High performance computing for three-dimensional agent-based molecular models
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Introduction and motivation
New advances in super-resolution and super-localisation techniques have allowed experimental molecular biophysics and biochemistry to go beyond ensemble measurements and obtain data at the single molecule level [4], [15]. Such experiments are able to track down key motions, reactions, and interactions of individual molecules with high temporal and spatial resolution. However, the acquisition of such data is very time-consuming, partially because the techniques are not yet advanced enough to
Related work: existing approaches for biomolecular modelling and simulation
Agent-based models (ABM) are a well-known and favoured modelling strategy for biomolecular systems [7]. Generically, these models are composed by a population of heterogeneous agents, which represent the molecules under study, including their shape, size and interaction logic. Biomolecular events unfold on an explicit and specific environment (e.g. representing the cytoplasmic environment) where agents act autonomously, executing some sort of itinerary (e.g. molecular diffusion). Each agent
High performance approaches for three-dimensional agent-based biomolecular simulation
Generally, a three-dimensional model simulated at the molecular level should describe: the volume, shape, localisation, direction vector and speed of each molecule; the rules of interaction between molecules; and, the volume of the environment (e.g. the cytoplasm, a growth volume, or the cell).
Therefore, the implementation of our biomolecular model in MASON entailed the definition of common biophysics and biochemical laws and assumptions. More specifically, our model accounts for molecular
Results and discussion
The simulation of the enzymatic activity of 2-hydroxymuconate tautomerase (EC 5.3.2.6) was used to compare the proposed approaches. The three-dimensional continuous environment was dimensioned for a volume of 0.48 μm3. Table 1 details molecule characteristics, namely dimensions (i.e. molecular weight and radius), rate of movement (molecular diffusion) and number (concentration). The enzyme is also characterised by the kinetic parameters Km and kcat. Further details on this enzyme and its
Conclusions and further work
Arguably, three-dimensional continuous simulations of the interplay of individual molecules are among the most demanding in silico simulations. The modelling of realistic cellular scenarios can easily encompass thousands of agents and the time scale to monitor the interplay can easily go from seconds to nanoseconds. Existing high performance individual particle approaches majorly rely on specialised computing architectures and highly specialised programming. Therefore, these approaches have a
Acknowledgments
This work was partially funded by the [14VI05] Contract-Programme from the University of Vigo and the Agrupamento INBIOMED from DXPCTSUG-FEDER unha maneira de facer Europa (2012/273). The research leading to these results has received funding from the European Union’s Seventh Framework Programme FP7/REGPOT-2012-2013.1 under grant agreement n°316265, BIOCAPS. This document reflects only the author’s views and the European Union is not liable for any use that may be made of the information
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