Bulletin of the American Physical Society
2006 73rd Annual Meeting of the Southeastern Section of the APS
Thursday–Saturday, November 9–11, 2006; Williamsburg, Virginia
Session GB: Biophysics |
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Chair: Richard Superfine, University of North Carolina, Chapel Hill Room: Williamsburg Hospitality House Jamestown |
Friday, November 10, 2006 8:00AM - 8:12AM |
GB.00001: Electrostatic effects on the folding stability of FKBP Jyotica Batra, Huan-Xiang Zhou Charged residues play important roles in the folding of proteins and their interactions with biological targets. We have developed computational models for predicting electrostatic contributions to protein folding and binding stability. To rigorously test and further refine these models, we carried out experimental studies on the effects of charge mutations on the folding stability of FKBP. Two close homologues of FKBP, FKBP12 and FKBP12.6, differ in 18 of 107 positions, and 8 of which involve substitutions of charged residues. These 8 substitutions were introduced on FKBP12 and their effects on the folding stability were measured. The changes in unfolding free energy varied from -0.34 to 0.65 kcal/mol. A double and a triple mutation were introduced to accumulate the stabilization effect of individual substitutions, resulting an increase in stability of about 0.84 kcal/mol. On the other hand, neutralizing one or both partners of a conserved salt bridge reduced the stability by as much as 0.64 kcal/mol. These results suggest that charged residues can modulate the folding stability significantly. To further exploit stabilization effects of charged residues, experiments are now underway to introduce charge mutations that are modeled after a thermophilic FKBP. [Preview Abstract] |
Friday, November 10, 2006 8:12AM - 8:24AM |
GB.00002: Energy Landscape and Transition State of Protein-Protein Association Ramzi Alsallaq, Huan-Xiang Zhou Formation of a stereospecific protein complex is favored by specific interactions between two proteins but disfavored by the loss of translational and rotational freedom. Echoing the protein folding process, we have previously proposed a transition state for protein-protein association. Here we clarify the specification of the transition state by working with two toy models for protein association. The models demonstrate that a sharp transition between the bound state with numerous short-range interactions but restricted translation and rotational freedom and the unbound state with at most a small number of interactions but expanded configurational freedom. This transition sets the outer boundary of the bound state as well as the transition state for association. The energy landscape is funnel-like, with the deep well of the bound state surrounded by a broad shallow basin. This formalism of protein-protein association is applied to four protein-protein complexes, and is found to give accurate predictions for the effects of charge mutations and ionic strength on the association rates. [Preview Abstract] |
Friday, November 10, 2006 8:24AM - 8:36AM |
GB.00003: Kinetics of Vascular Remodeling: Comparison of Solver Approaches R.C. Ward, J.J. Nutaro, K.L. Kruse, E.C. O'Quinn, A.R. Reedy-Jackson, M.M. Woerner Results will be presented for kinetics of matrix metalloproteinases (MMP), enzymes that play a significant role in vascular remodeling. Three different computational approaches for well-mixed kinetics processes will be analyzed and compared. The kinetics of one MMP, namely MMP2, were elucidated using a model and rate constants from published literature$^{1}$ and implemented using the \textit{JSim }environment (see nsr.bioeng.washington.edu).$^{ }$Further investigations of this pathway were undertaken using System Biology Workbench (SBW) (see sbw.kgi.edu), where the system of kinetic equations was created using an interactive visual interface. Using SBW the complexity of the kinetics was evaluated using phase space analysis. Finally, we implemented the kinetics model using Discrete Event System Specification (DEVS). Using \textit{adev }(see www.ece.arizona.edu/$\sim $nutaro), an open-source DEVS modeling environment we demonstrate that continuous, well-mixed, enzyme kinetics can be modeled using discrete event simulation. The three computational environments will be compared and their utility and comprehensiveness evaluated. 1. Karagiannis, E. D. and Popel, A. S., J. of Biological Chemistry, \textbf{279} (37):39105--39114, 2004. [Preview Abstract] |
Friday, November 10, 2006 8:36AM - 8:48AM |
GB.00004: Dynamic model of active transport: application to sodium/potassium pump Brian Keating, Robert Finkel Active transport is a process where some energetic agent, generally an enzyme powered by ATP, conveys ions across a membrane. Here we present a novel physical approach to modeling the dynamics of active transport. Specifically, we employ a general method whereby the non-equilibrium energetics of active transport derive simply from the chemical kinetic rate equations. The case treated here is an exchange of sodium and potassium ions across a cell membrane at the expenditure of one ATP---a process common to most life forms. The generic rate equations are readily formulated and only two well-established quantities are input, the ATP energy value and the membrane potential. The model uses this sparse information to generate several agreements with experimental values including the relative concentrations of Na and K on either side of the membrane and the celebrated 3:2 transfer ratio of sodium to potassium. [Preview Abstract] |
Friday, November 10, 2006 8:48AM - 9:00AM |
GB.00005: Cellular Potts Models of Fruit Fly Embryogenesis Jason Rohner, Shane Hutson Biologists have extensively studied embryonic development in the fruit fly (\textit{Drosophila melangaster}) as a model for morphogenesis. Our overall goal is to understand how the cellular rearrangements of morphogenesis are caused by the underlying forces between cells. To that end, we are developing means to replicate fruit fly embryogenesis (from cellular differentiation to dorsal closure) using cellular Potts models. Cells are described as collections of like ``spins''; and spin-spin interaction energies are used to describe the forces along cell boundaries. Using a four state (spin-type) model (three tissue types and the surrounding media) we have reproduced cell sorting as well as engulfment of a surface grouping of tissue. Cell sorting can be accomplished using only the spin-spin interaction energies with the volume components being used only for cell size management. We are currently attempting to replicate the experimentally determined geometry and dynamics of dorsal closure. This modeling will take advantage of software tools developed at Notre Dame for looking at cellular Potts models and packaged as CompuCell3D. [Preview Abstract] |
Friday, November 10, 2006 9:00AM - 9:12AM |
GB.00006: GBr$^{6}$: a Parameterization-Free, Accurate, Analytical Generalized Born Model Harianto Tjong, Huan-Xiang Zhou The Poisson-Boltzmann (PB) equation is widely used for modeling electrostatic effects for macromolecules. Generalized Born (GB) models have been developed to mimic PB results at substantial lower computational cost. Here we report an analytical GB model that reproduces PB results with high accuracy. The analytical approach is adapted from Gallicchio and Levy (J. Comput. Chem 25:479, 2004), but we implement an improvement of the Coulomb-field approximation proposed by Grycuk (J. Chem. Phys. 119:9, 2003). Benchmarked against PB results, our GB model has an average error of only 0.5{\%} for a representative set of 55 proteins and of 0.4{\%} and 0.2{\%}, respectively, for folded and unfolded conformations of cytochrome $b_{562}$ sampled in molecular dynamics simulations. The dependencies of the electrostatic solvation free energy on solute and solvent dielectric constants and on salt concentration are fully accounted for in this model. [Preview Abstract] |
Friday, November 10, 2006 9:12AM - 9:24AM |
GB.00007: Fabrication of Magnetically Actuated Polymeric Nanorod Arrays to Mimic Biological Cilia A.R. Shields, B.A. Evans, R.L. Carroll, R. Superfine We report on successful fabrication of free-standing polymer nanorod arrays capable of actuation via externally applied magnetic fields. Our primary motivation is to mimic the ability of epithelial lung cilia to promote microscale fluid transport. Additionally, nanoscale actuator arrays of this nature have a wide variety of possible applications including microfluidics, sensing, and photonics. To fabricate these structures we utilize porous polycarbonate track-etched membranes as templates for a dispersion of a magnetic nanoparticle ferrofluid in polydimethylsiloxane (PDMS). Crosslinking of the polymer followed by subsequent dissolution of the membrane releases the rod array. With this method we have successfully fabricated rods with diameters down to 200 nanometers and lengths of 10-25 microns. Rods of various sizes have been successfully actuated with permanent magnets as well as an integrated magnetic force microscope that was developed in-house. We have demonstrated that actuation induces local fluid flow and are currently developing increased control over the array's actuation pattern to more closely resemble that of biological cilia. [Preview Abstract] |
Friday, November 10, 2006 9:24AM - 9:36AM |
GB.00008: Spot Surface Labeling of Magnetic Microbeads and Application in Biological Force Measurements Ashley Estes, E. Tim O'brien, David Hill, Richard Superfine Biological force measurements on single molecules and macromolecular structures often use microbeads for the application of force. These techniques are often complicated by multiple attachments and nonspecific binding. In one set of experiments, we are applying a magnetic force microscope that allows us to pull on magnetic beads attached to ciliated human bronchial epithelial cells. These experiments provide a means to measure the stall force of cilia and understand how cilia propel fluids. However, because we are using beads with diameters of one and 2.8 microns, and the diameter of human airway cilia is approximately 200 nm, we cannot be assured that the bead is bound to a single cilium. To address this, we have developed a sputter coating technique to block the biotin binding capability of the streptavidin labeled bead over its entire surface except for a small spot. These beads may also have applications in other biological experiments such as DNA force experiments in which binding of a single target to an individual bead is critical. [Preview Abstract] |
Friday, November 10, 2006 9:36AM - 9:48AM |
GB.00009: Positron Emission Imaging Studies of Carbon Partitioning in Plants M.R. Kiser, C.R. Howell, A.S. Crowell, C.D. Reid, R.P. Phillips Over the past two centuries the atmospheric CO$_2$ concentration has increased dramatically, and climate experts predict that CO$_2$ levels will double by the end of this century. To understand plant responses to these global change conditions, we use short-lived radioisotope labeling techniques to trace the distribution of carbon in plants grown at ambient (350 PPM) and elevated (700 PPM) CO$_2$ concentrations. The plants are grown and labeled in environmental growth chambers at the Duke University Phytotron, and carbon-11 dioxide is produced at TUNL using the $^{14}$N(p,$\alpha$)$^{11}$C reaction. The close proximity of TUNL and the Duke University Phytotron creates a unique opportunity for these global change studies. Recent experiments seek to quantify the fraction of carbon that is released from the roots either as soluble carbon in the root nutrient solution or as respired CO$_2$ dissolved in the nutrient solution. Preliminary results from this experiment will be presented, as well as results from single detectors collimated to restrict the field of each detector to a specific region of the plant and development of a high spatial resolution planar positron emission imager. [Preview Abstract] |
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