Background: Integrin activation is a critical event in the leukocyte recruitment mechanism controlled by a complex signal transduction network of proteins. The concerted action of these proteins generates a concurrent modular mechanism of regulation characterized both by topological and dynamic properties. Although a qualitative characterization of such a mechanisms is partially available, a quantitative description is lacking, thus limiting the possibility of dynamic modelling of processes. Method: The proposed methodology applies techniques and tools well established in the context of electronics design automation (EDA) for modelling and simulation of such a biochemical system. Event-based simulation is applied, through a hybrid approach, i.e., deterministic and stochastic, to observe the dynamics of variables and to detect the molecular concentrations. EDA assertion-based verification is introduced to describe and synthesize system properties. The simulation is run on parallel CPU/GPU-based clusters.Results: The results show the accuracy of the proposed method to quantitatively observe the system behaviour over the time. Oscillating behaviours and crucial properties to understand the overall dynamics are studied. The monitoring of the on-off, oscillatory, kinetics of integrin by the oscillatory state of ITGB2 between inactive and activate affinity state within 100ms is discussed. Through the property-checking activity, the variable configurations leading to a given number of oscillations and period is given.Conclusion: The proposed computational methodology, aiming to simulate in-silico biochemical network, may represent the ideal complementation to super-resolution microscopy technologies, where molecular dynamics data is generated, but inappropriate mathematical simulation is provided.Keywords : Signal transduction, modelling, simulation.

An Improved Electronic Design Automation Methodology for modelling Leukocyte Integrin Activation

Distefano, Rosario;BOMBIERI, Nicola;Mirenda, Michela;FUMMI, Franco;LAUDANNA, Carlo;GIUGNO, ROSALBA
2015-01-01

Abstract

Background: Integrin activation is a critical event in the leukocyte recruitment mechanism controlled by a complex signal transduction network of proteins. The concerted action of these proteins generates a concurrent modular mechanism of regulation characterized both by topological and dynamic properties. Although a qualitative characterization of such a mechanisms is partially available, a quantitative description is lacking, thus limiting the possibility of dynamic modelling of processes. Method: The proposed methodology applies techniques and tools well established in the context of electronics design automation (EDA) for modelling and simulation of such a biochemical system. Event-based simulation is applied, through a hybrid approach, i.e., deterministic and stochastic, to observe the dynamics of variables and to detect the molecular concentrations. EDA assertion-based verification is introduced to describe and synthesize system properties. The simulation is run on parallel CPU/GPU-based clusters.Results: The results show the accuracy of the proposed method to quantitatively observe the system behaviour over the time. Oscillating behaviours and crucial properties to understand the overall dynamics are studied. The monitoring of the on-off, oscillatory, kinetics of integrin by the oscillatory state of ITGB2 between inactive and activate affinity state within 100ms is discussed. Through the property-checking activity, the variable configurations leading to a given number of oscillations and period is given.Conclusion: The proposed computational methodology, aiming to simulate in-silico biochemical network, may represent the ideal complementation to super-resolution microscopy technologies, where molecular dynamics data is generated, but inappropriate mathematical simulation is provided.Keywords : Signal transduction, modelling, simulation.
2015
EDA, Biological schema
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/940525
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