Visualizing mechanistic models by integrating site-specific molecular details into reaction networks

Dan VasilescuJames C SchaffIon MoraruMichael L Blinov^*

• UCONN Health, Farmington, United States

Mechanistic modeling in biology aims to describe biological processes based on details on molecular mechanisms and interactions. Rule-based mechanistic modeling enables the simulation of biological systems while explicitly accounting for molecular details, such as protein domains and their specific interactions. Traditionally, mechanistic models are visually represented by reaction or pathway diagrams that depict transformations and modifications of chemical species. In contrast, rule-based descriptions are effective to encode the detailed specificity of individual interactions (e.g., how phosphorylation at a particular residue affects binding affinity elsewhere in the same protein complex) in a compact and precise form, but are complicated to integrate into comprehensive visual representations. Here, we introduce Molecular Process Diagrams, an approach to embed rule-based specificity directly within reaction network diagrams. Our method highlights three fundamental elements: interacting molecular complexes, molecular sites directly modified by a rule, and molecular sites that modulate but are not directly modified by interactions (e.g., phosphorylation-dependent affinity changes). Implemented at multiple resolution levels within the Virtual Cell (VCell) software, these diagrams maintain pathway-like clarity while accurately reflecting detailed molecular interactions. Additionally, we demonstrate compatibility with Systems Biology Graphical Notation (SBGN) process diagrams, ensuring standardized visual conventions.