PT  - JOURNAL ARTICLE
AU  - Forster, Joel C.
AU  - Krausser, Johannes
AU  - Vuyyuru, Manish R.
AU  - Baum, Buzz
AU  - Šarić, Anđela
TI  - Designing membrane-reshaping nanostructures through artificial evolution
AID  - 10.1101/2020.02.27.968149
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.27.968149
4099  - http://biorxiv.org/content/early/2020/02/28/2020.02.27.968149.short
4100  - http://biorxiv.org/content/early/2020/02/28/2020.02.27.968149.full
AB  - In this paper we combine the rules of natural evolution with molecular dynamics simulations to design a nanostructure with a desired function. We apply this scheme to the case of a ligand-covered nanoparticle and evolve ligand patterns that promote efficient cell uptake. Surprisingly, we find that in the regime of low ligand number the fittest structures are characterised by ligands arranged into long one-dimensional chains that pattern the surface of the particle. We show that these chains of ligands provide particles with high rotational freedom and they lower the free energy barrier for membrane crossing. This demonstrates the efficacy of artificial evolution to identify non-intuitive design rules and reveals a new principle of design that can be used to inform artificial nanoparticle construction and the search for inhibitors of viral entry.