Systems biology of the structural proteome

Area of Science:

• Systems Biology
• Structural Biology
• Computational Biology

Background:

• Genome-scale models (GEMs) are foundational for understanding organism-specific metabolic, protein synthesis, and regulatory networks.
• Integrating protein structural information into GEMs expands systems biology research into structural systems biology and systems pharmacology.
• Current GEMs provide a structured knowledge base for computational biological studies.

Purpose of the Study:

• To present the generation, application, and dissemination of genome-scale models with protein structures (GEM-PRO).
• To demonstrate the utility of integrating molecular-scale analyses with systems biology approaches.
• To provide resources and tutorials for linking protein information to GEMs.

Main Methods:

• Development of genome-scale models incorporating protein structural data (GEM-PRO).
• Comparative analyses of temperature-dependent growth, protein fold families, substrate specificity, and proteome features.
• Utilizing a public GitHub repository for dissemination and tutorials.

Main Results:

• GEM-PRO models were generated for Escherichia coli and Thermotoga maritima.
• Integration of molecular and systems biology approaches revealed insights into temperature effects on growth and protein distributions.
• Comparative analyses highlighted characteristic features of whole-cell proteomes.

Conclusions:

• GEM-PRO provides a direct link from genotype to phenotypic function through structured protein information.
• Integrating protein structural properties enhances the modeling and prediction of cellular phenotypes and comparative systems biology.
• GEM-PRO offers insights into the physical embodiment of genotype and aids in exploring organismal adaptive strategies.