A variety of functions of proteins are achieved by cooperative motions
of their constituent atoms. This cooperativity is further achieved by
crosstalk among domains of the proteins either by physical contacts or
by correlated motions of its atoms. To explore any discrimination of
dynamic behavior of residues between permanent and transient domains, we
studied residue cross-correlation of motions, which are represented by
Cα atoms using Anisotropic Network Model (ANM) of
Normal Mode Analysis (NMA). Cross-correlation values range from -1 to 1,
and we considered those residue pairs to be highly correlated if their
value is greater than 0.7 to keep a balance between the number of
correlated residues and their high correlation. Figure 4 shows the
differences in inter-residue correlated motions between domains
interacting permanently and transiently. Residues from permanent domain
pairs showed a wider range of highly correlated motions than residues
from transient domains. When the data were plotted in a histogram to
better understand the difference, we found maximum number of transient
domain pairs to have extremely low percentages of highly correlated
residues, while consistently, a greater number of permanent domain pairs
showed a higher percentage of highly correlated residues (Supplementary
Figure S2). The same analysis was tested with different cutoffs to
define high residue correlations ranging from 0.5 to 0.9, and the
patterns obtained were similar. This observation implies that the
domains which interact transiently carry out short range correlated
motions, whereas in case of permanent domains, extensive interactions
are going on across domains and can engage in long range correlated
motion. The range here conveys the strength of interaction or force of
movement using a large number of residues (long) or a small number of
residues (short).
Such behavior of permanent domains could be thought of due to their
lifetime of interactions. These residues are needed to be synchronous to
maintain the integrity of the domain interface, and this correlated
motion would help the domains to maintain resonance for the stability of
the monomeric protein. On the other hand, transient domains would need
to associate and dissociate frequently. Comparatively lower percentage
of highly correlated residues between domains would be enough to
maintain the interface and hence the transient nature. This clearly
conveys how dynamics is associated with the long-term interactions
within protein interiors.