Bulletin of the American Physical Society
2008 APS March Meeting
Volume 53, Number 2
Monday–Friday, March 10–14, 2008; New Orleans, Louisiana
Session W18: Focus Session: Dynamics of Nucleic Acid-Protein Interactions |
Hide Abstracts |
Sponsoring Units: DPOLY DBP Chair: Ferenc Horkay, National Institutes of Health Room: Morial Convention Center 210 |
Thursday, March 13, 2008 2:30PM - 3:06PM |
W18.00001: Single-Molecule Dynamics of a DNA Aptamer Targeting VEGF Protein Invited Speaker: Single-molecule fluorescence resonance energy transfer (SMFRET) and SMFRET autocorrelation analysis were used to examine structural fluctuations in a DNA aptamer that binds and exhibits inhibition activity towards the vascular endothelial growth factor (VEGF) protein, a protein that is involved in macular degeneration. The aptamer's most stable conformation contains 4 Watson-Crick base pairs, resulting in only a shallow negative potential relative to the unfolded state. The weakly stable folded state and the manifold of unfolded structures quickly interconvert. In contrast, in the presence of the VEGF target, the aptamer folding rate constant decreases and the fluctuations in both the unfolded and folded states decrease in frequency, but are not eliminated. A possible relationship between activity and aptamer flexibility is discussed [Preview Abstract] |
Thursday, March 13, 2008 3:06PM - 3:18PM |
W18.00002: Thermal Disorder Effect on the DNA Electronic Structure Alexander Balaeff, Elizabeth Hatcher, Shahar Keinan, Ravindra Venkatramani, David Beratan We address the effect of the thermal dynamics of DNA structure on the energy and localization of the DNA electronic orbitals. Structural ensembles are generated for several DNA sequences by molecular dynamics simulations employing CHARMM and AMBER force fields. In the shortest sequences studied (CATG, GAAG, GATG, GAG), the highest occupied molecular orbitals (HOMOs) expectedly reside on the guanines (Gs), yet in a significant number of the structures the orbitals are observed to be delocalized between the Gs and the bridging adenines (As). Adding more Gs to the ends of the sequence expectedly shifts the orbitals toward the G clusters, yet the amount of orbital delocalization to the bridge is still significant. These observations suggest that a) contrary to the predominant view in the field, G-to-A thermal hopping may contribute significantly to the charge transfer in DNA even in the short-distance range, and b) the contribution of DNA structural fluctuations to triggering the charge transfer is as significant as that resulting from the ion gating mechanism. [Preview Abstract] |
Thursday, March 13, 2008 3:18PM - 3:30PM |
W18.00003: Thermodynamic Restriction on Evolutionary Optimization of Transcription Factor Proteins Alexander Grosberg, Longhua Hu, Robijn Bruinsma Conformational fluctuations are believed to play an important role in the process by which transcription factor proteins locate and bind their target site on the genome of a bacterium. Using a simple model, we show that the binding time can be minimized, under selective pressure, by adjusting the spectrum of conformational states so that the fraction of time spent in more mobile conformations is matched with the target recognition rate. The associated optimal binding time is then within an order of magnitude of the limiting binding time imposed by thermodynamics, corresponding to an idealized protein with instant target recognition. Thus, we claim that it is possible for the overall binding rate of a transcription factor to approach the theoretical limiting value but only by a suitable choice of energy spectrum of conformational sub-states, and only if the dimensionless binding rate is of the order of one, or larger than one, where dimensionless binding rate is determined as the product of binding rate and the average time spent by the protein on one DNA base pair in one tour of 1D sliding along DNA. Numerical estimates suggest that typical bacteria operate in this regime of optimized conformational fluctuations. [Preview Abstract] |
Thursday, March 13, 2008 3:30PM - 3:42PM |
W18.00004: Electron affinities of nucleobases, glycine and their complexes Ed S. Chen, Edward C. Chen The electron affinities of adnenine, guanine, and the amino acids except for glycine have not been measured in the gas phase. New valence state electron affinities of the subject molecules are reported from reduction potentials and literature anion photoelectron spectra. These are supported by quantum mechanical calculations. Multiple negative ion potential energy curves are calculated to consolidate reduction potentials, electron impact spectra in helium nanodroplets, negative ion mass spectra, electron transmission spectra, electron spin resonance data for DNA, A method of measuring negative valence state electron affinities using ESR data is proposed. The adiabatic electron affinities are: in eV~ Adenine, 1.08(5), Guanine, 1.65(10), Cytosine, 1.04(5), Thymine, 0.98(5), Uracil, 0.99(5), Glycine, 0.50(5) Adenine: thymine 1.40(5) eV. Excited dipole bound and valence state electron affinities are also identified. [Preview Abstract] |
Thursday, March 13, 2008 3:42PM - 3:54PM |
W18.00005: Chemical physics of DNA packaging in a nucleosome core particle Andrew Spakowitz, Bariz Sudhanshu The fundamental unit of packaged DNA, the nucleosome core particle, contains 146 base pairs of DNA wrapped 1.7 times around a cationic protein complex called the histone octamer. A string of nucleosomes is organized into higher-order structures at several hierarchical levels to form chromatin, a remarkable complex that is compact yet maintains accessibility for gene expression. We develop a theoretical model of the nucleosome core particle in order to extract detailed quantitative information from single-molecule measurements of a single nucleosome under tension. We employ the wormlike chain model to describe the DNA strand as a thermally fluctuating polymer chain. The chain adsorbs on a spool that represents the histone octamer. This model is directly compared to single-molecule experiments conducted in Carlos Bustamante's lab; we find good agreement between our theory and the experimental data. Our model reveals the mechanism that underlies structural transitions that are apparent in the experimental measurements and predicts the conditions where these transitions occur. We proceed to construct a free energy surface to predict the dynamic response in a single-molecule experiment with a time-dependent rate of unwinding the nucleosome. The combination of single-molecule experiments and our theoretical modeling gives detailed information about the specific interactions between DNA and histone proteins. [Preview Abstract] |
Thursday, March 13, 2008 3:54PM - 4:06PM |
W18.00006: DNA analysis in polymer nanofluidic devices Lasse Thamdrup, Anna Klukowska, Anders Kristensen Inexpensive polymer biochips with nanofluidic channels, for investigating confined DNA, are presented. The biochips are fabricated by thermal imprint in polymethyl methacrylate (PMMA) using a 4 inch diameter two-level hybrid stamp. The fluidic structures were sealed using thermal polymer fusion bonding. The stamp has nanometer- and micrometer-sized protrusions defined in a thermally grown SiO$_{2}$ layer and the sol-gel process derived duromeric polymer Ormocomp respectively. A durable chlorosilane based antistiction coating was applied by molecular vapour deposition. The polymer biochips were benchmarked against conventional fused silica based devices, by extending T4 GT7 bacteriophage DNA inside the nanochannels. The measured average extension length amounts to 20{\%} of the full contour length with a standard deviation of 4{\%}. These results are in good agreement with results obtained in fused silica devices. [Preview Abstract] |
Thursday, March 13, 2008 4:06PM - 4:18PM |
W18.00007: Separation of long DNA molecules through cleavage of hydrogen bonds under a stretching force Lizeng Gao, Jiamin Wu, Jianzhong Wu, Di Gao We report that long DNA molecules of different lengths can be separated under a stretching force by cleaving hydrogen bonds that tether one end of the DNA to a substrate. This separation method can be implemented with a simple direct current electric field, does not require separation matrices, and in principle has no upper limit on the length of the DNA that can be efficiently separated. We here demonstrate efficient separation of lambda DNA (48,502 base pairs) from human genomic DNA ($>$ 100,000 base pairs) using this method. [Preview Abstract] |
Thursday, March 13, 2008 4:18PM - 4:30PM |
W18.00008: Self-organized DNA/F-actin gels: entangled networks of nematic domains with tunable density John Butler, Olena Zribi, Ivan Smalyukh, Ghee Hwee Lai, Ramin Golestanian, Thomas Angelini, Gerard Wong We examine mixtures of DNA and F-actin as a model system of like-charged rigid rods and flexible chains. Confocal microscopy reveals the formation of elongated nematic F-actin domains reticulated via defect-free vertices into a network, all embedded in a mesh of random DNA. Synchrotron x-ray scattering results indicate that the DNA mesh squeezes the F-actin domains into a nematic state via the osmotic pressure of uncondensed counterions, so that the inter-actin spacing within the domains decreases with increasing DNA concentration. These observations are consistent with arguments based on electrostatics and nematic elasticity. [Preview Abstract] |
Thursday, March 13, 2008 4:30PM - 4:42PM |
W18.00009: Histone code or not? Combinatorial pattern analyses of histone modifications Chongzhi Zang, Weiqun Peng, Zhibin Wang, Dustin E. Schones, Artem Barski, Suresh Cuddapah, Kairong Cui, Tae-Young Roh, Keji Zhao, Jeffrey Rosenfeld, Michael Zhang Eukaryotic genomes are organized into chromatin, the structure of which plays critical role in the program of gene expression. Chromatin structure and function is regulated by a myriad of posttranslational modifications on histone tails of the nucleosomes, the fundamental unit of chromatin. It remains unclear how different modifications interact. Based on high- resolution genomic maps of close to 40 histone methylations and acetylations in human T-cells obtained experimentally by ChIP- Seq technique, we investigated the combinatorial patterns of histone modifications at gene promoter regions. We found that a very limited number of patterns dominate. Modifications within a pattern are strongly correlated and each pattern is associated with a distinct gene expression distribution. Our results suggest that it is the patterns rather than the individual modifications that affect the downstream readout. [Preview Abstract] |
Thursday, March 13, 2008 4:42PM - 4:54PM |
W18.00010: Changes of histone modification landscape in cell differentiation Weiqun Peng, Chongzhi Zang, Kairong Cui, Tae-Young Roh, Dustin Schones, Keji Zhao During eukaryotic cell differentiation chromatin structure undergoes important changes, as manifested by extensive alterations in histone modifications. It is hypothesized that the profile of these epigenetic markers serves as a signature of the cell identity. To test this, we analyzed high-resolution genomic maps of histone methylations during differentiation of pluripotent hematopoietic stem cells into erythrocyte precursor cells. Our results indicate significant changes in both the dominant patterns of histone modifications and the genes inside the patterns after differentiation. Our results suggest that certain modifications prepare the chromatin for future activation in stem cells and their erasure results in a permanent inactivation of associated genes in differentiation-committed cells. [Preview Abstract] |
Thursday, March 13, 2008 4:54PM - 5:06PM |
W18.00011: Biophysical modeling of transcription initiation by bacterial RNA polymerase Marko Djordjevic RNA polymerase (RNAP) is a central enzyme in cell, which is responsible for gene transcription. As a first step of transcription initiation, RNAP binds to double stranded DNA and opens the two strands of DNA, which is referred to as the open complex formation. We will present the first quantitative model of the open complex formation by bacterial RNAP. The model is based on statistical physics and establishes an explicit relationship between the rate of transcription initiation and physical properties of promoter sequence and promoter-RNAP interactions [1]. The model leads to a very good agreement with the experiments, with no free parameters used in model testing. This agreement strongly supports both the quantitative model that we present and a qualitative mechanism on which the model is based. Bioinformatics applications of the presented work will also be discussed [2]. [1] M Djordjevic and R Bundschuh, under revision in \textit{Biophys. J.}, 2007 [2] M Djordjevic, to be submitted, 2007. [Preview Abstract] |
Thursday, March 13, 2008 5:06PM - 5:18PM |
W18.00012: Nucleosome Positioning and Epigenetics David Schwab, Robijn Bruinsma The role of chromatin structure in gene regulation has recently taken center stage in the field of epigenetics, phenomena that change the phenotype without changing the DNA sequence. Recent work has also shown that nucleosomes, a complex of DNA wrapped around a histone octamer, experience a sequence dependent energy landscape due to the variation in DNA bend stiffness with sequence composition. In this talk, we consider the role nucleosome positioning might play in the formation of heterochromatin, a compact form of DNA generically responsible for gene silencing. In particular, we discuss how different patterns of nucleosome positions, periodic or random, could either facilitate or suppress heterochromatin stability and formation. [Preview Abstract] |
Follow Us |
Engage
Become an APS Member |
My APS
Renew Membership |
Information for |
About APSThe American Physical Society (APS) is a non-profit membership organization working to advance the knowledge of physics. |
© 2024 American Physical Society
| All rights reserved | Terms of Use
| Contact Us
Headquarters
1 Physics Ellipse, College Park, MD 20740-3844
(301) 209-3200
Editorial Office
100 Motor Pkwy, Suite 110, Hauppauge, NY 11788
(631) 591-4000
Office of Public Affairs
529 14th St NW, Suite 1050, Washington, D.C. 20045-2001
(202) 662-8700