Supplementary Material for: Assessing combinatorial diversity of aureochrome bZIPs through genome-wide screening

Aureochromes are unique blue light-responsive LOV (Light Oxygen Voltage) photoreceptors cum basic leucine zipper (bZIP) transcription factors (TFs), present exclusively in photosynthetic marine stramenopiles. Considering the availability of the complete genome sequence, this study focuses on aureochromes from Ectocarpus siliculosus. Aureochromes mediate light-regulated developmental responses in this brown photosynthetic algae. Both the LOV sensor and the bZIP effector shows overall sequence-structure conservation. The structurally similar LOV+bZIP modules of aureochrome homologs/paralogs prefer a dimeric state. Besides a heterogeneous linker connecting the sensor-effector and a flexible N-terminal region, the sequence composition of both domains is vital. Aureochromes execute diverse cellular responses in different photosynthetic stramenopiles – though their activities can vary even within a given algal species. Therefore, it is important to understand whether aureochromes select dimerization partners from the same family or interact with other bZIPs as well. To regulate multifarious biological activities, it is possible that aureochromes activate the global TF interaction network. Following homo/heterodimer modeling, we address the compatibility of dimerization partners by screening through heptad repeats. We evaluate the dimer interface area in terms of gain in solvation energy and the number of hydrogen bonds/salt bridge interactions. We further explore the relative stability of these structures from a graph-theoretic perspective through well-studied measures such as the energy of the graph, average participation coefficient, and betweenness centrality. Furthermore, we also conduct an information-theoretic analysis using hitherto understudied measures such as network information centrality and Kullback-Leibler divergence. We find that all our investigations into the relative stability of the dimers using diverse methods from bioinformatics, network science, and, information theory are in harmonious agreement. Coupling preferences of monomers in aureochromes can be further translated to design novel optogenetic tools useful for understanding human development and disease.