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.