Visualization of signal transduction processes in the crowded environment of the cell

Falk, Martin; Klann, Michael; Reuß, Matthias; Ertl, Thomas

doi:10.1109/pacificvis.2009.4906853

Cited by 22 publications

(23 citation statements)

References 14 publications

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“…The resulting detailed in silico cell can also be visualized by advanced and interactive visualization tools, thus providing a powerful virtual microscope [13,47,48]. …”

Section: Discussionmentioning

confidence: 99%

Agent-based simulation of reactions in the crowded and structured intracellular environment: Influence of mobility and location of the reactants

Klann

Lapin

Reuß

2011

BMC Systems Biology

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BackgroundIn this paper we apply a novel agent-based simulation method in order to model intracellular reactions in detail. The simulations are performed within a virtual cytoskeleton enriched with further crowding elements, which allows the analysis of molecular crowding effects on intracellular diffusion and reaction rates. The cytoskeleton network leads to a reduction in the mobility of molecules. Molecules can also unspecifically bind to membranes or the cytoskeleton affecting (i) the fraction of unbound molecules in the cytosol and (ii) furthermore reducing the mobility. Binding of molecules to intracellular structures or scaffolds can in turn lead to a microcompartmentalization of the cell. Especially the formation of enzyme complexes promoting metabolic channeling, e.g. in glycolysis, depends on the co-localization of the proteins.ResultsWhile the co-localization of enzymes leads to faster reaction rates, the reduced mobility decreases the collision rate of reactants, hence reducing the reaction rate, as expected. This effect is most prominent in diffusion limited reactions. Furthermore, anomalous diffusion can occur due to molecular crowding in the cell. In the context of diffusion controlled reactions, anomalous diffusion leads to fractal reaction kinetics. The simulation framework is used to quantify and separate the effects originating from molecular crowding or the reduced mobility of the reactants. We were able to define three factors which describe the effective reaction rate, namely f diff for the diffusion effect, f volume for the crowding, and f access for the reduced accessibility of the molecules.ConclusionsMolecule distributions, reaction rate constants and structural parameters can be adjusted separately in the simulation allowing a comprehensive study of individual effects in the context of a realistic cell environment. As such, the present simulation can help to bridge the gap between in vivo and in vitro kinetics.

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“…The resulting detailed in silico cell can also be visualized by advanced and interactive visualization tools, thus providing a powerful virtual microscope [13,47,48]. …”

Section: Discussionmentioning

confidence: 99%

Agent-based simulation of reactions in the crowded and structured intracellular environment: Influence of mobility and location of the reactants

Klann

Lapin

Reuß

2011

BMC Systems Biology

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“…Thus, a lot of effort has been undertaken in order to reduce the involved polygon count and thus enable interactive visualization of complex molecular models. The proposed algorithms span a wide range of underlying concepts, such as level-of-detail [29,32,38], impostors and glyphs [40,51,3,15,11] or geometric instancing [10,33]. Often, geometry or tessellation shaders, provided by modern GPUs, are also exploited to create spherical or ribbon-based representations of molecules [27,52,21].…”

Section: Related Workmentioning

confidence: 99%

“…Many researchers have also focused on the molecule scale. For instance, Falk et al visualize molecule reactions by means of arrows augmenting paths representing molecule trajectories [10]. Grottel et al on the other hand focus on the molecular surface and visualize electrostatic dipoles through color overlaid on the surface [13].…”

Section: Related Workmentioning

confidence: 99%

Physics-Based Visual Characterization of Molecular Interaction Forces

Hermosilla

Estrada

Guallar

et al. 2017

IEEE Trans. Visual. Comput. Graphics

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Fig. 1. Successive steps during the visual analysis of the binding nature of Aspirin and the Phospholipase A2 protein. We compute and visualize all essential interaction energies represented by 2D and 3D arrows. The orientation of the depicted arrows encodes the sign of the energy, i.e., attracting vs. repelling force. The width of the arrows as well as the color of the residue's silhouettes support energy quantification. During the visual analysis, energies are computed and depicted on-the-fly to support interactive hypothesis testing (left), and residues can be filtered based on energy and distance to obtain a more focused view (middle). Additionally, a 2D visualization helps to obtain total energy values in an uncluttered manner (right).Abstract-Molecular simulations are used in many areas of biotechnology, such as drug design and enzyme engineering. Despite the development of automatic computational protocols, analysis of molecular interactions is still a major aspect where human comprehension and intuition are key to accelerate, analyze, and propose modifications to the molecule of interest. Most visualization algorithms help the users by providing an accurate depiction of the spatial arrangement: the atoms involved in inter-molecular contacts. There are few tools that provide visual information on the forces governing molecular docking. Unfortunately these tools, commonly restricted to close interaction between atoms, do not consider whole simulation paths, long-range distances and, importantly, do not provide visual cues for a quicker and intuitive comprehension of the energy functions (modeling intermolecular interactions) involved. In this paper, we propose visualizations designed to enable the characterization of interaction forces by taking into account several relevant variables such as molecule-ligand distance and the energy function, which is essential to understand binding affinities. We put emphasis on mapping molecular docking paths obtained from Molecular Dynamics or Monte Carlo simulations, and provide time-dependent visualizations for different energy components and particle resolutions: atoms, groups or residues. The presented visualizations have the potential to support domain experts in a more efficient drug or enzyme design process.

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“…Atomic structure visualization. Many authors focused on massive atomic model rendering [24,39], such as LOD approaches [11,30,37], instancing [12], or billboards and glyphs [13,17,45,40]. Grottel et al described an approach which exploits two-level coherent culling to render large-scale molecular dynamics results [18].…”

Section: Related Workmentioning

confidence: 99%

“…Falk et al illustrate the different transport modes in mitogen-activated protein kinase signaling molecules (MAPK) within a cell [12]. Molecular trajectories and reactions are identified by augmenting geometric objects, such as paths that illustrate molecule trajectories, and arrows that depict reactions.…”

Section: Related Workmentioning

confidence: 99%

Real-Time Molecular Visualization Supporting Diffuse Interreflections and Ambient Occlusion

Skånberg

Vázquez

Guallar

et al. 2016

IEEE Trans. Visual. Comput. Graphics

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(a) Time step 1 (b) Time step 2 (c) Time step 3 Fig. 1. By deriving analytic expressions, we can enhance molecular visualizations and realize interreflections in real-time. The images (a-c) show three time steps of a molecular simulation investigating the interaction between a magenta-colored ligand and a receptor molecule, which receives exaggerated diffuse interreflections. Due to these interreflections it can be seen how the ligand enters the active site.Abstract-Today molecular simulations produce complex data sets capturing the interactions of molecules in detail. Due to the complexity of this time-varying data, advanced visualization techniques are required to support its visual analysis. Current molecular visualization techniques utilize ambient occlusion as a global illumination approximation to improve spatial comprehension. Besides these shadow-like effects, interreflections are also known to improve the spatial comprehension of complex geometric structures. Unfortunately, the inherent computational complexity of interreflections would forbid interactive exploration, which is mandatory in many scenarios dealing with static and time-varying data. In this paper, we introduce a novel analytic approach for capturing interreflections of molecular structures in real-time. By exploiting the knowledge of the underlying space filling representations, we are able to reduce the required parameters and can thus apply symbolic regression to obtain an analytic expression for interreflections. We show how to obtain the data required for the symbolic regression analysis, and how to exploit our analytic solution to enhance interactive molecular visualizations.

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Visualization of signal transduction processes in the crowded environment of the cell

Cited by 22 publications

References 14 publications

Agent-based simulation of reactions in the crowded and structured intracellular environment: Influence of mobility and location of the reactants

Agent-based simulation of reactions in the crowded and structured intracellular environment: Influence of mobility and location of the reactants

Physics-Based Visual Characterization of Molecular Interaction Forces

Real-Time Molecular Visualization Supporting Diffuse Interreflections and Ambient Occlusion

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