Optimizing Component–Component Interaction Energies in the Self-Assembly of Finite, Multicomponent Structures

Abstract

Components of multicomponent biological self-assembly processes generally have interfaces that are optimized to enable the process to proceed quickly and reliably. Analogous principles for designing such interfaces for engineered multicomponent self-assembly processes, such as those involving nucleic acid components, are still being developed. Inspired by biological systems, here, we use stochastic kinetic computer simulations to understand how to tune the strength of interfaces to achieve maximal yields in an addressable self-assembly process. We find that high yields of a desired product can be achieved across a broad range of isothermal assembly conditions by appropriately choosing the interaction energies between components and that heterogeneous (i.e., nonuniform) component−component interaction energies can improve self-assembly outcomes, especially because uniform interfacial energies have unusually low assembly rates. In particular, the structures that assemble with the highest yields under isothermal conditions often include a strong−strong− strong−weak interface motif in closed ring substructures. We apply this process for optimizing interfacial energies to a previously characterized set of components for a self-assembly process using measured kinetic and thermodynamic parameters and show that the initial design of the assembling complex could be improved (i.e., made to assemble with higher yield) by 20− 60% using different interface designs. This work suggests that this type of iterative, computational optimization can improve the design cycle for an engineered complex by suggesting next-generation complex designs and preventing the need to experimentally test many different designs.