Self-assembly at the multi-scale level: challenges and new avenues for inspired synthetic biology modelling

We describe here progresses in the field of molecular simulations of large, macromolecular assemblies of different nature, ranging from protein complexes to protein–lipids, virus-like particles and interfaces with inorganic and organic substrates. We selected systems that are particularly interesting for the field of Synthetic Biology in the sense that they embed crucial chemical and biological functions that can inspire the design of simplified assemblies for application in nanotechnology, cell biology and biomedicine. These systems pose multiple challenges for simulations because of their need in accurate physical description of the variables playing a role in the realistic description of the molecular interactions occurring in the self-assembling process. In particular, the need for more sophisticated and flexible force fields for the study of complex anisotropic systems undergoing conformational changes during assembly is discussed. We highlight the importance of learning from accurate first-principle atomistic simulations in the development of multiscale and mixed approaches for a unified theoretical approach to such a vast repertoire of applications. In the future, such flexible and multi-tasking efficient simulation approaches will allow to routinely study large systems and their crucial functional mechanisms to be exploited in Synthetic Biology.