28,988 research outputs found
A flexible architecture for modeling and simulation of diffusional association
Up to now, it is not possible to obtain analytical solutions for complex
molecular association processes (e.g. Molecule recognition in Signaling or
catalysis). Instead Brownian Dynamics (BD) simulations are commonly used to
estimate the rate of diffusional association, e.g. to be later used in
mesoscopic simulations. Meanwhile a portfolio of diffusional association (DA)
methods have been developed that exploit BD.
However, DA methods do not clearly distinguish between modeling, simulation,
and experiment settings. This hampers to classify and compare the existing
methods with respect to, for instance model assumptions, simulation
approximations or specific optimization strategies for steering the computation
of trajectories.
To address this deficiency we propose FADA (Flexible Architecture for
Diffusional Association) - an architecture that allows the flexible definition
of the experiment comprising a formal description of the model in SpacePi,
different simulators, as well as validation and analysis methods. Based on the
NAM (Northrup-Allison-McCammon) method, which forms the basis of many existing
DA methods, we illustrate the structure and functioning of FADA. A discussion
of future validation experiments illuminates how the FADA can be exploited in
order to estimate reaction rates and how validation techniques may be applied
to validate additional features of the model
Simulated single molecule microscopy with SMeagol
SMeagol is a software tool to simulate highly realistic microscopy data based
on spatial systems biology models, in order to facilitate development,
validation, and optimization of advanced analysis methods for live cell single
molecule microscopy data. Availability and Implementation: SMeagol runs on
Matlab R2014 and later, and uses compiled binaries in C for reaction-diffusion
simulations. Documentation, source code, and binaries for recent versions of
Mac OS, Windows, and Ubuntu Linux can be downloaded from
http://smeagol.sourceforge.net.Comment: v2: 14 pages including supplementary text. Pre-copyedited,
author-produced version of an application note published in Bioinformatics
following peer review. The version of record, and additional supplementary
material is available online at:
https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btw10
Anomalous relaxation kinetics of biological lattice-ligand binding models
We discuss theoretical models for the cooperative binding dynamics of ligands
to substrates, such as dimeric motor proteins to microtubules or more extended
macromolecules like tropomyosin to actin filaments. We study the effects of
steric constraints, size of ligands, binding rates and interaction between
neighboring proteins on the binding dynamics and binding stoichiometry.
Starting from an empty lattice the binding dynamics goes, quite generally,
through several stages. The first stage represents fast initial binding closely
resembling the physics of random sequential adsorption processes. Typically
this initial process leaves the system in a metastable locked state with many
small gaps between blocks of bound molecules. In a second stage the gaps
annihilate slowly as the ligands detach and reattach. This results in an
algebraic decay of the gap concentration and interesting scaling behavior. Upon
identifying the gaps with particles we show that the dynamics in this regime
can be explained by mapping it onto various reaction-diffusion models. The
final approach to equilibrium shows some interesting dynamic scaling
properties. We also discuss the effect of cooperativity on the equilibrium
stoichiometry, and their consequences for the interpretation of biochemical and
image reconstruction results.Comment: REVTeX, 20 pages, 17 figures; review, to appear in Chemical Physics;
v2: minor correction
Anomalous relaxation kinetics of biological lattice-ligand binding models
We discuss theoretical models for the cooperative binding dynamics of ligands
to substrates, such as dimeric motor proteins to microtubules or more extended
macromolecules like tropomyosin to actin filaments. We study the effects of
steric constraints, size of ligands, binding rates and interaction between
neighboring proteins on the binding dynamics and binding stoichiometry.
Starting from an empty lattice the binding dynamics goes, quite generally,
through several stages. The first stage represents fast initial binding closely
resembling the physics of random sequential adsorption processes. Typically
this initial process leaves the system in a metastable locked state with many
small gaps between blocks of bound molecules. In a second stage the gaps
annihilate slowly as the ligands detach and reattach. This results in an
algebraic decay of the gap concentration and interesting scaling behavior. Upon
identifying the gaps with particles we show that the dynamics in this regime
can be explained by mapping it onto various reaction-diffusion models. The
final approach to equilibrium shows some interesting dynamic scaling
properties. We also discuss the effect of cooperativity on the equilibrium
stoichiometry, and their consequences for the interpretation of biochemical and
image reconstruction results.Comment: REVTeX, 20 pages, 17 figures; review, to appear in Chemical Physics;
v2: minor correction
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