A promising route to the synthesis of protein-mimetic materials that are capable of complex functions, such as molecular recognition and catalysis, is provided by sequence-defined peptoid polymers1,2—structural relatives of biologically occurring polypeptides. Peptoids, which are relatively non-toxic and resistant to degradation3, can fold into defined structures through a combination of sequence-dependent interactions3,4,5,6,7,8. However, the range of possible structures that are accessible to peptoids and other biological mimetics is unknown, and our ability to design protein-like architectures from these polymer classes is limited9. Here we use molecular-dynamics simulations, together with scattering and microscopy data, to determine the atomic-resolution structure of the recently discovered peptoid nanosheet, an ordered supramolecular assembly that extends macroscopically in only two dimensions. Our simulations show that nanosheets are structurally and dynamically heterogeneous, can be formed only from peptoids of certain lengths, and are potentially porous to water and ions. Moreover, their formation is enabled by the peptoids’ adoption of a secondary structure that is not seen in the natural world. This structure, a zigzag pattern that we call a Σ(‘sigma’)-strand, results from the ability of adjacent backbone monomers to adopt opposed rotational states, thereby allowing the backbone to remain linear and untwisted. Linear backbones tiled in a brick-like way form an extended two-dimensional nanostructure, the Σ-sheet. The binary rotational-state motif of the Σ-strand is not seen in regular protein structures, which are usually built from one type of rotational state. We also show that the concept of building regular structures from multiple rotational states can be generalized beyond the peptoid nanosheet system.
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Portions of this work were done as a User project at the Molecular Foundry at Lawrence Berkeley National Laboratory, supported by the Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under contract no. DE-AC02-05CH11231. R.V.M., T.K.H., C.P., E.J.R., A.B., R.N.Z. and S.W. were supported by the Defense Threat Reduction Agency under contract no. IACRO-B0845281. C.P. was also supported by the Natural Sciences and Engineering Research Council of Canada (NSERC PDF). R.N.Z. and S.W. were also supported by the Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under contract no. DE-AC02-05CH11231. We thank G. K. Olivier for providing the AFM data. This work used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the US Department of Energy under contract no. DE-AC02-05CH11231. Quantum-mechanical calculations were carried out on the High Performance Computing resources at New York University Abu Dhabi.
The authors declare no competing financial interests.
This file contains Supplementary Text, Supplementary Figures 1-27 and Supplementary Tables 1-2. (PDF 28974 kb)
This zipped file contains the latest structures in the Protein DataBank (PDB) format of the six peptoid nanosheet molecular dynamic simulations. (ZIP 5546 kb)
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Mannige, R., Haxton, T., Proulx, C. et al. Peptoid nanosheets exhibit a new secondary-structure motif. Nature 526, 415–420 (2015). https://doi.org/10.1038/nature15363
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