Integrating systems and structural biology

Modeling at the intersection of systems and structural biology

Here, the focus is on developing workflows to map protein structural information (from PDB) to genome-scale networks of metabolism. We can visualize both networks using interactive mapping algorithms (such as escher) and 3D structures of proteins (using available visual tools). By linking biomacromolecular structures to networks, we can begin to connect biological process that span multiple scales from molecule to organism. 


One application of this workflow is to study the effect that adverse drug reactions (or off-target effects) has on the behavior of entire networks in metabolism, and eventually, the fitness of the organism.


  • Automated pipeline to add protein structural information into genome reconstructions
  • Integration of homology models for reactions with missing crystallographic content
  • Extensive QC/QA of all structures linked to a genome-scale network
  • Minimal structural modifications to revert mutations back to wild-type sequence
  • Reference Publications:
    • Brunk, E. et al. Integrating computational methods to retrofit enzymes to synthetic pathways (2011) Biotechnology and Bioengineering 109 (2), 572-582
    • Guzman, G; Utrilla, J; Nurk, S; Brunk, E; Monk, JM; Ebrahim, A; Palsson, B; Feist, AM.  Model-driven discovery of underground metabolic functions in Escherichia coliPNAS (2015) 112 (3) 929-934
    • Brunk, E*; Mih, N*, Monk, J; Chen, K; Zhang, Z; Bliven, S; O’Brien, E; Chang, RL; Bourne, PE; Palsson, BO. Systems Biology of the Structural Proteome BMC systems biology (2016) DOI: 10.1186/s12918-016-0271-6
    • Mih, N*; Brunk, E*; Bordbar, A; Palsson, BO. The Effect of Single Nucleotide Polymorphisms on Native Metabolite and Drug Responses in Human Erythrocyte Metabolism (2016)  accepted in Plos Comp Bio