Bulletin of the American Physical Society
2005 APS March Meeting
Monday–Friday, March 21–25, 2005; Los Angeles, CA
Session B21: Protein Metastability |
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Sponsoring Units: DBP Chair: Denis Rousseau, Albert Einstein Medical Room: LACC 409A |
Monday, March 21, 2005 11:15AM - 11:27AM |
B21.00001: A DFT-GGA based thermodynamic analysis of the secondary structure of proteins Lars Ismer, Joel Ireta, Matthias Scheffler, J{\"o}rg Neugebauer Studies of the thermodynamic stability of the secondary structure of proteins are important for understanding the protein folding process. We have therefore estimated the free energy change to fold a fully extended structure (FES) into the $\alpha$-helical conformation for isolated infinite poly-glycine (Gly) and -alanine (Ala) chains. The calculations have been performed employing DFT-GGA, a plane-wave pseudo-potential approach and the harmonic approximation. Our results reveal [1], that this approach leads to a significantly improved description of thermodynamic data with respect to previous studies based on empirical force fields. Further we find, that the enthalpy to transform an $\alpha$-helix into an FES strongly reduces with increasing temperature: at room temperature the free energy difference for Gly is close to zero within the numerical error bar (0.5 kcal/mol), whereas for Ala the $\alpha$-helix is by 1.0 kcal/mol more stable. We conclude, without recoursing to any empirical input parameters, that an isolated Ala-FES will even at room temperature spontaneously fold into an $\alpha$-helix.\\ \\ 1. L. Ismer, J. Ireta, S. Boeck and J. Neugebauer submitted to Phys. Rev. E [Preview Abstract] |
Monday, March 21, 2005 11:27AM - 11:39AM |
B21.00002: Continuum Theory of Beta-Sheet Ribbons. Rouzbeh Ghafouri We present a continuum description for the $\beta $-sheet ribbons encountered in amyloid fibrils, allowing both stretching and bending of the ribbon in response to chiral twist. The theory leads to a non-linear variant of the Worm-Like Chain (WLC). At a critical value of the ratio of the bending and stretching moduli, the Foppl-von K\'{a}rm\'{a}n Number, we encounter a continuous \textit{buckling transition} from a straight Helicoid to a Spiral Ribbon. Two of the three persistence lengths of the ribbon become very short at the transition point indicating strong thermal shape fluctuations. The transition becomes discontinuous if the ribbon width is treated as a free thermodynamic variable. [Preview Abstract] |
Monday, March 21, 2005 11:39AM - 11:51AM |
B21.00003: Coarse-Grained Models of Entropic Allostery in Proteins Rhoda Hawkins, Tom McLeish Allosteric proteins are involved in many signalling processes in molecular biology. As an alternative to conformational change in the mean static structure, it has been suggested that the information of ligand binding may be transmitted to a distant site across an allosteric protein by changes to the pattern of the internal dynamics of the protein. We explore how ligand binding may change the intramolecular vibrational entropy and free energy through coarse-grained models of this ``entropic allostery''. We consider coarse-grained models of various repressor proteins such as the lac repressor. We also investigate allostery in alpha helical coiled-coils, found in proteins such as the dynein molecular motor and bacteria chemotaxis receptors. [Preview Abstract] |
Monday, March 21, 2005 11:51AM - 12:03PM |
B21.00004: Artificial Allosteric Control of Proteins Giovanni Zocchi, Brian Choi We built an artificial mechanism of allosteric control of a protein, based on mechanical stress. The Maltose-Binding Protein (MBP) of E. coli undergoes a conformational change upon binding maltose. Introducing a mechanical stress favoring one or the other conformation will therefore alter the binding affinity for the substrate. We have constructed a chimera where the two lobes of the maltose binding protein are covalently coupled to the ends of a DNA oligomer. The mechanical tension on the protein is provided by the bending elasticity of the DNA, and is controlled by exploiting the difference between single stranded and double stranded DNA. We report that the binding affinity of MBP for maltose is significantly altered by the tension, which was varied by allowing DNA oligomers of various lengths to hybridize to the DNA of the chimera. By the same method, we control the enzymatic activity of a second protein: Guanylate Kinase from Mycobacterium Tuberculosis. This study exemplifies a general strategy to introduce artificial control elements in the function of proteins. [Preview Abstract] |
Monday, March 21, 2005 12:03PM - 12:15PM |
B21.00005: Theoretical study of metal binding in the Prion protein Jianping Pan, Daniel Cox, Rajiv Singh We have used the SIESTA density functional theory code to study binding of divalent transition metal ions (Cu,Ni,Zn,Mn) to the two known types of attachment sites of the prion protein, one (I) outside the misfolded region, the other (II) within the misfolded region. Our binding energy trend for the (I) site is E$_{B}$(Cu)$>>$E$_{B}$(Ni)$>$E$_{B}$(Zn)$>>$E$_{B} $(Mn) in agreement with affinities measured \textit{in vitro}. We find the Cu binding stronger in the (II) site to be stronger than that of the (I) site, in agreement with separate experiments, and propose a new structure for site (II) with bound Cu which is \textit{incompatible }with a recently proposed $\beta $-helix structure, suggesting a possible correlation between copper deficiency and misfolding of the prion protein compatible with observations of copper depletion in infected neurons. [Preview Abstract] |
Monday, March 21, 2005 12:15PM - 12:27PM |
B21.00006: Kinetic and Stochastic Models of 1D yeast ``prions" Kay Kunes, Daniel Cox, Rajiv Singh Mammalian prion proteins (PrP) are of public health interest because of mad cow and chronic wasting diseases. Yeasts have proteins, which can undergo similar reconformation and aggregation processes to PrP; yeast ``prions" are simpler to experimentally study and model. Recent in vitro studies of the \textit{SUP}35 protein (1), showed long aggregates and pure exponential growth of the misfolded form. To explain this data, we have extended a previous model of aggregation kinetics along with our own stochastic approach (2). Both models assume reconformation only upon aggregation, and include aggregate fissioning and an initial nucleation barrier. We find for sufficiently small nucleation rates or seeding by small dimer concentrations that we can achieve the requisite exponential growth and long aggregates. [Preview Abstract] |
Monday, March 21, 2005 12:27PM - 12:39PM |
B21.00007: Solvent Effect on the Melting of Biopolymers Lingyun Zhang, An-Chang Shi The melting process of biopolymers has been studied using self- consistent field theory of polyelectrolyte system. The chain statistics, polymer-solvent and electrostatic interactions are described by a set of coupled nonlinear equations. In particular, the effect of counterions on biopolymer is included in the nonlinear Poisson-Boltzmann equation. The influence of the solvent on the conformational behavior of biopolymers has been studied. Starting from the free energy of system, the thermodynamic properties of biopolymers are obtained. The theoretical results for the denatured temperature on the counterion concentration are in agreement with experiments. The relationship between the specific heat and temperature has been obtained numerically, which is used to explain the experimentally observed coefficient of linear specific heat at low temperature. [Preview Abstract] |
Monday, March 21, 2005 12:39PM - 12:51PM |
B21.00008: Coupling between Protein and Solvent Dynamics Taner E. Dirama, Gustavo A. Carri Trehalose and glycerol are commonly used to preserve biopolymers like proteins against denaturation and its consequent loss of activity. The molecular mechanism behind the preservation ability of such bio-protective agents is not fully understood at present. In this talk, we present a Molecular Dynamics simulation study of the short time ($<$1 ns) dynamics of lysozyme in trehalose and glycerol. The analysis of the dynamic structure factor and incoherent scattering function shows that the dynamics of lysozyme follows the one of the solvent. However, the effectiveness of this coupling decreases as we move away from the surface of the protein. In addition, we find that trehalose provides a better suppression of the dynamics than glycerol at temperatures above 250 K whereas glycerol is more effective at low temperatures, in agreement with experimental observations. Our hydrogen bonding analysis shows that trehalose forms stronger hydrogen bonds with lysozyme at high temperatures while glycerol has more robust hydrogen bonds at low temperatures. This correlation between hydrogen bond behavior and the dynamics suggests that hydrogen bonding between the protein and the solvent plays an important role in the suppression of the dynamics. [Preview Abstract] |
Monday, March 21, 2005 12:51PM - 1:03PM |
B21.00009: Conformational changes of adsorbed proteins Scott Allen, Rickey Yada, John Dutcher The adsorption of bovine serum albumin (BSA) and pepsin to gold surfaces has been studied using surface plasmon resonance (SPR). Proteins are adsorbed from solution onto a gold surface and changes in the conformation of the adsorbed proteins are induced by changing the buffer solution. We selected pH and ionic strength values for the buffer solutions that are known from our circular dichroism measurements to cause conformational changes of the proteins in bulk solution. We find that for both BSA and pepsin the changes in conformation are impeded by the interaction of the protein with the gold surface. [Preview Abstract] |
Monday, March 21, 2005 1:03PM - 1:15PM |
B21.00010: Self-Assembly of Natural Silk Fibroin under Osmotic Stress Sungkyun Sohn, Tamako Hata, Helmut H. Strey, Samuel P. Gido Osmotic stress method was applied to investigate the supramolecular self-assembly behavior of natural silk fibroin within the gland. As with the experiments on re-generated silk fibroin, poly(ethylene glycol) 8K was used to apply an osmotic stress of 0.2-7.6 MPa to the gland of Bombyx mori silkworm, in vitro. Fibroin samples were extracted from the fibroin-dominant, water-soluble posterior region, and from three different parts in the middle region of the gland. Calcium chloride of 0.01 M was added to each stressing solution to balance the physiological salt content of the sample. Microscopic and thermodynamic details of this self-assembly process along the spinline have been assessed by wide angle X- ray diffraction, optical microscopy, etc. It is apparent that as osmotic stress increases, isotropic silk fibroin molecules in the posterior region are assembled together to form a water-soluble crystalline mesophase known as silk-I. Further increases in osmotic stress induce an anti- parallel beta-sheet structure known as silk-II. [Preview Abstract] |
Monday, March 21, 2005 1:15PM - 1:27PM |
B21.00011: Quantifying Stability-Flexibility Relationships in Proteins Donald Jacobs, Jeremy Hules, Shelley Green, Dennis Livesay Given a 3D protein structure, thermodynamic properties are calculated using a Distance Constraint Model$^{1}$ (DCM) within a mean-field treatment in practical computational times. Using a 3 free parameter free-energy decomposition scheme in terms of distinct interaction types, non-additivity of component entropies are accounted for by using network rigidity. Over a diverse set of proteins, the essential features of heat capacity agree well with differential scanning calorimetry measurements$^{2}$. Landau free energy curves are obtained as a function of a global flexibility order parameter, and used as a reaction coordinate. Comparing the rigidity transition to the thermodynamic transition state allows compactness of the transition state to be inferred. Correlation in flexibility between backbone residues gives insight into folding pathways and allosteric effects in the native state. $^{1 }$D.J. Jacobs, et. al., Phys. Rev. E 68:061109 (2003) $^{2}$ D.R. Livesay, et. al., FEBS Lett. 576:468-476 (2004) [Preview Abstract] |
Monday, March 21, 2005 1:27PM - 1:39PM |
B21.00012: Low Frequency Light Scattering Spectroscopy of Lysozyme in Solution Alfons Schulte, Ronald Gebhardt, Walter Schirmacher Low-frequency Raman and Brillouin spectra provide a probe for dynamic coupling of protein motions to the solvent. We report on polarization resolved measurements of the light scattering spectrum of lysozyme in aqueous solution over the frequency range from 1 GHz to 20 THz and temperatures from 275 and 300 K. The dynamics extend over more than 3 decades and show temperature independent peaks at 1.5 THz for water and at 2 THz for the protein solution. The alpha-relaxation peaks are observed between 2 and 40 GHz, and these move to lower frequencies with decreasing temperature due to slowing down of structural relaxation. At frequencies below 2 GHz the protein solution shows an excess of quasielastic scattering as measured on both the Stokes and the Anti-Stokes side of the Rayleigh line. The excess intensity is discussed with respect to protein rotational motions and relaxations of the bound water. The apparent compressibility of the protein increases the frequency of the Brillouin line. [Preview Abstract] |
Monday, March 21, 2005 1:39PM - 1:51PM |
B21.00013: Terahertz Dielectric Response Measurements of the Protein Glass Transition R. Kao, J. -Y. Chen, J.R. Knab, A.G. Markelz Collective vibrational modes associated with protein conformational fluctuations lay in the far infrared or terahertz frequency range (1-200 cm$^{-1})$. Numerous dynamical measurements on proteins have found a transition at $\sim $ 200 K, referred to as a protein glass transition [D. Ringe, G.A. Petsko, Biophys. Chem. \textbf{105}, 667--680 (2003) ]. For temperatures below 200 K the collective mode response is harmonic, whereas above 200 K the collective mode response is anharmonic. We examine how this temperature dependent dynamical transition effects the terahertz dielectric response for both solutions and hydrated films of cytochrome c and bacteriorhodopsin using terahertz time domain spectroscopy. This work was supported by ACS grant PRF 39554-AC6, NSF CAREER grant PHY-0349256 and NSF IGERT grant DGE0114330. [Preview Abstract] |
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