Smoldyn

Category Cross-Omics>Agent-Based Modeling/Simulation/Tools

Abstract Smoldyn is a computer program for cell-scale biochemical simulations. It simulates each molecule of interest individually to capture natural stochasticity and for nanometer-scale spatial resolution.

It treats other molecules implicitly, so it can simulate tens of thousands of molecules over several minutes of real time. Simulated molecules diffuse, react, are confined by surfaces, and bind to membranes much as they would in a real biological system.

Smoldyn is also considered a particle-based "spatial stochastic simulator for chemical reaction networks." Molecules diffuse by Brownian motion, reactions occur when reactants collide, and molecules interact with surfaces in realistic ways, including reflection, adsorption, transmission, or desorption.

These capabilities make Smoldyn useful for investigating topics such as:

1) Reactions and diffusion within spatially crowded compartments;

2) “Hop diffusion” of lipids in biochemical membranes;

3) Cell signaling, whether by neurotransmitters or messenger proteins; and

4) Quantification of Fluorescence Recovery After Photobleaching (FRAP) experiments.

To run a Smoldyn simulation, you need to describe your model in a plain-text configuration file. This file describes the system surfaces, molecular species, diffusion coefficients and chemical reactions. It also lists parameters for the graphical display and any quantitative output.

Smoldyn reads this file, sets up simulation parameters, and runs the simulation. During the simulation, it displays the system via a graphics window and saves quantitative data to text files.

Smoldyn features/capabilities include:

1) Molecular diffusion --

Isotropic - simple Brownian motion that obeys Fick's laws;

Anisotropic - partially oriented diffusion, which might apply to liquid crystals or within zeolites;

Drift - diffusion with net motion, to represent external forces on molecules; and

Surface - surface-bound molecules (e.g. integral membrane proteins) can diffuse within the surface.

2) Chemical reactions --

Zeroth order - adds molecules to the system from un-modeled processes (e.g. protein synthesis);

Unimolecular - dissociation reactions or conversions between molecular conformations;

Bimolecular - association or other second order chemical reactions;

Surface-specific - reactions can be defined to only occur on a specific surface;

Compartment-specific - reactions can be defined to only occur in a specific compartment;

Conformational spread - for transmission of protein activity through mechanical interactions; and

Excluded volume - with special reactions, molecules reflect off of each other to simulate excluded volume.

3) Surfaces --

Six (6) elementary shapes - surfaces can be constructed from rectangles, triangles, spheres, hemispheres, cylinders, or disks, which allows for convenient input;

Four (4) surface molecule orientations - molecules can bind to the front or back of a surface (e.g. peripheral membrane protein) or can be transmembrane in an “up” or “down” orientation;

Adsorption and desorption - molecules adsorb to and desorb from surfaces with quantitatively accurate rates;

Partial transmission - surfaces can be partially permeable to specific molecules, with accurate permeability coefficients; and

Compartments - spatial compartments, which are particularly useful for input and output, can be defined using surfaces.

4) User interface and support --

Installation - relatively simple; full instructions are included in the user manual;

Graphics - displayed while the simulation executes, but can also be turned off for faster simulations;

Configuration files - user can write files in plain text using relatively simple statements; and

Documentation - Smoldyn has a thorough 88 page user manual and a 93 page programmers manual.

Support - E-mail steven.s.andrews@gmail.com with questions.

Smoldyn's Accuracy --

According to the manufacturer quantitative accuracy is one of Smoldyn’s particular strengths. This means that Smoldyn simulates chemical reactions and molecule-surface interactions at the rates that the user specified in his or her configuration file.

A consequence of this accuracy is that Smoldyn simulates ‘chemical equilibria’ with the correct concentrations.

Quantitative accuracy is important for several reasons:

1) The qualitative dynamics of a system can be highly sensitive to individual rate constants;

2) Results from algorithms that are known to be inaccurate can be inconclusive;

3) Accurate simulations can be useful tools for quantifying experimental measurements; and

4) More accurate algorithms allow longer simulation time steps, and thus faster simulations.

Quantitative accuracy is surprisingly difficult to achieve for particle-based simulation, such as that performed by Smoldyn.

Whereas mass-action simulators (e.g. COPASI - see G6G Abstract Number 20296) can benefit from literally centuries of research on efficient and accurate numerical methods for solving ordinary differential equations (ODEs), only a handful of papers have been published on ‘accurate particle-based simulation’ methods.

One of these papers (Andrews and Bray, 2004) presents the chemical reaction algorithms on which Smoldyn is based.

Another paper, (Accurate particle-based simulation of adsorption, desorption and partial transmission, Steven S Andrews 2009 Phys. Biol. 6: 046015), presents the molecule-surface interactions that Smoldyn implements.

These investigations account for the fact that chemical reactions and adsorption to surfaces necessarily affect the distributions of molecules.

Other particle-based simulators [MCell - see G6G Abstract Number 20620 and ChemCell] do Not account for this fact, but instead use a mean-field approximation for chemical concentrations.

Utility programs --

Two (2) utility programs are distributed with Smoldyn: wrl2smol and SmolCrowd. According to the manufacturer these programs are Not as user-friendly as the Smoldyn program, but still may be useful for end-users:

1) wrl2smol - wrl2smol reads Virtual Reality Modeling Language (VRML) format triangle mesh data, which can be written by most mesh-generation programs, and converts it to Smoldyn format surface data.

This allows users to use experimental surface data in Smoldyn simulations.

2) SmolCrowd - SmolCrowd creates lists of randomly placed circles or spheres, output in Smoldyn format, for use in crowding simulations.

These crowders, which do Not overlap each other, can all be the same size, or can be chosen from a power-law size distribution. The crowders can be placed in ways that account for periodic boundaries.

System Requirements

Contact manufacturer.

Manufacturer

Manufacturer Web Site Smoldyn

Price Contact manufacturer.

G6G Abstract Number 20619

G6G Manufacturer Number 104220