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Observation of a dewetting transition in the collapse of the melittin tetramer

Abstract

Marked hydration changes occur during the self-assembly of the melittin protein tetramer in water. Hydrophobicity induces a drying transition in the gap between simple sufficiently large (more than 1 nm2) strongly hydrophobic surfaces as they approach each other1,2,3,4,5,6, resulting in the subsequent collapse of the system, as well as a depletion of water next to single surfaces7,8,9,10. Here we investigate whether the hydrophobic induced collapse of multidomain proteins or the formation of protein oligimers exhibits a similar drying transition. We performed computer simulations to study the collapse of the tetramer of melittin in water, and observed a marked water drying transition inside a nanoscale channel of the tetramer (with a channel size of up to two or three water-molecule diameters). This transition, although occurring on a microscopic length scale, is analogous to a first-order phase transition from liquid to vapour. We find that this drying is very sensitive to single mutations of the three isoleucines to less hydrophobic residues and that such mutations in the right locations can switch the channel from being dry to being wet. Thus, quite subtle changes in hydrophobic surface topology can profoundly influence the drying transition. We show that, even in the presence of the polar protein backbone, sufficiently hydrophobic protein surfaces can induce a liquid–vapour transition providing an enormous driving force towards further collapse. This behaviour was unexpected because of the absence of drying in the collapse of the multidomain protein 2,3-dihydroxybiphenyl dioxygenase (BphC).

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Acknowledgements

We thank J. Castanos and his team for providing the running environment, and M. Eleftheriou, B. Walkup and A. Royyuru for help and support with the BlueGene/L machine. This work was supported in part by an NIH grant and an IBM SUR grant to B.J.B.

Author information

Correspondence to Ruhong Zhou or B. J. Berne.

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Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Supplementary information

Supplementary Notes

Supplementary Figures S1-S3 and a Supplementary Note are provided in the supporting material. Supplementary Figure S1: more trajectories for the number of water molecules inside the channel of melittin tetramer versus the MD simulation time. Supplementary Figure S2: more trajectories for the number of water molecules inside the channel of mutated melittin tetramer (single mutations). Supplementary Figure S3: the number of water molecules inside the melittin tetramer channel versus the dimer-dimer separation distance during the collapse of the tetramer. The Supplementary Note describes simulation of the melittin tetramer in its 'crystal environment'. (DOC 580 kb)

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Further reading

Figure 1: Dewetting in melittin.
Figure 2: Dewetting in mutated melittin.
Figure 3: Dewetting in a model system.

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