Molecular networks and system-level properties

Abstract: Molecular systems biology aims to describe the functions of complex biological processes through recursive integration of molecular analysis, modeling, simulation and theory. It focuses on networks that originate from interconnection of genes, proteins and metabolites whose dynamic interactions generate, as an emergent property of the system, the corresponding function. Although evolutionary optimized, intracellular biochemical parameters, such as the expression level of gene products or the affinity between two or more proteins, must have a permissible range that gives robustness against perturbations to the system. Using the yeast G1-to-S transition network as an example we show that sophisticated relations exist among network structure, emergent property and robustness. Different emergent properties are generated from the same network by changing the strength of its interactions, not only by altering expression level, but also through mono and multi-site phosphorylation/dephosphorylation. Besides, multi-site protein phosphorylation modules, widespread in cell cycle, may ensure robust and coherent timing of cell cycle transitions as it happens for the onset of DNA replication. In conclusion, the modulation of biological function/emergent property by modifying interaction strength provides an efficient, highly tunable device to regulate biological processes. Furthermore, the principles outlined herein may provide new insight to network analysis in drug discovery. [Copyright &y& Elsevier]