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Open AccessArticle

Atomistic Analysis of ToxN and ToxI Complex Unbinding Mechanism

Shandong Key Laboratory of Biophysics and Institutes of Biophysics, Dezhou University, Dezhou 253023, China
National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University, Nanjing 210093, China
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(11), 3524;
Received: 17 September 2018 / Revised: 14 October 2018 / Accepted: 2 November 2018 / Published: 9 November 2018
ToxIN is a triangular structure formed by three protein toxins (ToxNs) and three specific noncoding RNA antitoxins (ToxIs). To respond to stimuli, ToxI is preferentially degraded, releasing the ToxN. Thus, the dynamic character is essential in the normal function interactions between ToxN and ToxI. Here, equilibrated molecular dynamics (MD) simulations were performed to study the stability of ToxN and ToxI. The results indicate that ToxI adjusts the conformation of 3′ and 5′ termini to bind to ToxN. Steered molecular dynamics (SMD) simulations combined with the recently developed thermodynamic integration in 3nD (TI3nD) method were carried out to investigate ToxN unbinding from the ToxIN complex. The potentials of mean force (PMFs) and atomistic pictures suggest the unbinding mechanism as follows: (1) dissociation of the 5′ terminus from ToxN, (2) missing the interactions involved in the 3′ terminus of ToxI without three nucleotides (G31, A32, and A33), (3) starting to unfold for ToxI, (4) leaving the binding package of ToxN for three nucleotides of ToxI, (5) unfolding of ToxI. This work provides information on the structure-function relationship at the atomistic level, which is helpful for designing new potent antibacterial drugs in the future. View Full-Text
Keywords: ToxIN; unbinding mechanism; molecular dynamics simulation; steered molecular dynamics simulation ToxIN; unbinding mechanism; molecular dynamics simulation; steered molecular dynamics simulation
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Hu, G.; Yu, X.; Bian, Y.; Cao, Z.; Xu, S.; Zhao, L.; Ji, B.; Wang, W.; Wang, J. Atomistic Analysis of ToxN and ToxI Complex Unbinding Mechanism. Int. J. Mol. Sci. 2018, 19, 3524.

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