High performance computing for three-dimensional agent-based molecular models

https://doi.org/10.1016/j.jmgm.2016.06.001Get rights and content

Highlights

  • Agent-based simulations are increasingly popular in exploring and understanding cellular systems.

  • Molecular models are computationally demanding but are crucial to study key cellular phenomena such as molecular crowding.

  • The proposed agent-based approaches contribute to high performance three-dimensional molecular simulation.

  • Our approaches may be implemented in typical Life Sciences research centres and do not require specialised computing skills.

  • Our approaches may be applied to any model at molecular level and have the potential of being used in any agent-based tool.

Abstract

Agent-based simulations are increasingly popular in exploring and understanding cellular systems, but the natural complexity of these systems and the desire to grasp different modelling levels demand cost-effective simulation strategies and tools.

In this context, the present paper introduces novel sequential and distributed approaches for the three-dimensional agent-based simulation of individual molecules in cellular events. These approaches are able to describe the dimensions and position of the molecules with high accuracy and thus, study the critical effect of spatial distribution on cellular events. Moreover, two of the approaches allow multi-thread high performance simulations, distributing the three-dimensional model in a platform independent and computationally efficient way.

Evaluation addressed the reproduction of molecular scenarios and different scalability aspects of agent creation and agent interaction. The three approaches simulate common biophysical and biochemical laws faithfully. The distributed approaches show improved performance when dealing with large agent populations while the sequential approach is better suited for small to medium size agent populations.

Overall, the main new contribution of the approaches is the ability to simulate three-dimensional agent-based models at the molecular level with reduced implementation effort and moderate-level computational capacity. Since these approaches have a generic design, they have the major potential of being used in any event-driven agent-based tool.

Section snippets

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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