Abstract

The rotational switching of the bacteria flagella motor is controlled by binding of the signaling molecule CheY onto FliM which is a part of motor basal body. The rotational switching plays a central role in the bacterial chemotaxis. Recently, it was reported that high hydrostatic pressures of >120 MPa can induce the rotational switching even in the absence of CheY [1]. It was also suggested that hydration of the switch complex at high pressure induces structural changes similar to those caused by the binding of CheY. To gain further insights into the high pressure effect on the motor switching, we investigated differences in conformation of monomeric CheY and also CheY-FliM complex at different pressure conditions using molecular dynamics (MD) simulations. Then, pressure effects on the binding stability of the CheY-FliM complex was studied by dissociating the complex. The dissociation of the protein complex was observed using an efficient sampling method, PaCS-MD (Parallel Cascade Selection Molecular Dynamics) [2]. In PaCS-MD, the cycle of short MD simulations and selection of the structures close to the product structure for the next cycle are repeated, which enhances the conformational transitions without any additional external biases. From the obtained MD trajectories, the dissociation behavior was characterized using coordinates such as the center of mass (COM) distance and the number of native contacts between CheY and FliM. Moreover, potentials of mean force along the COM distance were calculated from probability distributions in steady state obtained by Markov state models. Those potentials of mean force provided binding free energies of the protein complex. Based on the results, we will also discuss mechanisms underlying influences of high hydrostatic pressures on the binding. Such insights would provide a further understanding towards an accurate regulation of protein-protein interactions.[1] Nishiyama, M. et al. 2013. J. Bacteriol. 195:1809-1814. doi: 10.1128/JB.02139-12.[2] Harada, R. and Kitao, A. 2013. J. Chem. Phys. 139:035103. doi: 10.1063/1.4813023.

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