Consider a short piece of rope: could you guess which knots are more likely to form if you crumple and shake it? Synthetic chemists have long been working on a molecular version of this problem and, so far, have succeeded at synthesizing half a dozen different knots types using molecular self-assembling techniques. But which other knot types will it be possible to realise in the future? This is the challenging question that SISSA scientists, in association with the University of Padua, have tackled using computer simulations in this new work published in Nature Communications. The scientists identified a shortlist, a kind of “periodic table”, of the most designable knot types, i.e. those knots that could easily self-assemble under appropriate physical and chemical conditions. The findings, obtained with computational predictive models, are supported by the latest experimental results and ought to aid the synthesis of as yet undiscovered topologies. This study, and the increasingly predictive capability of molecular modelling techniques, can create novel possible perspectives for future advanced applications, like the construction of sophisticated molecular machines for loading and delivering a nanocargo.