From Protein Structure to Function with Bioinformatics.pdf

242 M.B. Kubitzki et al.that contains more than 8,000 amino acids revealed a novel form of couplingbetween intra-ring and inter-ring cooperativity (de Groot et al. 1999). Each GroELring displays two main modes of collective motion: the main conformational transitionupon binding of the co-chaperonin GroES, and a secondary transition uponATP binding (Fig. 9.14 upper right panel). CONCOORD simulations of a singleGroEL ring did not show any coupling between these modes, whereas simulationsof the double ring system showed a strict correlation between the two modes,thereby providing an explanation for how nucleotide binding is coupled to GroESaffinity in the double ring, but not in a single ring.9.5 Summary and OutlookComputational methods gain growing recognition in structural biology and proteinresearch. Protein function is usually a dynamic process involving structural rearrangementsand conformational transitions between stable states. Since suchdynamic processes are difficult to study experimentally, in silico methods can significantlycontribute to the understanding of protein function at atomic resolution.Fig. 9.14 Asymmetric GroEL-GroES complex (left), together with CONCOORD simulationresults (right). The GroEL-GroES complex consists of the co-chaperonin GroES (blue), the transringof GroEL, bound to GroES (red), and the cis-ring (green). A principal component analysisrevealed two main structural transitions per GroEL ring, upon nucleotide binding (vertical axis inthe right panels) and GroES binding (horizontal axis), respectively. In simulations of the doublering, but not in a single ring, these modes were found to be coupled, suggesting a couplingbetween intra-ring and inter-ring cooperativity