Bulletin of the American Physical Society
APS March Meeting 2010
Volume 55, Number 2
Monday–Friday, March 15–19, 2010; Portland, Oregon
Session Y10: Computational Molecular Biophysics |
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Sponsoring Units: DBP Chair: Gregory Grason, University of Massachusetts Room: A106 |
Friday, March 19, 2010 8:00AM - 8:12AM |
Y10.00001: Frustration in protein elastic network models Timothy Lezon, Ivet Bahar Elastic network models (ENMs) are widely used for studying the equilibrium dynamics of proteins. The most common approach in ENM analysis is to adopt a uniform force constant or a non-specific distance dependent function to represent the force constant strength. Here we discuss the influence of sequence and structure in determining the effective force constants between residues in ENMs. Using a novel method based on entropy maximization, we optimize the force constants such that they exactly reporduce a subset of experimentally determined pair covariances for a set of proteins. We analyze the optimized force constants in terms of amino acid types, distances, contact order and secondary structure, and we demonstrate that including frustrated interactions in the ENM is essential for accurately reproducing the global modes in the middle of the frequency spectrum. [Preview Abstract] |
Friday, March 19, 2010 8:12AM - 8:24AM |
Y10.00002: Periplasmic Vestibule Determines the Ligand Selectivity in \textit{E.Coli} AMTB Ugur Akgun, Shahram Khademi The transport of ammonia, fundamental to the nitrogen metabolism in all domains of life, is carried out by the Rh/Amt/MEP membrane protein superfamily. The first structure of this family, AmtB from \textit{E.Coli} shows a pathway for ammonia that includes two vestibules connected by a long and narrow hydrophobic lumen. The accepted mechanism for AmtB is to recruit NH$_{4}^{+}$ and conduct neutral NH$_{3 }$by deprotonation of NH$_{4}^{+}$ at the end of periplasmic vestibule. Here we report from various MD simulations performed using a model of trimeric AmtB embedded into POPE lipid bilayer to determine the mechanism of ligands selectivity and conduction in the ammonia channels. Our total more than 500ns simulations reveal that the AmtB periplasmic vestibule prefers NH$_{4}^{+}$ over NH$_{3}$ and CO$_{2}$. And the rate of ammonia conduction is regulated by the motion of the phenyl rings at the bottom of the vestibule. We also report that the conserved D160 is essential for ligand conduction by stabilizing the NH$_{4}^{+}$ at the recruitment site through charge interactions. Our simulations also suggest NH$_{4}^{+}$ most likely releases its proton to the bulk of water as it enters to the hydrophobic lumen. [Preview Abstract] |
Friday, March 19, 2010 8:24AM - 8:36AM |
Y10.00003: Development of electronic structure calculation for biomolecules based on fragment molecular orbital method with three-body term Tomoki Kobori, Shinji Tsuneyuki, Keitaro Sodeyama Recently established fragment molecular orbital (FMO) method enables us to calculate total energy of large molecules very precisely with less computational cost than conventional molecular orbital methods. The method firstly divides a biomolecule into $N$ fragments. Secondly calculations of all fragments and fragment pairs are performed, and finally total energy can be obtained with those of fragments. We recently developed a method of calculating electronic structure of the whole system based on FMO. In this method, called FMO-LCMO, one-electron Hamiltonian of the whole system is constructed by assembling fragment Hamiltonians described by fragment molecular orbitals, with which one-electron energy spectrum and wave functions of the whole system are obtained easily[1]. In this presentation we propose a new scheme of FMO-LCMO based on the three-body FMO method, in which fragment trimers are taken into account in the total energy calculation. It will be demonstrated that the accuracy of the energy spectrum and wave functions of large molecules is drastically improved by considering fragment-fragment interaction through Hamiltonians of fragment trimers \vspace{1.0cm} [1] Chem.Phys.Lett. 476,104-108(2009) [Preview Abstract] |
Friday, March 19, 2010 8:36AM - 8:48AM |
Y10.00004: EPR Spectral Analysis of Vanadyl Model Compounds via Bayesian Inference, Non-linear Least-squares and Statistical Geometry Indra Sahu, Laxman Mainali, Keith Earle Careful analysis is needed to extract quantitative information from experimental EPR spectra. Spectral analysis has been performed on the model compounds: Vanadyl acetylacetonate (VO (acac)$_{2})$ and Vanadyl mesotetraphenyl porphin(VOTPP) via methods of Bayesian Inference, Nonlinear Least-squares (NLS) and Statistical Geometry. The magnetic EPR parameters obtained from the Bayesian inference analysis were held fixed, and the dynamic parameters were fitted during the NLS analysis. From that analysis, we found that the best fit parameters are in good agreement in both methods. The differential entropy and Channel capacity have been calculated for the model systems with and without a Wiener noise filter. The differential entropy was found to be highest at W-band (94 GHz) for both model systems. The channel capacity was highest at K-band (23 GHz) for VO (acac)$_{2}$ and at W-band( 94GHz) for VOTPP. We suggest useful experimental design criteria that can be inferred from these observations. [Preview Abstract] |
Friday, March 19, 2010 8:48AM - 9:00AM |
Y10.00005: EPR Data Analysis on Copper Complexes using Bayesian Inference, Nonlinear-Least Squares and Statistical Geometry Laxman Mainali, Indra Sahu, Keith Earle Accurate values of model parameters are required in order to infer information about structure and dynamics from quantitative lineshape analysis. EPR data analysis has been performed on Copper acetylacetonate (Cu (acac)$_{2})$ and Copper tetraphenyl porphin (CuTPP) using methods of Bayesian Inference, Nonlinear-Least Squares (NLS) and Stastical Geometry. Two site fits for $^{63}$Cu and $^{65}$Cu have also been successfully performed on Cu (acac)$_{2 }$ using the NLS software package. The static and dynamic parameters for the two site fit have been obtained from Bayesian analysis. The best fit parameters determined by different methods are in agreement. The differential entropy and Channel capacity have been calculated for Cu (acac)$_{2}$ and CuTPP with and without a Wiener noise filter. The differential entropy was found to be high in both the mixture ($^{63}$Cu$\backslash \quad ^{65}$Cu) and for individual isotopes at W (94GHz) band for Cu (acac)$_{2}$ and Q (34GHz) for CuTPP. The channel capacity was found to be highest at Q band for both systems which provides a quantifiable metric for the experience of Cu-EPR spectroscopists [Preview Abstract] |
Friday, March 19, 2010 9:00AM - 9:12AM |
Y10.00006: Temperature dependence of gramicidin channel conductance Hyundeok Song, Thomas Beck The gramicidin channel is the smallest known biological ion channel, and it exhibits cation selectivity. Recently, Dr. John Cuppoletti's group at the University of Cincinnati has shown that the gramicidin channel can function at high temperatures with significant currents. This finding may have implications for fuel cell technologies. In order to explore the effect of temperature on channel conductance, we examined the gramicidin system at 300K, 330K, and 360K by computer simulation. Two forms of gramicidin, the head-to-head helical dimer and the intertwined double helix, were examined. Both the decrease of the free energy barrier and the increase of the diffusion of potassium ions inside the gramicidin channel at high temperatures imply an increase of current. We found that higher temperatures also affect the lifetime of hydrogen bonds, the distribution of the bending angle, the distribution of the distance between dimers, and the size of the pore radius for the helical dimer structure. These finding may be related to the gating of the gramicidin channel. [Preview Abstract] |
Friday, March 19, 2010 9:12AM - 9:24AM |
Y10.00007: A statistical model of protein binding in parallel actin bundles Homin Shin, Gregory Grason, Kirstin Purdy Drew, Gerard Wong We propose a coarse-grained lattice model of cross-linking proteins in parallel actin bundles.~Based on this model that captures the interplay between geometrical frustration of binding and the intrinsic flexibility of filaments and linkers, we predict a unique regular ground-state structure of fully cross-linked bundles. We also discuss the linker-dependent thermodynamic transition of actin filaments from their native state to the overtwisted state and map out the ``twist-state'' phase diagram in terms of linker flexibility as well as the chemical potential. A flexible linker regime exhibits a continuous spectrum of intermediate twist states, while a stiff linker regime only allows for untwisted actin filaments and fully overtwisted bundles. Our predictions compare well with small-angle scattering studies of bundles formed in the presence of two types of reconstituted cross-linking proteins, fascin and espin. Additionally, this study reveals how subtle differences in crosslinking agents themselves may be used by cells to achieve self-organized bundles with dramatically different properties. [Preview Abstract] |
Friday, March 19, 2010 9:24AM - 9:36AM |
Y10.00008: Vibrational Dynamics of Atoms in Proteins Derya Vural, Henry Glyde Biological macromolecules expand with increasing temperature and this dynamic expansion is associated with the onset of function. The expansion is typically caused by thermal vibration and thermal diffusion of atom in the proteins. The expansion is usually characterized by the mean square vibrational displacement (MSD), $\langle u^2 \rangle$, of specific atoms such as hydrogen within the macromolecules. We show that the observed expansion and change in slope of $\langle u^2 \rangle$ with temperature at a dynamical transition temperature, $T_D$, can be reproduced within a simple model of the dynamics, an atom vibrating in an anharmonic potential, $V(u)$. Only atomic vibration is incorporated, and given $V(u)$, only the temperature is varied in the model. A simple Gaussian potential or a potential containing a hard wall is particularly effective in producing a significant change in the slope of $\langle u^2 \rangle$ with temperature around $T_D$ as is observed. [Preview Abstract] |
Friday, March 19, 2010 9:36AM - 9:48AM |
Y10.00009: In search of a viable reaction pathway in the chelation of a metallo-protein Frisco Rose, Miroslav Hodak, Jerry Bernholc Misfolded metallo-proteins are potential causal agents in the onset of neuro-degenerative diseases, such as Alzheimer's and Parkinson's Diseases (PD). Experimental results involving metal chelation have shown significant promise in symptom reduction and misfolding reversal. We explore, through atomistic simulations, potential reaction pathways for the chelation of Cu$^{2+}$ from the metal binding site in our representation of a partially misfolded $\alpha $-synuclein, the protein implicated in PD. Our \textit{ab initio} simulations use Density Functional Theory (DFT) and nudged elastic band to obtain the minimized energy coordinates of this reaction. Our simulations include \textit{ab initio} water at the interaction site and in its first solvation shells, while the remainder is fully solvated with orbital-free DFT water representation [1]. Our ongoing studies of viable chelation agents include nicotine, caffeine and other potential reagents, we will review the best case agents in this presentation. \\[4pt] [1] Hodak M, Lu W, Bernholc J. Hybrid ab initio Kohn-Sham density functional theory/frozen-density orbital-free density functional theory simulation method suitable for biological systems. J. Chem. Phys. 2008 Jan;128(1):014101-9. [Preview Abstract] |
Friday, March 19, 2010 9:48AM - 10:00AM |
Y10.00010: A Unified Model of Protein Folding Cooperativity Oleg Vorov, Dennis Livesay, Donald Jacobs Polypeptide and protein folding are cooperative processes currently modeled by different types of microscopic mechanisms. We apply the Distance Constraint Model (DCM) that explains the origin of cooperativity through nonadditivity of conformational entropy. Within the mean-field approximation of uniform constraint density given by Maxwell counting, a unified model emerges that is solved by a transfer matrix method valid for any type of geometry. Heat capacity for the helix/coil transition and protein folding are described markedly well. This work is supported by NIH R01 GM073082 O. K. Vorov, D. R. Livesay, and D. J. Jacobs, Biophysical Journal Volume 97 December 2009 1-10. O. K. Vorov, D. R. Livesay, and D. J. Jacobs, submitted to Phys. Rev. Lett. [Preview Abstract] |
Friday, March 19, 2010 10:00AM - 10:12AM |
Y10.00011: ABSTRACT WITHDRAWN |
Friday, March 19, 2010 10:12AM - 10:24AM |
Y10.00012: Brownian dynamics simulations of insulin microspheres formation Wei Li, Amit Chakrabarti, James Gunton Recent experiments have indicated a novel, aqueous process of microsphere insulin fabrication based on controlled phase separation of protein from water-soluble polymers. We investigate the insulin microsphere crystal formation from insulin-PEG-water systems via 3D Brownian Dynamics simulations. We use the two component Asakura-Oosawa model to simulate the kinetics of this colloid polymer mixture. We first perform a deep quench below the liquid-crystal boundary that leads to fractal formation. We next heat the system to obtain a break-up of the fractal clusters and subsequently cool the system to obtain a spherical aggregation of droplets with a relatively narrow size distribution. We analyze the structure factor S(q) to identify the cluster dimension. S(q) crosses over from a power law q dependence of 1.8 (in agreement with DLCA) to 4 as q increases, which shows the evolution from fractal to spherical clusters. By studying the bond-order parameters, we find the phase transition from liquid-like droplets to crystals which exhibit local HCP and FCC order. This work is supported by grants from the NSF and Mathers Foundation. [Preview Abstract] |
Friday, March 19, 2010 10:24AM - 10:36AM |
Y10.00013: Ionic Moving and Selective Mechanism Through Single Channel of Biomembrane Lingyun Zhang, Peng-Ye Wang The theoretical model is proposed and aimed at analysis for the ionic moving of single channel of biomembrane. For overcoming the weakness of previous theories, we establish the transport equation that not only meet the diffusion requirement but also illustrate the ionic interaction. The coupled equations of the current and electrochemical potential in the single channel of biomembrane is obtained, which can elucidate the fluctuation of membrane current and the conductive mechanism of channel. The theoretical relation of current-voltage, the current-concentration dependence are in agreement with the experimental results. The model quantitatively analysis the electrical behavior and energy effect on the selectivity for different ions. Furthermore, the ionic distribution and energy varied with the channel distance support the binding site model. [Preview Abstract] |
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