The 7th Peptoid Summit highlighted progress in design technology for one of the most promising toolkits in modular molecular systems engineering.
I’ve outlined the submonomer method for peptoid synthesis as a powerful and convenient way to assemble diverse molecular components, and the recent development of crystalline peptoid nanosheets as a platform for extended atomically-precise structures. The Summit reported further progress in structure prediction and in design for predictability: for example, selection of sidechains to control cis and trans amide conformations (Aaron Crapster University of Wisconsin), selection of rigid monomers and backbone interactions to restrict rotation (Bishwajit Paul, New York University), molecular mechanics and RosettaDesign-related methods for conformational prediction and engineering (Richard Bonneau,* New York University), molecular dynamics simulations (Vincent Voelz, Simprota Corporation), and systematic peptoid force-field development (Dina Mirijanian, LBNL).
Ron Zuckermann of LBNL (peptoid pioneer, ongoing leader, great guy) reported results at the biomolecular/inorganic materials interface — peptoids that direct the rate and form of crystal growth in calcium carbonate — and progress in understanding the mechanisms that enable the formation of large peptoid nanosheets.
The sheets form when a solution of suitably-engineered peptoids is shaken (not stirred). The molecules are a peculiar kind of surfactant, and they assemble into a monolayer at the air-water interface. Bubble formation and destruction creates and destroys interfacial area: this drives the formation of monomolecular surface films, then forces them to enter the bulk fluid as bilayers. Next steps will explore more controlled methods using a Langmuir-Blodgett trough.
Exploiting fluid interfaces to direct self-assembly
To generalize, this points to the utility of fluid interfaces for preorganizing molecular components (not necessarily sheets) on the way to forming soluble structures. An amphiphilic molecule or aggregate at an interface is constrained in three degrees of freedom (one translational, two rotational); this squeezes out considerable entropy and thereby facilitates molecular assembly. Compressing a surface layer of these components then can squeeze entropy from the remaining two degrees of translational freedom, and can even provide appreciable activation energy to overcome long-range intermolecular repulsions (e.g., charge-charge interactions among hydrophilic groups). Finally, as the peptoid nanosheet example shows, compression can drive a further assembly or folding process based on solvophobic forces — the same forces that are responsible for most of the stabilization energy of large peptide foldamers, a high-performance polymer for atomically precise nanosytems engineering.
It’s particularly nice that the surface-area cycling that drives the process can be provided by simply shaking the container.
* Richard Bonneau was a founding Rosetta developer.
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Dr Drexler,
Here’s a very interesting paper that just came out, you might want to check it out (in case you haven’t seen it yet): http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000957
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