Machine learning and molecular design of self-assembling -conjugated oligopeptides

Bryce A. Thurston, Andrew L. Ferguson

Research output: Contribution to journalArticlepeer-review


Self-assembling oligopeptides present a means to fabricate biocompatible supramolecular aggregates with engineered electronic and optical functionality. We conducted molecular dynamics simulations of self-assembling synthetic oligopeptides with Asp-X (Formula presented.) -X (Formula presented.) -X (Formula presented.) - (Formula presented.) -X (Formula presented.) -X (Formula presented.) -X (Formula presented.) -Asp architectures. Dimerisation and trimerisation free energies were computed for a range of Asp-X (Formula presented.) -X (Formula presented.) -X (Formula presented.) amino acid sequences, and for perylenediimide (PDI) and naphthalenediimide (NDI) conjugated (Formula presented.) cores that mediate hydrophobic stacking and electron delocalisation within the self-assembled nanostructure. The larger PDI cores elevated oligomerisation free energies by a factor of 2-3 relative to NDI and also improved alignment of the oligopeptides within the stack. Training of a quantitative structure–property relationship (QSPR) model revealed key physicochemical determinants of the oligomerisation free energies and produced a predictive model for the oligomerisation thermodynamics. Oligopeptides with moderate dimerisation and trimerisation free energies of (Formula presented.) (-25) (Formula presented.) produced aggregates with the best in-register parallel stacking, and we used this criterion within our QSPR model to perform high-throughput virtual screening to identify promising candidates for the spontaneous assembly of ordered nanoaggregates. We identified a small number of oligopeptide candidates for direct testing in large scale molecular simulations, and predict a novel chemistry DAVG-PDI-GVAD previously unstudied by experiment or simulation to produce well-aligned nanoaggregates expected to possess good optical and electronic functionality.

Original languageEnglish (US)
Pages (from-to)930-945
Number of pages16
JournalMolecular Simulation
Issue number11
StatePublished - Jul 24 2018


  • -conjugated oligopeptides
  • molecular dynamics simulation
  • quantitative structure-property relationships
  • self-assembly
  • supramolecular peptides

ASJC Scopus subject areas

  • General Chemistry
  • Information Systems
  • Modeling and Simulation
  • General Chemical Engineering
  • General Materials Science
  • Condensed Matter Physics


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