Optimizing self-assembly pathways using insights from coarse-grained models
William M. Jacobs, Princeton

Both the self-assembly of DNA nanostructures and the folding of large proteins can be dramatically slowed by mis-interactions that lead to kinetic trapping.  However, kinetic trapping can often be avoided by optimizing a time-dependent protocol for guiding the self-assembly reaction.  Using a coarse-grained model of multicomponent self-assembly, our work has demonstrated how quasi-equilibrium protocols can be designed or rationalized in various molecular systems.  In the case of DNA nanostructures, we showed that implementing a hierarchical assembly pathway substantially improves the final yield of correctly formed structures by modifying the critical nucleus that is required to initiate structure growth.  Then, in an analysis of large globular proteins, we found that step-wise folding pathways explain a significant fraction of evolutionarily conserved variations in protein translation rates.  These insights suggest practical design rules for improving the speed and accuracy of self-assembly in biomolecular and colloidal systems where the interactions between subunits can be programmed.