3.2 Permanent domains have enhanced interfacial properties
To understand the interfacial features of DDIs within a single chain which could be responsible for their permanent and transient behaviour, we first investigated the total number of interactions through which two domains are held. We observed that most of the proteins having transient domains have a comparatively smaller number of interactions (Figure 2B). Also, around 91% of the transient domain containing proteins have interactions less than 75 in number. On the other hand, comparatively more permanent domain proteins have a larger number of interactions. The total number of interactions between permanent domains follow a near similar uniform distribution throughout different number of interaction ranges. We then computed interfacial areas to find the interface size of different domain-domain interfaces. From Figure 2C, we infer that proteins having transient domain interactions have comparatively smaller distribution of interface areas than proteins having permanent domain interactions. The interfacial areas of transient domain interactions are concentrated around the median of the distribution which suggests that these domains have smaller interfaces consistently. Instead, permanent domains of proteins have widespread interfacial areas, of which most of the domains have larger interfaces which is evident from comparatively large difference between upper quartiles in the boxplot. The domain pairs which have larger interfaces than 4000Å2 are listed in Supplementary Table S2, and most of the large transient domain interfaces are outliers (Figure 2C). This shows that permanent domains harbor larger elaborate interfaces than transient domains. The better the interaction energy of a complex, the stronger the binding and stability. For this case, we next checked the strength of domain interactions in these two kinds of interacting domains. From Figure 2D, it is observed that permanent domains indeed have better interaction energies than transient domains, as measured through PPCheck. The energies associated with permanent domains are more stabilizing than transient domains. It is also observed that the energies of transient domains are concentrated to a comparatively lower stabilizing energy, while the energies of permanent domains have a wide range of interaction strengths.
It is noteworthy that the number of permanent and transient domain containing proteins in our dataset are not equal, where we had comparatively a greater number of domain pairs in transient interactions than permanent ones. Therefore, we sampled random number of entries from transient domain pair dataset to match permanent domain pair dataset, and the observed trends are very similar to asymmetric dataset. Although, permanent domains have higher interfacial physical properties, it is also observed that both permanent and transient have similar average number of interactions per interfacial residue, 0.685 and 0.641 interactions per interfacial residue, respectively, which would mean that the residue interaction networks at the interface are not much different. The average number of interactions per interfacial residue is a proportional value and hence could be the reason for such similarity. The interface of such domain interaction types reveals many discriminatory facts that would help to distinguish permanent and transient domain interactions.