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

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 omitted.] -X [Formula omitted.] -X [Form...

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Bibliographic Details
Published in:Molecular simulation 2018-07, Vol.44 (11), p.930-945
Main Authors: Thurston, Bryce A., Ferguson, Andrew L.
Format: Article
Language:English
Subjects:
Aggregates
Assembling
Biocompatibility
Computer simulation
Inspection
Machine learning
Mathematical models
Molecular chains
Molecular dynamics
Nondestructive testing
Self-assembly
Stacking
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Summary: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 omitted.] -X [Formula omitted.] -X [Formula omitted.] - [Formula omitted.] -X [Formula omitted.] -X [Formula omitted.] -X [Formula omitted.] -Asp architectures. Dimerisation and trimerisation free energies were computed for a range of Asp-X [Formula omitted.] -X [Formula omitted.] -X [Formula omitted.] amino acid sequences, and for perylenediimide (PDI) and naphthalenediimide (NDI) conjugated [Formula omitted.] 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 omitted.] (-25) [Formula omitted.] 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.
ISSN:0892-7022
1029-0435
DOI:10.1080/08927022.2018.1469754