Simulating biological processes: stochastic physics from whole cells to colonies

Earnest, Tyler M.; Cole, John A.; Luthey‐Schulten, Zaida

doi:10.1088/1361-6633/aaae2c

Cited by 29 publications

(35 citation statements)

References 244 publications

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“…Therefore, the effective rate constant (5) can also be written in terms of the total rebinding probability:…”

Section: A Irreversible Bimolecular Diffusion-influenced Reaction In mentioning

confidence: 99%

“…Table (1) shows the simulated and the expected theoretical values for n ∈ [1,5] steps. The simulation results agree well with the expected values, with discrepancies never exceeding 0.1%.…”

Section: A Numerical Validation Of Mlm Theory 1 Rebinding Probabilitymentioning

confidence: 99%

“…In the intracellular environment, macromolecules can be heterogeneously distributed in space and react stochastically at low concentrations. The conventional mass action-based approach is insufficient to describe the reaction-diffusion (RD) behavior of the macromolecules and thus, it is necessary to incorporate space and stochasticity into the model [1][2][3][4][5][6]. Generally, we can represent space as a continuum (off-lattice) or a discretized lattice model.…”

Section: Introductionmentioning

confidence: 99%

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Reaction-diffusion kinetics on lattice at the microscopic scale

et al. 2018

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Lattice-based stochastic simulators are commonly used to study biological reaction-diffusion processes. Some of these schemes that are based on the reaction-diffusion master equation (RDME), can simulate for extended spatial and temporal scales but cannot directly account for the microscopic effects in the cell such as volume exclusion and diffusion-influenced reactions. Nonetheless, schemes based on the high-resolution microscopic lattice method (MLM) can directly simulate these effects by representing each finite-sized molecule explicitly as a random walker on fine lattice voxels. The theory and consistency of MLM in simulating diffusion-influenced reactions have not been clarified in detail. Here, we examine MLM in solving diffusion-influenced reactions in 3D space by employing the Spatiocyte simulation scheme. Applying the random walk theory, we construct the general theoretical framework underlying the method and obtain analytical expressions for the total rebinding probability and the effective reaction rate. By matching Collins-Kimball and lattice-based rate constants, we obtained the exact expressions to determine the reaction acceptance probability and voxel size. We found that the size of voxel should be about 2% larger than the molecule. The theoretical framework of MLM is validated by numerical simulations, showing good agreement with the off-lattice particle-based method, eGFRD. MLM run time is more than an order of magnitude faster than eGFRD when diffusing macromolecules with typical concentrations observed in the cell. MLM also showed good agreements with eGFRD and mean-field models in case studies of two basic motifs of intracellular signaling, the protein production-degradation process and the dual phosphorylation-dephosphorylation cycle. In addition, when a reaction compartment is populated with volume-excluding obstacles, MLM captures the non-classical reaction kinetics caused by anomalous diffusion of reacting molecules.

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“…Therefore, the effective rate constant (5) can also be written in terms of the total rebinding probability:…”

Section: A Irreversible Bimolecular Diffusion-influenced Reaction In mentioning

confidence: 99%

Section: A Numerical Validation Of Mlm Theory 1 Rebinding Probabilitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reaction-diffusion kinetics on lattice at the microscopic scale

et al. 2018

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“…Thus, randomness can be useful for modeling systems and engineered control of systems (Brandao et al, 2016). In particular, stochasticity can be augmented with atomic-scale molecular modeling approaches (Earnest et al, 2018).…”

Section: Randomness In Biological Functionsmentioning

confidence: 99%

Order Through Disorder: The Characteristic Variability of Systems

Ilan

2020

Front. Cell Dev. Biol.

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Randomness characterizes many processes in nature, and therefore its importance cannot be overstated. In the present study, we investigate examples of randomness found in various fields, to underlie its fundamental processes. The fields we address include physics, chemistry, biology (biological systems from genes to whole organs), medicine, and environmental science. Through the chosen examples, we explore the seemingly paradoxical nature of life and demonstrate that randomness is preferred under specific conditions. Furthermore, under certain conditions, promoting or making use of variability-associated parameters may be necessary for improving the function of processes and systems.

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“…The choice of spatial simulators largely depends on the timescale and spatial resolution of the system of interest [8][9][10][11][12][13]. For example, high-performance molecular dynamics (MD) simulators [14] can accurately capture the atomistic behavior of up to several macromolecules in a system but are limited in their timescale, allowing only simulations for up to a few milliseconds [15,16].…”

Section: Introductionmentioning

confidence: 99%

pSpatiocyte: a high-performance simulator for intracellular reaction-diffusion systems

Arjunan

Miyauchi

Iwamoto

et al. 2019

Preprint

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Background: Studies using quantitative experimental methods have shown that intracellular spatial distribution of molecules plays a central role in many cellular systems. Spatially resolved computer simulations can integrate quantitative data from these experiments to construct physically accurate models of the systems. Although computationally expensive, microscopic resolution reaction-diffusion simulators, such as Spatiocyte can directly capture intracellular effects comprising diffusion-limited reactions and volume exclusion from crowded molecules by explicitly representing individual diffusing molecules in space. To alleviate the steep computational cost typically associated with the simulation of large or crowded intracellular compartments, we present a parallelized Spatiocyte method called pSpatiocyte. Results: The new high-performance method employs unique parallelization schemes on hexagonal close-packed (HCP) lattice to efficiently exploit the resources of common workstations and large distributed memory parallel computers. We introduce a coordinate system for fast accesses to HCP lattice voxels, a parallelized event scheduler, a parallelized Gillespie's direct-method for unimolecular reactions, and a parallelized event for diffusion and bimolecular reaction processes. We verified the correctness of pSpatiocyte reaction and diffusion processes by comparison to theory. To evaluate the performance of pSpatiocyte, we performed a series of parallelized diffusion runs on the RIKEN K computer. In the case of fine lattice discretization with low voxel occupancy, pSpatiocyte exhibited 74% parallel efficiency and achieved a speedup of 7686 times with 663552 cores compared to the runtime with 64 cores. In the weak scaling performance, pSpatiocyte obtained efficiencies of at least 60% with up to 663552 cores. When executing the Michaelis-Menten benchmark model on an eight-core workstation, pSpatiocyte required 45-and 55-fold shorter runtimes than Smoldyn and the parallel version of ReaDDy, respectively. As a high-performance application example, we study the dual phosphorylation-dephosphorylation cycle of the MAPK system, a typical reaction network motif in cell signaling pathways. Conclusions: pSpatiocyte demonstrates good accuracies, fast runtimes and a significant performance advantage over well-known microscopic particle simulators for large-scale simulations of intracellular reaction-diffusion systems. The source code of pSpatiocyte is available at https://spatiocyte.org.

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Simulating biological processes: stochastic physics from whole cells to colonies

Cited by 29 publications

References 244 publications

Reaction-diffusion kinetics on lattice at the microscopic scale

Reaction-diffusion kinetics on lattice at the microscopic scale

Order Through Disorder: The Characteristic Variability of Systems

pSpatiocyte: a high-performance simulator for intracellular reaction-diffusion systems

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