from two domains in a monomeric multi-domain protein as
permanent and transient using an algorithm used to classify PPIs. We
demonstrate that permanently interacting domains have larger interfaces
that facilitate larger number of interactions between the domains, which
in turn support stronger interactions. Their interfaces are populated by
a larger proportion of hydrophobic interactions, while transient domain
interfaces have comparatively lower hydrophobic interactions, which are
compensated by large number of side chain associated hydrogen bonding. A
comparatively increased number of residues in permanent domains have
highly correlated motions. Domains interacting permanently have a higher
chance of interacting with a structurally similar domain, and there are
a few topological biases for each interaction type. Furthermore, both
permanent and transient domains have equal number of conserved
interfacial residues, and the domains in the human genome do not
discriminate upon the functions or processes they are associated with.
We note that few of these observations are consistent with the way
permanent and transient PPIs differ from each other.
This work will be very useful to understand the molecular basis of
function and how the functional sites are disposed in 3D structure. This
analysis provides objective realization that two-domain monomeric
proteins which are permanently interacting are more likely to adorn
their interface by hydrophobic residues. This observation is certainly
of predictive value to obtain clues on biochemical function and to
recognize reasonable poses while performing domain-domain docking and
modeling.