Dataset Information

SpringSaLaD: A Spatial, Particle-Based Biochemical Simulation Platform with Excluded Volume.

ABSTRACT: We introduce Springs, Sites, and Langevin Dynamics (SpringSaLaD), a comprehensive software platform for spatial, stochastic, particle-based modeling of biochemical systems. SpringSaLaD models biomolecules in a coarse-grained manner as a group of linked spherical sites with excluded volume. This mesoscopic approach bridges the gap between highly detailed molecular dynamics simulations and the various methods used to study network kinetics and diffusion at the cellular level. SpringSaLaD is a standalone tool that supports model building, simulation, visualization, and data analysis, all through a user-friendly graphical user interface that should make it more accessible than tools built into more comprehensive molecular dynamics infrastructures. Importantly, for bimolecular reactions we derive an exact expression relating the macroscopic on-rate to the various microscopic parameters with the inclusion of excluded volume; this makes SpringSaLaD more accurate than other tools, which rely on approximate relationships between these parameters.

SUBMITTER: Michalski PJ

PROVIDER: S-EPMC4744174 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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SpringSaLaD: A Spatial, Particle-Based Biochemical Simulation Platform with Excluded Volume.

Michalski Paul J PJ Loew Leslie M LM

Biophysical journal 20160201 3

We introduce Springs, Sites, and Langevin Dynamics (SpringSaLaD), a comprehensive software platform for spatial, stochastic, particle-based modeling of biochemical systems. SpringSaLaD models biomolecules in a coarse-grained manner as a group of linked spherical sites with excluded volume. This mesoscopic approach bridges the gap between highly detailed molecular dynamics simulations and the various methods used to study network kinetics and diffusion at the cellular level. SpringSaLaD is a stan ...[more]

PMID: 26840718

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Project description:Detailed modeling and simulation of biochemical systems is complicated by the problem of combinatorial complexity, an explosion in the number of species and reactions due to myriad protein-protein interactions and post-translational modifications. Rule-based modeling overcomes this problem by representing molecules as structured objects and encoding their interactions as pattern-based rules. This greatly simplifies the process of model specification, avoiding the tedious and error prone task of manually enumerating all species and reactions that can potentially exist in a system. From a simulation perspective, rule-based models can be expanded algorithmically into fully-enumerated reaction networks and simulated using a variety of network-based simulation methods, such as ordinary differential equations or Gillespie's algorithm, provided that the network is not exceedingly large. Alternatively, rule-based models can be simulated directly using particle-based kinetic Monte Carlo methods. This "network-free" approach produces exact stochastic trajectories with a computational cost that is independent of network size. However, memory and run time costs increase with the number of particles, limiting the size of system that can be feasibly simulated. Here, we present a hybrid particle/population simulation method that combines the best attributes of both the network-based and network-free approaches. The method takes as input a rule-based model and a user-specified subset of species to treat as population variables rather than as particles. The model is then transformed by a process of "partial network expansion" into a dynamically equivalent form that can be simulated using a population-adapted network-free simulator. The transformation method has been implemented within the open-source rule-based modeling platform BioNetGen, and resulting hybrid models can be simulated using the particle-based simulator NFsim. Performance tests show that significant memory savings can be achieved using the new approach and a monetary cost analysis provides a practical measure of its utility.

Project description:BackgroundTo study cell biological phenomena which depend on diffusion, active transport processes, or the locations of species, modeling and simulation studies need to take space into account. To describe the system as a collection of discrete objects moving and interacting in continuous space, various particle-based reaction diffusion simulators for cell-biological system have been developed. So far the focus has been on particles as solid spheres or points. However, spatial dynamics might happen at different organizational levels, such as proteins, vesicles or cells with interrelated dynamics which requires spatial approaches that take this multi-levelness of cell biological systems into account.ResultsBased on the perception of particles forming hollow spheres, ML-Force contributes to the family of particle-based simulation approaches: in addition to excluded volumes and forces, it also supports compartmental dynamics and relating dynamics between different organizational levels explicitly. Thereby, compartmental dynamics, e.g., particles entering and leaving other particles, and bimolecular reactions are modeled using pair-wise potentials (forces) and the Langevin equation. In addition, forces that act independently of other particles can be applied to direct the movement of particles. Attributes and the possibility to define arbitrary functions on particles, their attributes and content, to determine the results and kinetics of reactions add to the expressiveness of ML-Force. Its implementation comprises a rudimentary rule-based embedded domain-specific modeling language for specifying models and a simulator for executing models continuously. Applications inspired by cell biological models from literature, such as vesicle transport or yeast growth, show the value of the realized features. They facilitate capturing more complex spatial dynamics, such as the fission of compartments or the directed movement of particles, and enable the integration of non-spatial intra-compartmental dynamics as stochastic events.ConclusionsBy handling all dynamics based on potentials (forces) and the Langevin equation, compartmental dynamics, such as dynamic nesting, fusion and fission of compartmental structures are handled continuously and are seamlessly integrated with traditional particle-based reaction-diffusion dynamics within the cell. Thereby, attributes and arbitrary functions allow to flexibly describe diverse spatial phenomena, and relate dynamics across organizational levels. Also they prove crucial in modeling intra-cellular or intra-compartmental dynamics in a non-spatial manner, and, thus, to abstract from spatial dynamics, on demand which increases the range of multi-compartmental processes that can be captured.

Dataset Information

SpringSaLaD: A Spatial, Particle-Based Biochemical Simulation Platform with Excluded Volume.

Publications

SpringSaLaD: A Spatial, Particle-Based Biochemical Simulation Platform with Excluded Volume.

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