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.