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.