Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.15.252247v1?rss=1 Authors: Motiwala, Z., Sandholu, A. S., Sengupta, D., Kulkarni, K. Abstract: Ras superfamily GTPases are molecular switches which regulate critical cellular processes. Extensive structural and computational studies on this G protein family have tried to establish a general framework for their switching mechanism. The current understanding of the mechanism is that two loops, Switch I and Switch II, undergo conformational changes upon GTP binding and hydrolysis, which results in alteration of their functional state. However, because of variation in the extent of conformational changes seen across the members of the Ras superfamily, there is no generic modus operandi defining their switching mechanism, in terms of loop conformation. Here, we have developed a novel method employing wavelet transformation to dissect the structures of these molecular switches to explore indices that defines the unified principle of working. Our analysis shows that the structural coupling between the Switch I and Switch II regions is manifested in terms of wavelet coherence phases. The resultant phase pertaining to these regions serve as a functional identity of the GTPases. The coupling defined in terms of wavelet coherence phases is conserved across the Ras superfamily. In oncogenic mutants of the GTPases the phase coupling gets disentangled, this perhaps provides an alternative explanation for their aberrant function. Although similar observations were made using MD simulations, there was no structural parameter to define the coupling, as delineated here. Furthermore, the technique reported here is computationally inexpensive and can provide significant functional insights on the GTPases by analyzing as few as two structures. Copy rights belong to original authors. Visit the link for more info