Understanding and predicting the transition of one-dimensional information into three-dimensional information is the key to resolving the protein folding problem. Elucidating the role of evolutionarily conserved features in proteins can provide significant insight into this process. Here we report the identification of a conserved long-range interaction network within our model protein system, which we propose governs protein folding, dynamics and stability through the generation of the topology. This system consists of twenty-eight proteins which belong to three superfamilies: the all beta-sheet immunoglobulins, the mixed alpha/beta-plaits and the all alpha-helical death domains. Despite differences in sequence, function and secondary structure composition, these three groups share a common polypeptide chain length and Greek-key topology. The role of the conserved long-range interaction network in governing topology, stability and energetics was studied using macromolecular simulations (molecular dynamics and simulated annealing) and the application of network science (diameter, fragmentation, giant clusters and betweeness-centrality). In the nine select protein structures analyzed by these computational approaches, three from each superfamily, we find that preferentially, the conserved long-range interactions are the most thermodynamically stable and play a significant role in governing both the formation and dynamics of the network. These results will be presented.

Conserved long-range interaction networks, energetics and the determinants of protein topology

2019 Spring National Meeting

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