We used Virtual Cell to develop a quantitative 3D model of PIP2
signaling in Cerebellar Purkinje spines. Specifically, we modeled the
hydrolysis of PIP2 resulting in IP3 production, and focused our efforts
on exploring sources of abundant PIP2 supply. We also virtually
photobleached PIP2 in patches of dendrite and in spines, to analyze
lateral diffusion of PIP2 in the spiny dendrite membrane. In addition
to our 3D spatial model, we created a 1D model that gives similar
results to simulations run in our constructed and our experimentally
derived 3D geometries. We obtained time-dependent boundary conditions
for IP3 from the 1D models, based on the length of each respective 3D
geometry, and used those boundary conditions in our 3D models. We also
used IP3 output from spatial simulations in our constructed 3D geometry
as input for a 0D compartmental model previously published by our group
in order to investigate the behavior of calcium transients dependent on
the IP3 signal. The compartmental model considers molecules, reactions,
and fluxes occurring in separate compartments with specific
surface/volume ratios. It runs faster than the 1D and 3D models,
because it does not explicitly treat diffusion. Simulation results
indicate that both stimulated PIP2 synthesis (consistent with a similar
mechanism established in earlier work for neuroblastoma cells) and
local PIP2 sequestration produce large amplitudes of IP3 and
significant calcium transients. (Supported by NIH Grant RR013186)
Demo will provide details of the model behind the platform presentation
(1841-Plat), "Analysis of PIP2 Signaling in Cerebellar Purkinje
Spines", which will occur on Tuesday at 4pm, in Platform AR: Calcium
Signaling. Visitors to the booth may:
The Structure-Function Linkage Database (SFLD) provides highly curated
information about the relationships between protein sequence, structure
and function. The SFLD currently focuses on enzymes, using a
superfamily-centric organization designed to allow users to easily
investigate how conserved folds and active sites are able to perform a
wide variety of chemical reactions. The information within the SFLD
includes sequences, structures, enzyme reactions (including partial
reactions), the specific residues of each enzyme that participate in
the reaction (and their role when known), hidden Markov models based on
family and superfamily classifications, and literature references. In
an effort to make assignments of function, superfamily, etc.
transparent, assignment evidence codes and extensive metadata are
easily accessible. Users can search the database using a sequence
(useful in determining the function of a newly sequenced enzyme), a
full or partial reaction (useful in identifying a template for enzyme
engineering), or through a variety of keyword searches. We are in the
process of integrating the SFLD with the network analysis program
Cytoscape, to allow users to visualize overall sequence relationships
in diverse superfamilies as well as to place a sequence of interest in
the context of its superfamily, thus facilitating functional
classification. The SFLD is freely available via a web interface at
http://sfld.rbvi.ucsf.edu.
I'll demonstrate some new capabilities of the UCSF Chimera visualization
program (
www.cgl.ucsf.edu/chimera)
including tracing surfaces of intracellular
membranes or virus layers in electron microscopy density maps, extracting
density within surfaces, slicing tomography data at arbitrary angles to show
nuclear pores, and displaying data cross-sections as topographic relief
surfaces.
UCSF Chimera is an interactive molecular graphics program for analysis
of proteins, nucleic acids, volumetric and sequence data. and for
creating publication images. The density map display and analysis
capabilities are being developed for studying single particle
reconstructions and EM tomography. Chimera runs on Windows, Mac, and
Linux operating systems, is free for academic use, and is developed by
the Resource for Biocomputing, Visualization and Informatics.
Introducing quantitative cell biology and modeling into undergraduate
and graduate biology courses faces a key challenge of access to
appropriate teaching materials. In this demo, visitors to the booth
will be introduced to:
- publicly accessible models in the Virtual Cell that can be used to teach simple and complex biological behaviors
- classroom assignments and exercises that make use of models and modeling to teach modeling cell biology
- a prototype format and TWiki for the development of modules in Quantitative Cell Biology.
Quantitative Cell Biology involves moving from existing knowledge and
experimental data to a proposed model that embodies hypotheses in
mathematical form. The models are used to run simulations from which
new experiments maybe designed and results predicted. The Virtual Cell,
developed by the NIH designated National Resource for Cell Analysis and
Modeling (NRCAM), is designed for biologists to develop models and
simulations of cellular processes. It can be used to teach students to
model and the significance of quantitative experiments. The models,
research projects, and exercises presented have been used in
undergraduate and graduate courses to teach students how to construct
models, understand biological systems, and analyze complex experimental
data such as FRAP experiments. Examples of publicly accessible
biological models in Virtual Cell include nuclear transport, calcium
dynamics, and signal transduction. Accessible models are one part of a
framework for computational cell biology teaching modules proposed by
attendees of the Kavli Institute for Theoretical Physics course on
Biological Switches and Clocks. These modules are meant to facilitate
the introduction of quantitative cell biology to undergraduate biology
courses. An initial TWiki has been created to foster development of the
computational cell biology teaching modules. Teaching modules will make
use of the Virtual Cell and other simulation tools. (Supported by NIH
grants P41-RR13186, U54-RR022232, and by NSF grants PACI 6245-7 and
PHY05-51164)
The National Center of Macromolecular Imaging (http://ncmi.bcm.edu) is
dedicated to push the resolution of single particle cryo-EM towards
atomic resolution via innovative use of modern electron cryomicroscopes
and development of new algorithms for automated data collection,
electronic notebook, data processing and structure analysis. All of our
technology developments are driven by biological applications initiated
by our Center collaborators.
The most notable and recent achievements are the successful tracing of
the Cα backbone of the GroEL (in collaboration with Dr. David
Chuang at UT Southwestern Medical School) and of the epsilon15
bacteriophage (in collaboration with Wen Jiang at Purdue University and
Jonathan King at MIT). The models of these proteins are built from the
cryoEM density maps without reference to any crystal structures. These
cryo-EM structures also reveal novel biological insights previously not
seen at low resolution cryo-EM maps.
Title:
Gfit Demo: Universal Approach to global fitting of data from multiple types of experiments to computational models.
Presenter:Mikhail Levin
Abstract:
In this demonstration I will show how to globally fit multiple
experiments into a computational model. Global fitting allows us to
verify that the model is consistent with all experimental observations
and to estimate the parameters of the model. To simplify global
fitting of many experiments of different types we have developed gfit,
an open source program (
http://gfit.sf.net).
Computational models used by gfit may implement any algorithm for
simulating experiments performed with the system. By reading the
interface description, gfit discovers how to execute the model and how
to interpret the experimental data. The interface description language
is simple, but flexible enough to accommodate complex experiments as
well as rule-based models. Our approach has been used for creating
models and for global analysis of data from many different sources
including rapid stopped-flow and quench-flow, fluorescence correlation
spectroscopy, and surface plasmon resonance. Visitors will be shown
how gfit interacts with models, how to create a model, and how to
analyze multiple experiments taking into account different experimental
conditions. More information about this approach can be found in
poster 2463.06-Pos/B577.06
Title:Using Virtual Cell to generate and explore quantitative model of actin polymerization at the leading edge of cells.
Presenter:Les Loew
Abstract:
This Demo will
provide details of the model behind poster 3165-Pos/B468, "A
Quantitative Model of Actin Polymerization at the Cell Leading Edge",
which will be displayed on Wednesday. It will offer an opportunity for
visitors to the booth to:
- Learn about the components of the
model in detail.
- Interact with the model by changing
parameters or mechanisms.
- Gain an introduction to the Virtual
Cell modeling and simulation environment.
The original
abstract of the poster provides a summary of the model and simulation
results: Branching of actin filaments through the action of the Arp2/3
complex nucleates new polymerization in the lamellipodium of cells.
This active polymer growth pushes the branched network of filaments
rearward and contributes to the protrusive force that propels the
cell's leading edge forward. In this work, we have constructed a
quantitative 3D spatial model based on the mechanisms of actin
polymerization using the Virtual Cell software. The model explicitly
incorporates the following mechanisms: inter-conversions between the
ATP, ADP and ADP-Pi forms of both monomeric G-actin and filamentous
F-actin; assembly and disassembly of these 3 nucleotide-bound monomer
forms to each of the 3 forms of barbed and pointed ends; acceleration
of nucleotide exchange on G-actin by profilin; profilin-mediated
delivery of G-actin to barbed ends; capping of the 3 forms of barbed
ends; annealing and fragmentation of actin filaments; buffering of
G-actin by thymosin-Β4; severing and accelerated disassembly of
actin filaments by cofilin; branching and nucleation of actin filaments
by activated Arp2/3; activation of Arp2/3 at the cell membrane and
dissociation of Arp2/3 branches in the cytoplasm. The model
recapitulates many observations including the high spatial gradient of
F-actin between the cell leading edge and the interior. In particular,
speckle microscopy data has revealed that while actin filament assembly
is highly concentrated at the leading edge of cells, a sharp transition
to strong actin filament disassembly occurs just 1µm away;
further into the cell interior, assembly and disassembly are
approximately balanced. The model shows that this arises from the
interplay of retrograde F-actin flow and branch dissociation, which
exposes a high concentration of disassembling pointed ends that peaks
2µm away from the activated edge. (supported by NIH grants
U54RR022232, P41RR13186 and U54GM64346)
Title:New Features in UCSF Chimera
Presenter:Elaine Meng, Eric Pettersen
Abstract:
UCSF Chimera is an
interactive molecular graphics program with a wide variety of
features. Applications include structure analysis (hydrogen bonding,
contacts, clashes), structure superposition and comparison, ensemble
analysis (trajectory playback, ensemble clustering), analysis in the
context of other types of data (sequence alignments, density maps), and
making high-quality images and movies.
Recently added
features include display and incorporation of amino acid sidechain
rotamers from backbone-dependent and -independent libraries, creation
of "morph trajectories" between different conformations of a protein or
even different proteins, and generating shadowed images with POV-Ray,
which is embedded in Chimera. We will demonstrate these features as
well as other features (whether new or not) upon request.
Chimera is available for Windows, Mac, Linux and other platforms and
can be downloaded free of charge for noncommercial use (www.cgl.ucsf.edu/chimera).
Title:
The Virtual Cell: Tutorial on new capabilities
Presenter:Ion I. Moraru
Abstract:
The Virtual Cell (VCell—
http://www.vcell.org/)
has been developed from the beginning with the vision of providing an
easy access for cell biologists to sophisticated and powerful
computational tools. It has been developed and deployed as a
web-based, distributed, client-server system. VCell provides a
separation of layers representing biological models, physical
mechanisms, geometry, mathematical models and numerical methods. This
separation clarifies the impact of modeling decisions, assumptions, and
approximations. The result is a physically consistent, mathematically
rigorous, spatial modeling and simulation framework for cell biology.
VCell can formulate and solve reaction-diffusion-advection-electrophysiological
problems in arbitrary
geometries (as well as in compartmental approximations using ODE-only
simulations), using either deterministic or stochastic algorithms.
Users create biological models and VCell will automatically generate an
appropriate mathematical encoding for running a simulation, and also
automatically generate and compile the appropriate computer code.
Using the VCell database, models and model components can be reused and
updated, as well as privately shared among collaborating groups, or
published. To date, more than 1,500 independent users worldwide have
created and run simulations with VCell.
VCell has been continuously
and rapidly growing in capabilities and complexity over the past
several years. The presentation sessions will include: (i) a short
talk presenting the concepts and abstractions underlying the design of
the VCell platform, and (ii) demonstrations of a typical workflows of
building models, creating applications, running simulations, viewing
and exporting results, with special emphasis on recently introduced
capabilities: stochastic simulations, membrane diffusion, parameter
scans and optimization, field data, and rule-based modeling via
BioNetGen integration. We will also introduce upcoming developments,
such as: a new, open-source, extensible architecture, grid computing
via OpenScienceGrid, and the Virtual Experiment framework.
Participants can try out the VCell client and interactively discuss
features and technical details.
Title:
Introduction to the UCSF Chimera molecular modeling package
Presenter: Scooter Morris
Abstract:
UCSF Chimera is a program for interactive molecular graphics and
modeling. It provides standard graphics features as well as more
unique, domain-specific tools; the menu and command-line interfaces
provide a rich and overlapping set of functionality. The Introduction
to Chimera shows frequently used coloring and display options,
including molecular representations such as ribbons, "pipes and
planks," surfaces, and abstract renderings of nucleotides. Other
general features shown are distance measurements, bond angle rotations,
H-bond identification, and display of the corresponding amino acid
and/or nucleotide sequences. Attributes such as B-factors and
hydrophobicities can be rendered visually with colors, atomic radii,
and "worm" thickness. Chimera includes detailed user documentation and
is available for Windows, Linux, Mac OS X (with X11), IRIX, and Tru64
Unix. Chimera is free for academic, government, and non-profit use and
can be downloaded from
http://www.cgl.ucsf.edu/chimera.
Title:
structureViz: Linking Cytoscape to Chimera
Presenter: Scooter Morris
Abstract:
UCSF
structureViz is a Cytoscape plugin that links the visualization of
biological networks (and biological relationships expressed as
networks) provided by Cytoscape with the visualization and analysis of
macromolecular structures and sequences provided by UCSF Chimera.
structureViz provides commands to open structures in Chimera,
manipulate those structures, and
align open structures using Chimera's Sequence/Structure tools.
n order to load a structure associated with a node, the
Protein Databank (PDB) identifier (or identifiers if there are more
than one) must be present as an attribute of that node. Currently,
structureViz will look for an attribute named Structure, pdb, or
pdbFileName. When a structure is opened, structureViz provides an
alternative interface to Chimera: the Cytoscape Molecular Structure
Navigator. This interface uses a tree-based paradigm to allow users to
select and effect the display of models, chains, and residues, mostly
through the use of context menus. Additional commands allow for
selection by chemistry (Ligand, Ions, Solvent, Secondary Structure, and
in the model context menu, Functional Residues). Users can also take
advantage of Chimera's structural alignment capabilities by using the
"Align" command.
structureViz is available for download
at
http://www.rbvi.ucsf.edu/Research/cytoscape/structureViz/.
Title:
Exploring Biomolecular Machines with NAMD and VMD
Presenter:Yi Wang
Abstract:
The Theoretical and Computational Biophysics Group, located at the
Beckman Institute of the University of Illinois at Urbana-Champaign,
operates the NIH Resource for Macromolecular Modeling and
Bioinformatics. The Resource brings advanced molecular modeling,
bioinformatics, and computational technologies to bear on questions of
biomedical relevance through direct collaboration with experimental
researchers, the distribution of user-friendly cutting-edge software,
and a broad range of training and dissemination activities.
The flagship software packages NAMD and VMD, both distributed free of
charge with source code, facilitate the discovery process from
analysis, through modeling, to visualization of the molecular apparatus
in biological cells:
-
NAMD, recipient of a 2002 Gordon Bell Award, is a parallel molecular dynamics code used regularly to simulate systems of 1,000,000 atoms and beyond on both large supercomputers and inexpensive Linux clusters.
-
VMD is a molecular visualization program for displaying, animating, and analyzing large biomolecular systems using hardware-accelerated 3-D graphics and built-in scripting.
