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.