Metabolic network modeling and simulation for drug targeting and discovery

Abstract

Systems biology has greatly contributed toward the analysis and understanding of biological systems under various genotypic and environmental conditions on a much larger scale than ever before. One of the applications of systems biology can be seen in unraveling and understanding complicated human diseases where the primary causes for a disease are often not clear. The in silico genome-scale metabolic network models can be employed for the analysis of diseases and for the discovery of novel drug targets suitable for treating the disease. Also, new antimicrobial targets can be discovered by analyzing, at the systems level, the genome-scale metabolic network of pathogenic microorganisms. Such applications are possible as these genome-scale metabolic network models contain extensive stoichiometric relationships among the metabolites constituting the organism's metabolism and information on the associated biophysical constraints. In this review, we highlight applications of genome-scale metabolic network modeling and simulations in predicting drug targets and designing potential strategies in combating pathogenic infection. Also, the use of metabolic network models in the systematic analysis of several human diseases is examined. Other computational and experimental approaches are discussed to complement the use of metabolic network models in the analysis of biological systems and to facilitate the drug discovery pipeline.

Predicting new molecular targets for rhein using network pharmacology

“…These diagrams can be difficult for a user to explore with currently available network display tools--the networks are often too large, on the order of thousands of nodes, and many tools do not provide biological context to the diagram. The increasing complexity of functional genomics data drives the development of methods and tools for data integration and visualization [14]. …”

Metabolic Associations of Reduced Proliferation and Oxidative Stress in Advanced Breast Cancer

“…CBM metabolic models have been shown to provide an appropriate context for analyzing high-throughput omics datasets and to elucidate the genotype to phenotype relationship (9). The approach has been extensively applied to study the metabolism of various organisms, from microbes (10)(11)(12) to humans (13,14). The potential clinical use of modeling human metabolism has been previously shown across numerous studies, including the identification of hypercholesterolemia drug targets (9), reactions related to hemolytic anemia (9), and metabolic biomarkers of inborn errors of metabolism (15).…”

Network Pharmacology Strategies Toward Multi-Target Anticancer Therapies: From Computational Models to Experimental Design Principles

“…Drugs also influence the metabolism of living cells by targeting enzymes which catalyze metabolic reactions where the metabolite concentrations and fluxes are affected. Therefore, metabolic networks lay down an important foundation for computational tools for disease modeling, and evaluation of metabolites that are perturbed by intended targets has suggested a potential way to drug discovery [98]. In particular, the reconstruction and analysis of system-level metabolic networks allow us to systematically explore the metabolic behavior of cells, and may thus increase the coverage of drug-target identification for cancers.…”