Abstract
The self-assembly of proteins into protein quaternary structures is of fundamental importance to many biological processes, and protein misassembly is responsible for a wide range of proteopathic diseases. In recent years, abstract lattice models of protein self-assembly have been used to simulate the evolution and assembly of protein quaternary structure, and to provide a tractable way to study the genotype-phenotype map of such systems. Here we generalize these models by representing the interfaces as mutable binary strings. This simple change enables us to model the evolution of interface strengths, interface symmetry, and deterministic assembly pathways. Using the generalized model we are able to reproduce two important results established for real protein complexes: The first is that protein assembly pathways are under evolutionary selection to minimize misassembly. The second is that the assembly pathway of a complex mirrors its evolutionary history, and that both can be derived from the relative strengths of interfaces. These results demonstrate that the generalized lattice model offers a powerful new idealized framework to facilitate the study of protein self-assembly processes and their evolution.
Highlights
IntroductionMany proteins self-assemble into protein quaternary structures, which fulfill a multitude of functions across a wide range of biological processes [1]
Similar knowledge of interactions being preferred to be stronger or weaker can help to predict the evolutionary ancestry of a complex. While these simulations are too idealized to make exact predictions, this general link between ordered pathways in assembly and evolution matches well-established observations that have been made in real protein complexes. This means that our model provides a powerful framework to help study protein complex assembly and evolution
Many proteins self-assemble into protein quaternary structures, which fulfill a multitude of functions across a wide range of biological processes [1]
Summary
Many proteins self-assemble into protein quaternary structures, which fulfill a multitude of functions across a wide range of biological processes [1]. A general class of polyomino tile selfassembly models have strong analytic potential while maintaining semblance to protein quatenary structure and retaining qualitative realism. The same model was developed and expanded with evolutionary dynamics by Johnston et al [3], and used to probe general properties of genotype-phenotype maps by Greenbury et al [4]. We develop a generalization of interactions using binary strings in these polyomino assembly models, in particular introducing variable binding strengths and relaxing the rejection of misassembly. While our binary interface polyomino self-assembly model does not account for the variety of amino acids and their particular properties, it provides a reasonable coarse-grained approach. Similar models of protein interactions using binary subunit interfaces have linked protein-protein interaction properties to experimental observations on protein family evolution [7, 8]
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