Designing novel cellulase systems through agent-based modeling and global sensitivity analysis

Apte, Advait; Senger, Ryan S.; Fong, Stephen S.

doi:10.4161/bioe.29160

Cited by 7 publications

(5 citation statements)

References 48 publications

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“…GSA calculates sensitivity as all parameters are varied simultaneously. This method has been used to identify the key operating bottlenecks of kinetic and agent-based models (30,31). Importantly, the predictions made in this research were validated experimentally, and an improved volumetric hydrogen productivity rate was achieved.…”

mentioning

confidence: 88%

High-yield hydrogen production from biomass by in vitro metabolic engineering: Mixed sugars coutilization and kinetic modeling

Rollin

Campo

Myung

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

213

132

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The use of hydrogen (H 2 ) as a fuel offers enhanced energy conversion efficiency and tremendous potential to decrease greenhouse gas emissions, but producing it in a distributed, carbon-neutral, low-cost manner requires new technologies. Herein we demonstrate the complete conversion of glucose and xylose from plant biomass to H 2 and CO 2 based on an in vitro synthetic enzymatic pathway. Glucose and xylose were simultaneously converted to H 2 with a yield of two H 2 per carbon, the maximum possible yield. Parameters of a nonlinear kinetic model were fitted with experimental data using a genetic algorithm, and a global sensitivity analysis was used to identify the enzymes that have the greatest impact on reaction rate and yield. After optimizing enzyme loadings using this model, volumetric H 2 productivity was increased 3-fold to 32 mmol H 2 ·L. The productivity was further enhanced to 54 mmol H 2 ·L −1 ·h −1 by increasing reaction temperature, substrate, and enzyme concentrations-an increase of 67-fold compared with the initial studies using this method. The production of hydrogen from locally produced biomass is a promising means to achieve global green energy production.hydrogen | biomass | in vitro metabolic engineering | metabolic network modeling | global sensitivity analysis

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mentioning

confidence: 88%

High-yield hydrogen production from biomass by in vitro metabolic engineering: Mixed sugars coutilization and kinetic modeling

Rollin

Campo

Myung

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

213

132

View full text Add to dashboard Cite

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“…Today, the range of agent-based model applications is quite broad. For example, these models have been used to represent the Ras-MAPK [17] and NF-kB [38] intracellular signalling pathways, Escherichia coli cytoplasm dynamics [30], bacterial phenotypic switching [46], epithelial host-pathogen interactions [45], cancer systems biology [29], development of restenosis in blood vessels [12], autophagy dynamics and sub-mitochondrial heterogeneity [8], intracellular phosphorus heterogeneity in cultured phytoplankton [16], oxygen metabolism in aerobic-anaerobic respiration [5], and the design of cellulase systems [3].…”

Section: Abm For Biomolecular Modellingmentioning

confidence: 99%

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

Pérez-Rodríguez

Pérez-Pérez

Fdez-Riverola

et al. 2016

Journal of Molecular Graphics and Modelling

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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.

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“…The Epitheliome, a representation of the growth and repair characteristics of epithelial cell populations, is probably one of the earliest applications [ 25 ]. Other more recent applications relate to biofilm formation [ 26 ], bacterial phenotypic switching [ 27 ], cancer development [ 28 , 29 ], bacterial virulence in surgical site infection [ 30 ], the development of restenosis in blood vessels [ 31 ], oxygen metabolism in aerobic-anaerobic respiration [ 32 ], and the design of cellulase systems [ 33 ].…”

Section: Agent-based Models and Their Application In Biologymentioning

confidence: 99%

Agent-Based Spatiotemporal Simulation of Biomolecular Systems within the Open Source MASON Framework

Pérez-Rodríguez

Pérez-Pérez

Glez-Peña

et al. 2015

BioMed Research International

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Agent-based modelling is being used to represent biological systems with increasing frequency and success. This paper presents the implementation of a new tool for biomolecular reaction modelling in the open source Multiagent Simulator of Neighborhoods framework. The rationale behind this new tool is the necessity to describe interactions at the molecular level to be able to grasp emergent and meaningful biological behaviour. We are particularly interested in characterising and quantifying the various effects that facilitate biocatalysis. Enzymes may display high specificity for their substrates and this information is crucial to the engineering and optimisation of bioprocesses. Simulation results demonstrate that molecule distributions, reaction rate parameters, and structural parameters can be adjusted separately in the simulation allowing a comprehensive study of individual effects in the context of realistic cell environments. While higher percentage of collisions with occurrence of reaction increases the affinity of the enzyme to the substrate, a faster reaction (i.e., turnover number) leads to a smaller number of time steps. Slower diffusion rates and molecular crowding (physical hurdles) decrease the collision rate of reactants, hence reducing the reaction rate, as expected. Also, the random distribution of molecules affects the results significantly.

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Designing novel cellulase systems through agent-based modeling and global sensitivity analysis

Cited by 7 publications

References 48 publications

High-yield hydrogen production from biomass by in vitro metabolic engineering: Mixed sugars coutilization and kinetic modeling

High-yield hydrogen production from biomass by in vitro metabolic engineering: Mixed sugars coutilization and kinetic modeling

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

Agent-Based Spatiotemporal Simulation of Biomolecular Systems within the Open Source MASON Framework

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