Molecular Design of a Minimal Peptide Nanoparticle

Raja Dey, Yan Xia, Mu Ping Nieh, Peter Burkhard

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Nanoparticles are getting a great deal of attention in the rapidly developing field of nanomedicine. For example they can be used as drug delivery systems, for imaging applications, or as carriers for synthetic vaccines. Protein-based nanoparticles offer the advantage of biocompatibility and biodegradability thus avoiding some of the major toxicity concerns with nanoparticle associated approaches. Our group has developed self-assembling peptide/protein nanopartices (SAPNs) that are built up from two coiled-coil oligomerization domains joined by a linker region and used them to design subunit vaccines. For drug delivery approaches the SAPNs need to be as small as possible to avoid strong immune responses that could possibly even lead to anaphylaxis. Here we used a computational and biophysical approach to minimize the size of the SAPNs for their use as drug delivery system. We tested different charge distributions on the pentameric and trimeric coiled-coils in silico with molecular dynamics simulations to down-select an optimal design. This design was then investigated in vitro by biophysical methods and we were able to engineer a minimal SAPN of only 11 nm in diameter. Such minimal-sized SAPNs offer new avenues for a safer development as drug delivery systems or other biomedical applications.

Original languageEnglish (US)
Pages (from-to)724-732
Number of pages9
JournalACS Biomaterials Science and Engineering
Issue number5
StatePublished - May 8 2017
Externally publishedYes

Bibliographical note

Funding Information:
Support by the NIH/NIDA (award 1DP1DA033524) and the NIH/NIGMS (award 1P01GM096971) to P.B. for this work is gratefully acknowledged. M.-P.N. and Y.X. thank the NSF-MRI support for the acquisition of SAXS instrument (NSF DMR 1228817) enabling the structural characterization.

Publisher Copyright:
© 2016 American Chemical Society.


  • drug delivery
  • molecular dynamics simulation
  • peptide nanoparticle
  • protein design
  • self-assembly


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