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10:00am

Science: Membrane protein
    Tuesday July 17, 2012 10:00am - 10:30am @ King Arthur 3rd Floor

    Science: Membrane protein simulations under asymmetric ionic concentrations

    Abstract: Important cellular processes, such as cell-cell recognition, signal transduction, and transport of electrical signals are controlled by membrane proteins. Membrane proteins act as gatekeepers of the cellular environment by allowing passage of ions, small molecules, or nascent proteins under specific environmental signals such as transmembrane voltage, changes in ionic concentration, or binding of a ligand. Molecular dynamics simulations of membrane proteins, performed in a lipid bilayer environment, mimic the cellular environment by representing the solvent, lipids, and the protein in full atomistic detail. These simulations employ periodic boundary conditions in three dimensions to avoid artifacts associated with the finite size of the system. Under these conditions, the membrane protein system is surrounded by ionic solutions on either side of the membrane whose properties cannot be changed independently. We have developed a computational method that allows simulations of membrane proteins under periodic boundary condition while controlling the two ionic solutions properties independently. In this method, an energy barrier is introduced between the two adjacent unit cells and separates the two ionic solutions. The height of the barrier affects the chemical potential of the ions on each side of the barrier, and thus allows for individual control over ionic properties. During the course of the simulation, the height of the barrier is adjusted dynamically to reach the proper ionic concentration on each side. This method has been implemented in the Tcl interface of the molecular dynamics program NAMD. 

     

    We have applied this method to simulate the voltage-gated potassium channel Kv1.2 under physiological conditions, in which the extracellular solution is made of 10mM KCl and 100mM of NaCl solution, while the intracellular solution has an ionic concentration of 100mM KCl and 10mM NaCl. The simulations maintain a 1:10 and 10:1 ratio between ionic concentrations on each side. The simulations are performed under a voltage bias of 100mV and provide the first simulation of potassium channels under the exact physiological condition. 

     The method has also been applied to simulate ionic currents passing through OmpF, an outer membrane porin, under membrane potentials. Here we were able to accurately calculate the reversal potential of the OmpF channel in a tenfold salt gradient of 0.1 intracellular to 1M extracellular KCl. Our results agree with experimental ion conductance measurements and reproduce key features of ion permeation and selectivity of the OmpF channel. Specifically, the I-V plots obtained under asymmetric ionic solutions revealed the natural asymmetry in the channel caused by increased conductance rates observed at positive potentials, as well as the inherent cation-selectivity of the OmpF pore. Therefore, we have developed a method that directly relates molecular dynamics simulations of ionic currents to electrophysiological measurements in ion channels.

     



    Speakers

    Type Science Track
    Session Titles Biological Applications


10:30am

Science: Exploiting HPC
    Tuesday July 17, 2012 10:30am - 11:00am @ King Arthur 3rd Floor

    Science: Exploiting HPC Resources for the 3D-Time Series Analysis of Caries Lesion Activity.

    Abstract: We present a research framework to analyze 3D-time series caries lesion activity based on collections of SkyScanμ-CT images taken at different times during the dynamiccaries process. Analyzing caries progression (or reversal)is data-driven and computationally demanding. It involvessegmenting high-resolution μ-CT images, constructing 3Dmodels suitable for interactive visualization, and analyzing3D and 4D (3D + time) dental images. Our development exploitsXSEDE’s supercomputing, storage, and visualizationresources to facilitate the knowledge discovery process. Inthis paper, we describe the required image processing algorithmsand then discuss the parallelization of these methodsto utilize XSEDE’s high performance computing resources.We then present a workflow for visualization and analysis usingParaView. This workflow enables quantitative analysisas well as three-dimensional comparison of multiple temporaldatasets from the longitudinal dental research studies.Such quantitative assessment and visualization can help usto understand and evaluate the underlying processes thatarise from dental treatment, and therefore can have significantimpact in the clinical decision-making process andcaries diagnosis.



    Speakers

    Type Science Track
    Session Titles Biological Applications


11:00am

Science: Transforming molecular biology
    Tuesday July 17, 2012 11:00am - 11:30am @ King Arthur 3rd Floor

    Science: Transforming molecular biology research through extreme accleration of AMBER molecular dynamics simulations: Sampling for the 99%. 

    Abstract: This talk will cover recent developments in the acceleration of Molecular Dynamics Simulations using NVIDIA Graphics Processing units with the AMBER software package. In particular it will focus on recent algorithmic improvements aimed at accelerating the rate at which phase space is sampled. A recent success has been the reproduction and extension of key results from the DE Shaw 1 millisecond Anton MD simulation of BPTI (Science, Vol. 330 no. 6002 pp. 341-346) with just 2.5 days of dihedral boosted AMD sampling on a single GPU workstation, (Pierce L, Walker R.C. et al. JCTC, 2012 in review). These results show that with careful algorithm design it is possible to obtain sampling of rare biologically relevant events that occur on the millisecond timescale using just a single $500 GTX580 Graphics Card and a desktop workstation. Additional developments highlighted will include the acceleration of AMBER MD simulations using graphics processing units including Amazon EC2 and Microsoft Azure Cloud based automated ensemble calculations, a new precision model optimized for the upcoming Kepler architecture (Walker R.C. et al, JCP, 2012, in prep) as well as approaches for running large scale multi-dimensional GPU accelerated replica exchange calculations on Keeneland and BlueWaters.

     



    Speakers

    Type Science Track
    Session Titles Biological Applications


11:30am

Science: Invited Talk: Multiscale
    Tuesday July 17, 2012 11:30am - 12:00pm @ King Arthur 3rd Floor

    Science: Invited Talk:  Multiscale simulations of blood-flow: from a platelet to an artery

    Abstract: We review our recent advances on multiscale modeling of blood flow including blood rheology. We focus on the objectives, methods, computational complexity and overall methodology for simulations at the level of glycocalyx (<1 micron), blood cells (2-8 microns) and up to larger arteries ($O(cm)$). The main findings of our research and future directions are summarized. We discuss the role of High Performance Computers for multiscale modeling and present new parallel visualization tools. We also present results of simulations performed with our coupled continuum-atomistic solver on up to 300K cores, modeling initial stages of blood clot formation in a brain aneurysm. 



    Speakers

    Type Science Track
    Session Titles Biological Applications


 

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