3.2 Global comparison in working dataset as compared to control
Next, the 895 cases from the bound versus unbound pairs of
protein chains are subject to global comparison by computing the network
dissimilarity score (NDS) and RMSD for structure deviation between
backbone conformations. The information obtained from the working
dataset is illustrated as a scatter plot as shown in Figure 1A. Similar
information obtained in the control where only multiple structures of
the same protein that are known to be single chain single domain is also
plotted in the background of the scatter. The statistics of the data
points corresponding to each of the datasets is marked with horizontal
and vertical lines to depict the mean of the data points. The structure
deviation in the control was about 0.34 Å with a standard deviation of
about 0.3 Å, whereas the mean deviation of the working dataset is about
1.14 Å with a standard deviation of about 0.94 Å. By performing a KS
test, it is also understood that the RMSD scores obtained in the working
dataset is significantly much higher than what was observed in the
control (p-value < 0.0001). Hence, the spread of the
topological variation of the backbone is much larger when proteins
undergo transient associations than the structural variability obtained
from multiple conformers of the same protein.
Likewise, the network dissimilarity observed in the control had a mean
of 0.112 ± 0.047 whereas that observed from the working dataset is 0.173
± 0.065. Also, KS-test results (p-value < 0.0001) show that
the dissimilarity in the networks is significantly higher in transiently
binding proteins as compared to the dissimilarity in PSNs of multiple
conformers of the same protein (control dataset). It is interesting to
analyse those cases where the variability in the network arises without
much change in the backbone conformation. The contribution to network
dissimilarity specifically arises from variability in local sidechain
conformations. The network comparison scores, and structure deviation of
these cases are greater and lower than mean of the dataset, respectively
and can be found clustered on the top left of the scatter shown in
Figure 1A. 194 cases from the working dataset show such a trend (with
RMSD < 1.14 Å and NDS > 0.173). A list of top
twelve cases with such network alterations are listed in Figure 1B, a
few highlighted cases are studied in detail.