Structure and Recognition in Microbial Membranes Proteins, and DNA
EMSL Project ID
9593
Abstract
Developments in simulation methodologies as well as computer hardware have enabled the molecular simulation of biological systems of increasing size and with increasing accuracy, providing molecular level detail that is difficult or impossible to obtain experimentally. Computer modeling and simulation studies contribute to our understanding of the behavior of proteins, protein-protein and protein-DNA complexes.In recent years significant progress has been made in applying molecular simulation methods to the study of biological membranes. However, these applications have been focused exclusively on lipid bilayer membranes and on membrane proteins in lipid bilayers. A few simulation studies of outer membrane proteins of Gram-negative bacteria have been reported using simple lipid bilayers, even though this is not a realistic representation of the outer membrane environment. This proposal involves more realistic simulation studies of outer membrane proteins that include the lipopolysaccharide (LPS) layer. This will make simulations much more complex because of several factors: a) the limited experimental data available allowing the construction of a molecular model for a single LPS molecule, b) the need for a parameterization of the oligosaccharide, c) the complicated setup/equilibration procedure as a result of the highly charged LPS molecules that need to be neutralized by counter ions, and d) the increase in computational requirements as a result of the much larger molecular systems. This project will focus on generating a library of outer membrane protein simulations, to provide an opportunity for large scale comparative studies of conformational dynamics within a rather disparate family of membrane proteins. The focus on the bacterial cell wall of Gram-negative bacteria is of direct interest to Department of Energy concerns such as Genomics: GTL, energy production and environmental remediation and restoration.
The second component of the proposed project involves modeling studies of damaged cellular DNA as a result of environmental factors including ionizing radiation. The damage resulting from oxidative stress and ionizing radiation is primarily in the form of oxidized bases, single strand breaks, and loss of bases. The goal of this part of the project is to provide, via large scale computations and simulations, critical information to help characterize the qualitative and quantitative elements that affect structure, stability, and repair characteristics of DNA. This information is important for example in understanding the differences between clustered damage sites in DNA formed by ionizing radiation and singly damaged sites produced by endogenous processes. Changes in base pairing rules can be traced to molecular-level features of the damaged site(s). The premise is that base pairing and base stacking interactions are qualitatively and quantitatively different for singly and multiply damaged DNA sites.
Brian Lower will be using the Bio-AFM to determine that forces of attraction/repulsion between iron oxide minerals and lipopolysaccharide molecules.
Project Details
Project type
Capability Research
Start Date
2005-10-01
End Date
2008-10-05
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Benzene Dimer: High-Level Wave Function and Density Functional Theory Calculations;
M. Pitoˇn´ak, P. Neogr´ady, J. ˇRez´aˇc, P. Jureˇcka, M. Urban and P. Hobza, J. Chem. Theory
Comput. 2008, 4, 1829 - 1834.
Biedermannova L, KE Riley, K Berka, P Hobza, and J Vondrasek. 2008. "Another Role of Proline: Stabilization Interactions in Proteins and Protein Complexes Concerning Proline and Tryptophane." Physical Chemistry Chemical Physics. PCCP 10:6350-6359. doi:10.1039/b805087b
Haranczyk M, and MS Gutowski. 2007. "Differences in Electrostatic Potential Around DNA Fragments Containing Guanine and 8-oxo-Guanine." Theoretical Chemistry Accounts 117(2):291-296.
Haranczyk M, JH Miller, and MS Gutowski. 2007. "Differences in Electrostatic Potential Around DNA Fragments Containing Adenine and 8-oxo-Adenine. An Analysis Based on Regular Cylindrical Projection ." Journal of Molecular Graphics and Modelling 26(1):282-289.
Kannan S, and M Zacharias. 2006. "Enhanced Sampling of Peptide and Protein Conformations Using Replica Exchange Simulations With a Peptide Backbone Biasing-Potential." Proteins. Structure, Function, and Bioinformatics 66:697-706.
Kannan S, and M Zacharias. 2007. "Folding of a DNA Hairpin Loop Structure in Explicit Solvent Using Replica-Exchange Molecular Dynamics Simulations." Biophysical Journal 93:3218-3228.
Kannan S, K Kohloff, and M Zacharias. 2006. "B-DNA Under Stress: Over- and Untwisting of DNA during Molecular Dynamics Simulations." Biophysical Journal 91(8):2956-2965. doi:10.1529/biophysj.106.087163
Kara M, and MW Zacharias. 2013. "Influence of 8-Oxoguanosine on the Fine Structure of DNA Studied with Biasing-Potential Replica Exchange Simulations." Biophysical Journal 104(5):1089-1097. doi:10.1016/j.bpj.2013.01.032
Lins RD, ER Vorpagel, M Guglielmi, and TP Straatsma. 2008. "Computer Simulation of Uranyl Uptake by the Rough Lipopolysaccharide Membrane of Pseudomonas aeruginosa." Biomacromolecules 9(1):29-35. doi:10.1021/bm700609
Li X, KH Bowen, M Haranczyk, RA Bachorz, K Mazurkiewicz, J Rak, and MS Gutowski. 2007. "Photoelectron Spectroscopy of Adiabatically Bound Valence Anions of Rare Tautomers of the Nucleic Acid Bases." Journal of Chemical Physics 127(17):Art. 174309. doi:10.1063/1.2795719
Lower BH, RD Lins, ZW Oestreicher, TP Straatsma, MF Hochella Jr., L Shi, and SK Lower. 2008. "In Vitro Evolution of a Peptide with a Hematite Binding Motif That May Constitute a Natural Metal-Oxide Binding Archetype ." Environmental Science & Technology 42(10):3821-3827. doi:10.1021/es702688c
Mazurkiewicz K, M Haranczyk, MS Gutowski, and J Rak. 2007. "Can an excess electron localise on a purine moiety in the adenine-thymine Watson-Crick base pair? A computational study." International Journal of Quantum Chemistry 107(12):2224-2232.
Pitonak M, KE Riley, P Neogrady, and P Hobza. 2008. "Highly Accurate CCSD(T) and DFT–SAPT Stabilization Energies of H-Bonded and Stacked Structures of the Uracil Dimer." Chemphyschem 9:1636-1644. doi:10.1002/cphc.200800286
Rezac J, and P Hobza. 2008. "Benzene Dimer: Dynamic Structure and Thermodynamics Derived from On-the-Fly ab initio DFT-D Molecular Dynamic Simulations." Journal of Chemical Theory and Computation 4(11):1835-1840. doi:10.1021/ct8002282
Riley KE, and P Hobza. 2008. "Investigations into the Nature of Halogen Bonding Including Symmetry Adapted Perturbation Theory Analyses." Journal of Chemical Theory and Computation 4:232-242. doi:10.1021/ct700216w
Roccatano D, A Barthel, and M Zacharias. 2007. "Structural Flexibility of the Nucleosome Core Particle at Atomic Resolution studied by Molecular Dynamics Simulation." Biopolymers 85(5):407-421.
Sieker F, S Springer, and M Zacharias. 2007. "Comparative molecular dynamics analysis of tapasin-dependent and -independent MHC class I alleles." Protein Science 16(2):299-308.
Sponer J, KE Riley, and P Hobza. 2008. "Nature and Magnitude of Aromatic Stacking of Nucleic Acid Bases." Physical Chemistry Chemical Physics. PCCP 10:2595-2610. doi:10.1039/b719370j
Stopka S A,Agtuca B J,Koppenaal D W,Pasa Tolic L ,Stacey G ,Vertes A ,Anderton C R 2016. "Laser Ablation Electrospray Ionization Mass Spectrometry with Ion Mobility Separation Reveals Metabolites and Lipids in the Symbiotic Interactions of Soybean Roots and Rhizobia" Plant Physiology
Valdes H, K Pluhackova, M Pitonak, J Rezac, and P Hobza. 2008. "Benchmark Database on Isolated Small Peptides Containing an Aromatic Side Chain: Comparison Between Wave Function and Density Functional Theory Methods and Empirical Force Field." Physical Chemistry Chemical Physics. PCCP 10:2747-2757. doi:10.1039/b719294k
Valdes H, V Spiwok, J Rezac, D Reha, AG Abo-Riziq, MS de Vries, and P Hobza. 2008. "Potential-Energy and Free-Energy Surfaces of Glycyl-Phenylalanyl-Alanine (GFA) Tripeptide: Experiment and Theory." Chemistry - a European Journal 14:4886-4898. doi:10.1002/chem.200800085
Velickovic D.S., B.J. Agtuca, S.A. Stopka, A. Vertes, D.W. Koppenaal, L. Pasa Tolic, and G. Stacey, et al. 2018. "Observed Metabolic Asymmetry Within Soybean Root Nodules Reflects Unexpected Complexity in Rhizobacteria-legume Metabolite Exchange." Nature. PNNL-SA-127419. doi:10.1038/s41396-018-0188-8
Yongsunthon R, V Fowler, BH Lower, FP Vellano, E Alexander, L Reller, G Corey, and SK Lower. 2007. "Correlation between fundamental binding forces and clinical prognosis of Staphylococcus aureus infections of medical implants." Langmuir 23:2289-2292.
Zacharias M. 2006. "Minor Groove Deformability of DNA: A Molecular Dynamics Free Energy Simulation Study." Biophysical Journal 91(3):882-891. doi:10.1529/biophysj.106.083816