Bulletin of the American Physical Society
2008 APS March Meeting
Volume 53, Number 2
Monday–Friday, March 10–14, 2008; New Orleans, Louisiana
Session U40: Biomolecular Computation |
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Sponsoring Units: DBP Chair: Margaret Cheung, University of Houston Room: Morial Convention Center 232 |
Thursday, March 13, 2008 8:00AM - 8:12AM |
U40.00001: Hydrophobic polymers in nano-sized water droplets Buddhi Tilakaratne, Samina Masood, Margaret Cheung As simulations of biopolymers take place in confined and tight spaces, such as protein folding in the interior of bacteria chaperones or the exit tunnels of ribosomes, quantitative analyses of the confinement effects on both biopolymers and solvent molecules become the center of attention as the solvent-mediated interactions are too profound to solve analytically. We are in the progress to investigate the solvation of hexane molecules in various nano-sized water droplets. Free energy profiles for a single hexane molecule in droplets show that the droplet surfaces are favored. Averaged configurations of hexane molecules at the interior and the surface are computed using the umbrella sampling methods. The implications of our results for protein stability in confined spaces will be discussed. [Preview Abstract] |
Thursday, March 13, 2008 8:12AM - 8:24AM |
U40.00002: A classical density functional for water David Roundy, Dennis Jackson We present a classical density functional for water that represents the short-range repulsive interaction using the fundamental-measure-theory hard-sphere functional. The parameters of this functional are chosen to reproduce the experimental liquid density, bulk modulus and surface tension of water, and to ensure coexistance of liquid and vapor phases. This functional inherits from the FMT functional its accurate description of reduced-dimensionality configurations. We will present computations of the hydrophobic hydration energy of hard-sphere solutes, demonstrating an accurate description at both large and small length scales. [Preview Abstract] |
Thursday, March 13, 2008 8:24AM - 8:36AM |
U40.00003: Hydrophobic interactions at molecular scale. Dubravko Sabo, Sameer Varma, Susan Rempe, Marcus Martin Structural and thermodynamic properties are investigated for one of the simplest hydrophobic solutes, a hydrogen molecule solvated in liquid water. The structural properties are calculated using different representations of the intermolecular interactions within molecular dynamics, Monte Carlo and ab initio molecular dynamics simulation frameworks. Although structural details differ in the radial distribution functions obtained by different force fields all approaches agree that 16 water molecules coordinate hydrogen. The thermodynamic properties are investigated using Monte Carlo molecular simulation and the quasichemical theory of liquids. Results show that the net hydration free energy arises from a balance between chemical association and molecular packing. Additionally, the results suggest the molecular packing is almost equally driven by unfavorable enthalpic and entropic components. [Preview Abstract] |
Thursday, March 13, 2008 8:36AM - 8:48AM |
U40.00004: Computing absolute binding affinities via non-equilibrium unbinding simulations F. Marty Ytreberg We demonstrate that non-equilibrium unbinding simulations can be used to accurately estimate equilibrium absolute binding affinities ($\Delta G$). Utilizing the FKBP protein bound to two different ligands we estimate $\Delta G$ within less than 1.0 kcal/mol of experimental values. The methodology is straight-forward, requiring no modification to many modern molecular simulation packages. The approach makes use of a physical pathway, eliminating the need for complicated alchemical decoupling schemes. These results suggest that non-equilibrium simulation could provide a viable means to accurately estimate protein-ligand binding affinities. [Preview Abstract] |
Thursday, March 13, 2008 8:48AM - 9:00AM |
U40.00005: Macromolecular crowding effects on Brownian motion of protein GB1 Antonios Samiotakis, Margaret Cheung The effect of macromolecular crowding in the interior of a cell plays an important role in protein folding dynamics and its stability. In the present work the dependence of diffusion coefficients of the macromolecule on various crowding conditions is studied using a coarse-grained representation of protein G B1 domain that includes Go-like interactions. Using Brownian dynamics simulations, diffusion coefficients are computed as a function of the volume fraction of crowders $\phi _c $ and the ratio $\lambda$ of the sizes of the crowder over that of protein. Deviation from linear Stokes-Einstein relation will be discussed. [Preview Abstract] |
Thursday, March 13, 2008 9:00AM - 9:12AM |
U40.00006: Core-Shell Model of Folding-Unfolding Transitions (UFT) in Proteins Svetlana Aroutiounian There are $\sim $10$^{N}$ conformations for a protein of length $N$ to sort out randomly in search of lowest free energy state. Can protein folding be simple and fast? Core-shell model introduces principles, proposes mechanisms and scores residues of fast, reversible UFT in protein. According to it, during UFT the realm of intra-residual interactions leads the residue motion. The scaffold of hydrophilic residues forms external shell of unstructured, tube-like protein in unfolded state, just as the hydrophobic residues form internal scaffold -- core, of the protein in folded state. As UFT proceeds, residue slides into lowest-score position permitted by its structure. Model accounts for experimentally observed features of UFT. It is based on three principles: 1) During UFT protein is \textit{virtual} - its features or structure are inferred only statistically and with limited precision; 2) Mechanism of UFT memory is not longitudinal, but \textit{transverse}; 3) Native design overrides specific features of residues - the alphabet of amino acids assumes an \textit{intrinsic} score-function. Per-residue mechanism of UFT is proposed and score-function is described. Difference graphs of transitional score-function and average genome-wide abundance index show that our score-function \textit{is} the order parameter of UFT in protein and by virtue of being it, reveals transitional key residues. It echoes the multiple-tier and funnel concepts of FEL perspective. Monte Carlo simulations of UFT in myoglobin illustrate the idea. [Preview Abstract] |
Thursday, March 13, 2008 9:12AM - 9:24AM |
U40.00007: Potential of mean force of Glycophorin A alpha-helix dimerization Lorant Janosi, Manolis Doxastakis Thansmembrane proteins recognition and association plays a crucial role in their assembly and function. In spite of the extensive studies, these processes are only partially understood. We investigate the association of the model transmembrane alpha-helices by means of potential of mean force (PMF) calculations. The model system consists of a pair of alpha-helices of Glycophorin A, a system that experimentally exhibits dimerization in lipid membranes. Using established coarse-grained models, we developed a Monte Carlo methodology to overcome sampling limitations imposed by long characteristic times present in lipid membrane simulations. A combination of the Expanded Ensemble Density of States formalism and hybrid molecular dynamics allow for efficient and accurate calculations on the association of the helices. The methodology developed offers unique insight into the mechanism of dimerization and provides a means to evaluate the effect of lipid composition and temperature on the association of Glycophorin A. [Preview Abstract] |
Thursday, March 13, 2008 9:24AM - 9:36AM |
U40.00008: Monte Carlo Simulations with reference interaction site model theory for simulating peptide molecules in aqueous solution Ayori Mitsutake, Yutaka Maruyama, Takashi Imai, Masahiro Kinoshita, Yuko Okamoto, Fumio Hirata We have developed Monte Carlo simulations with reference interaction site model theory for simulating proteins in aqueous solution. The reference interaction site model theory based on the liquid theory of statistical mechanics can treat solvent effect with solvent molecular shape and estimate solvation free energy around proteins. We have developed simulation algorithms which combine with generalized-ensemble algorithms and reference interaction site model theory. We showed results of a simulated annealing Monte Carlo simulation, a multicanonical Monte Carlo simulation, and a replica-exchange Monte Carlo simulation with one dimensional reference interaction site model theory for Met-Enkephalin, a penta-peptide [1,2,3]. Recently we have performed a Monte Carlo simulation with three-dimensional reference interaction site model theory for simulating C-peptide in aqueous solution. We will describe these attempts and discuss results of these simulations. [1] M. Kinoshita, Y. Okamoto, and F. Hirata, \textit{J. Am. Chem. Soc.}\textbf{ 120}, 1855 (1998) [2] A. Mitsutake, M. Kinoshita, Y. Okamoto, and F. Hirata, \textit{Chem. Phys. Lett.} \textbf{329}, 295 (2000) [3] A. Mitsutake, M. Kinoshita, Y. Okamoto, and F. Hirata, \textit{J. Phys. Chem. B} \textbf{108}, 19002 (2004) [Preview Abstract] |
Thursday, March 13, 2008 9:36AM - 9:48AM |
U40.00009: Glassy protein dynamics and gigantic solvent reorganization energy of plastocyanin David LeBard, Dmitry Matyushov This work focuses on the results of extensive explicit solvent Molecular Dynamics simulations of plastocyanin, a blue copper electron transfer protein involved in natural photosynthesis. Simulation data indicate that low-frequency non-ergodic fluctuations of the protein matrix tethered to the hydrating water are responsible for a very broad distribution of the vertical energy gaps of one-electron protein reduction/oxidation. The width of the corresponding free energy surfaces yields a reorganization free energy far larger than previously reported for any organic, inorganic, or biological chromophores. However, the Stokes shift is not affected by these slow motions and can be calculated from the polarization response function of the dipolar solvent using microscopic solvation models. The glassy nature of the protein-water interface breaks the direct link between the Stokes shift and the reorganization energy from equilibrium (ergodic) electron transfer theories. This suggests a mechanism that accounts for electron transfer in natural proteins, which are characterized by a low reaction free energy combined with a low activation barrier. [Preview Abstract] |
Thursday, March 13, 2008 9:48AM - 10:00AM |
U40.00010: Modeling low frequency vibrational modes of large biomolecules Otto Sankey, Eric Dykeman Mechanical oscillations of proteins in their native state are relevant to understanding the flexibility of the protein assembly, the binding of substrates, the mechanical action involved in enzymatic activity, and the vibrational response to light scattering. Often, only the low frequency modes are of interest and coarse grained methods or other approximations are used due to the large size of the dynamical matrix. We introduce a computational approach, which exploits the methodology from electronic structure Order N methods, to find the vibrational modes below some frequency threshold (analogous to a Fermi-level in electronic structure theory). The approach allows systems to be described in atomistic detail. We use a generalized Born force field to model the interactions. Examples of normal modes for icosahedral viruses (e.g. satellite tobacco necrosis virus), tubular viruses (e.g. M13), and enzymes (e.g. lysozyme, HIV-protease, alpha-lytic protease) will be discussed. This effort is motivated by recent experimental work to produce high amplitude vibrations of viruses from impulsive stimulated Raman scattering. [Preview Abstract] |
Thursday, March 13, 2008 10:00AM - 10:12AM |
U40.00011: Monte Carlo simulations of Protein Adsorption Sumit Sharma, Sanat K. Kumar, Georges Belfort Amyloidogenic diseases, such as, Alzheimer's are caused by adsorption and aggregation of partially unfolded proteins. Adsorption of proteins is a concern in design of biomedical devices, such as dialysis membranes. Protein adsorption is often accompanied by conformational rearrangements in protein molecules. Such conformational rearrangements are thought to affect many properties of adsorbed protein molecules such as their adhesion strength to the surface, biological activity, and aggregation tendency. It has been experimentally shown that many naturally occurring proteins, upon adsorption to hydrophobic surfaces, undergo a helix to sheet or random coil secondary structural rearrangement. However, to better understand the equilibrium structural complexities of this phenomenon, we have performed Monte Carlo (MC) simulations of adsorption of a four helix bundle, modeled as a lattice protein, and studied the adsorption behavior and equilibrium protein conformations at different temperatures and degrees of surface hydrophobicity. To study the free energy and entropic effects on adsorption, Canonical ensemble MC simulations have been combined with Weighted Histogram Analysis Method(WHAM). Conformational transitions of proteins on surfaces will be discussed as a function of surface hydrophobicity and compared to analogous bulk transitions. [Preview Abstract] |
Thursday, March 13, 2008 10:12AM - 10:24AM |
U40.00012: Complexation of Flavonoids with Iron: Structure and Optical Signatures Jun Ren, Sheng Meng, Ch. E. Lekka, Efthimios Kaxiras Flavonoids exhibit antioxidant behavior believed to be related to their metal ion chelation ability. We investigate the complexation mechanism of several flavonoids, quercetin, luteolin, galangin, kaempferol and chrysin with iron, the most abundant type of metal ions in the body, through first- principles electronic structure calculations based on Density Functional Theory (DFT). We find that the most likely chelation site for Fe is the 3-hydroxyl-4-carbonyl group, followed by 4- carbonyl-5-hydroxyl group and the 3'-4' hydroxyl (if present) for all the flavonoid molecules studied. Three quercetin molecules are required to saturate the bonds of a single Fe ion by forming six orthogonal Fe-O bonds, though the binding energy per molecule is highest for complexes consisting of two quercetin molecules and one Fe atom, in agreement with experiment. Optical absorption spectra calculated with time- dependent DFT serve as signatures to identify various complexes. For the iron-quercetin complexes, we find a redshift of the first absorbance peak upon complexation in good agreement with experiment; this behavior is explained by the narrowing of the optical gap of quercetin due to Fe(d)--O(p) orbital hybridization. [Preview Abstract] |
Thursday, March 13, 2008 10:24AM - 10:36AM |
U40.00013: When Cells Collide: A Model for Cell-Assisted Cell Growth based on Direct Contacts Carl Franck, Wui Ip, Albert Bae, Nathan Franck, Elijah Bogart, Thanhbinh Thi Le Although intercellular communication is frequently viewed as involving the transport of small molecules through an intracellular fluid medium, biologists have proposed chemical signaling with chemical specificity due to chemical recognition through direct contacts. Considering the collective computation behind the decision of a cell to divide when it senses the presence of a sufficient number of like neighbors, we offer a model for the transition from slow to exponential growth in shaken suspension cell culture of the model eukaryote, \textit{Dictyostelium discoideum}. Besides exploring an elegantly simple example of multicellular life, this discussion might well prove useful in considering the limits of cell culture on small spatial scales as required for contemporary massively parallel biotechnology. [Preview Abstract] |
Thursday, March 13, 2008 10:36AM - 10:48AM |
U40.00014: Do Porins Pass CAPs? C.B. Hanna, D.A. Pink, T.A. Gill, T.J. Beveridge, B.E. Quinn, J.J. Durrant, M.H. Jericho The cationic antimicrobial peptide (CAP) protamine is known to inhibit bacterial survival (Pink et al., \textit{Langmuir} \textbf{19}, 8852 (2003), and references therein), but the mechanism of attack is as yet undetermined. For Gram-negative bacteria, two pathways have been proposed: (a) self-promoted uptake, and (b) passage through porins. Here, we study the latter possibility, and model part of the outer membrane of a Gram-negative bacterium in an aqueous solution containing multivalent ions and CAPs. The intent is to determine whether CAPs could pass through porins and, if so, what aspects of external (e.g., ionic concentration) and internal (e.g., porin and O-sidechain characteristics) parameters affect their passage. This study is accomplished via Monte Carlo computer simulations of a ``minimal model'' of the outer membrane of a Gram-negative bacterium with an embedded porin. [Preview Abstract] |
Thursday, March 13, 2008 10:48AM - 11:00AM |
U40.00015: Multimode Analysis of SHG Signal from Complex Biological Systems: Parameterization of Regional and Global Features. Clayton Bratton, Karen Reiser, Andre Knoesen, Diego Yankelevich, Mingshi Wang, Israel Rocha-Mendosa We have continued development of our novel computational approach for quantifying structural disorder in biomolecular lattices with nonlinear susceptibility based on analysis of polarization-modulated second harmonic signal. Local disorder at the level of molecular organization is identified using a novel signal-processing algorithm sufficiently compact for near real-time analysis. Global and regional disorder within the biostructure is characterized using two-dimensional wavelet transform of the magnitude and phase of the second harmonic signal. Results suggest our signal processing method represents a robust, scaleable tool that allows us to detect both regional and global alterations in signal characteristics of biostructures with a high degree of discrimination. [Preview Abstract] |
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