Agent-Based Spatiotemporal Simulation of Biomolecular Systems within the Open Source MASON Framework

Abstract

Agent-based modelling is being used to represent biological systems with increasing frequency and success. This paper presents the implementation of a new tool for biomolecular reaction modelling in the open source Multiagent Simulator of Neighborhoods framework. The rationale behind this new tool is the necessity to describe interactions at the molecular level to be able to grasp emergent and meaningful biological behaviour. We are particularly interested in characterising and quantifying the various effects that facilitate biocatalysis. Enzymes may display high specificity for their substrates and this information is crucial to the engineering and optimisation of bioprocesses. Simulation results demonstrate that molecule distributions, reaction rate parameters, and structural parameters can be adjusted separately in the simulation allowing a comprehensive study of individual effects in the context of realistic cell environments. While higher percentage of collisions with occurrence of reaction increases the affinity of the enzyme to the substrate, a faster reaction (i.e., turnover number) leads to a smaller number of time steps. Slower diffusion rates and molecular crowding (physical hurdles) decrease the collision rate of reactants, hence reducing the reaction rate, as expected. Also, the random distribution of molecules affects the results significantly.

Refined Agent Model Using Shape-Based Grained Structure: Application to Membrane Molecules

“…For years, models have been made for each of these interactions separately: molecular dynamics is used for atom-atom interactions [3] or computational models as agent-based systems for enzymatic systems [4] [5]. In this project, we are interested in modeling mitochondria and more particularly, the respiratory chain, a metabolic pathway (enzymatic reaction chain) which takes place inside the inner mitochondrial membrane.…”