EMSL: Erich Vorpagel's Publications

Yang Z, ER Vorpagel, and J Laskin. 2009. "Influence of the Charge State on the Structures and Interactions of Vancomycin Antibiotics with Cell-Wall Analogue Peptides: Experimental and Theoretical Studies." Chemistry - a European Journal 15(9):2081-2090. doi:10.1002/chem.200802010 Abstract In this study we examined the effect of the charge state on the energetics and dynamics of dissociation of the non-covalent complex between the vancomycin and the cell wall peptide analogue Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala (V-Ac2KDADA). The binding energies between the vancomycin and the peptide were obtained from the RRKM modeling of the time- and energy resolved surface-induced dissociation (SID) experiments. Our results demonstrate that the stability of the complex toward fragmentation increases in the order: [V+Ac2KDADA+H]+2 < [V+Ac2KDADA+H]+ < [V+Ac2KDADA-H]-. Dissociation of the singly protonated and singly deprotonated complex is characterized by very large entropy effects indicating substantial increase in the conformational flexibility of the resulting products. The experimental threshold energies of 1.75 eV and 1.34 eV obtained for the [V+Ac2KDADA-H]- and [V+Ac2KDADA+H]+ , respectively, are in excellent agreement with the results of density functional theory (DFT) calculations. The increased stability of the deprotonated complex observed experimentally is attributed to the presence of three charged sites in the deprotonated complex as compared to only one charged site in the singly protonated complex. The low binding energy of 0.93 eV obtained for the doubly protonated complex suggests that this ion is destabilized by Coulomb repulsion between the singly protonated vancomycin and the singly protonated peptide comprising the complex.

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/bm700609r Abstract Heavy metal environmental contaminants cannot be destroyed but require containment, preferably in concentrated form, in a solid or immobile form for recycling or final disposal. Microorganisms are able to take up and deposit high levels of contaminant metals, including radioactive metals such as uranium and plutonium, into their cell wall. Consequently, these microbial systems are of great interest as the basis for potential environmental bioremediation technologies. The outer membranes of Gram-negative microbes are highly non-symmetric and exhibit a significant electrostatic potential gradient across the membrane. This gradient has a significant effect on the uptake and transport of charged and dipolar compounds. However, the effectiveness of microbial systems for environmental remediation will depend strongly on specific properties that determine the uptake of targeted contaminants by a particular cell wall. To aid in the design of microbial remediation technologies, knowledge of the factors that determine the affinity of a particular bacterial outer membrane for the most common ionic species found in contaminated soils and groundwater is of great importance. Using our previously developed model for the lipopolisaccharide (LPS) membrane of Pseudomonas aeruginosa, this work presents the potentials of mean force as the estimate of the free energy profile for uptake of sodium, calcium, chloride, uranyl ions and a water molecule by the bacterial LPS membrane. A compatible classical parameter set for uranyl has been developed and validated. Results show that the uptake of uranyl is energetically a favorable process relative to the other ions studied. At neutral pH, this nuclide is shown to be retained on the surface of the LPS membrane through chelation with the carboxyl and hydroxyl groups located in the outer-core.

Yang Z, ER Vorpagel, and J Laskin. 2008. "Experimental and Theoretical Studies of the Structures and Interactions of Vancomycin Antibiotics with Cell Wall Analogues." Journal of the American Chemical Society 130(39):13013-13022. doi:10.1021/ja802643g Abstract Surface-induced dissociation (SID) of the singly protonated complex of vancomycin antibiotic with cell wall peptide analogue (Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala) was studied using a 6 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS) specially configured for SID experiments. The binding energy between the vancomycin and the peptide was obtained from the RRKM modeling of the time- and energy resolved fragmentation efficiency curves (TFECs) of the precursor ion and its fragments. Electronic structure calculations of the geometries, proton affinities and binding energies were performed for several model systems including vancomycin (V), vancomycin aglycon (VA), Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala, and non-covalent complexes of VA with N-acetyl-D-Ala-D-Ala and Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala at the B3LYP/6-31G(d) level of theory. Comparison between the experimental and computational results suggests that the most probable structure of the complex observed in our experiments corresponds to the neutral peptide bound to the vancomycin protonated at the secondary amino group of the N-methyl-leucine residue. The experimental binding energy of 30.9 ± 1.8 kcal/mol is in good agreement with the binding energy of 29.3 ± 2.5 kcal/mol calculated for the model system representing the preferred structure of the complex.

Herrmann KA, VH Wysocki, and ER Vorpagel. 2005. "Computational Investigation and Hydrogen/Deuterium Exchange of the Fixed Charge Derivative Tris(2,4,6-Trimethoxyphenyl)Phosphonium: Implications for the Aspartic Acid Cleavage Mechanism." Journal of the American Society for Mass Spectrometry 16(7):1067-1080. Abstract Aspartic acid (Asp)-containing peptides with the fixed charge derivative tris(2,4,6-trimethoxyphenyl) phosphonium (tTMP-P+) were explored computationally and experimentally by H/D exchange and fragmentation studies in order to probe the phenomenon of selective cleavage C-terminal to Asp in the absence of a "mobile" proton. Ab initio modeling of the tTMP-P+ electrostatic potential demonstrates the positive charge is distributed on the phosphonium group and therefore is not initiating or directing fragmentation as would a "mobile" proton. Geometry optimizations and vibrational analyses of different aspartic acid conformations show the aspartic acid structure with a hydrogen bond between the side chain hydroxy and backbone carbonyl lies 2.8 kcal/mol above the lowest energy conformer. In reactions with D2O, the phosphonium-derived doubly charged peptide (H+)P+LDIFSDF rapidly exchanges all 12 of its exchangeable hydrogens for deuterium and also displays a non-exchanging population. With no added proton, P+LDIFSDF exchanges a maximum of four of eleven exchangeable hydrogens for deuterium. No exchange is observed when all acidic groups are converted to the corresponding methyl esters. Together, these H/D exchange results indicate that the acidic hydrogens are "mobile locally" because they are able to participate in exchange even in the absence of an added proton. Fragmentation of two distinct (H+)P+LDIFSDF ion populations shows the non-exchanging population displays selective cleavage, while the exchanging population fragments more evenly across the peptide backbone. This result demonstrates that H/D exchange can sometimes distinguish between and provide a means of separation of different protonation motifs, and that these protonation motifs can have an effect on the fragmentation.

Lin Y, SK Fiskum, W Yantasee, H Wu, SV Mattigod, ER Vorpagel, GE Fryxell, KN Raymond, and J Xu. 2005. "Incorporation of Hydroxypyridinone (HOPO) Ligands into Self-Assembled Monolayers on Mesoporous Supports for Selective Actinide Sequestration." Environmental Science and Technology 39(5):1332-1337. doi:10.1021/es049169t Abstract In this study, three isomers of hydroxypyridinones, 1,2-HOPO, 3,2-HOPO, and 3,4-HOPO, were attached to self-assembled monolayers on mesoporous silica. (SAMMS). The HOPO-SAMMS materials have superior solid adsorbents properties: they do not suffer from solvent swelling, their rigid, open pore structure allow rapid sorption kinetics, their extremely high surface area enables the installation of high functional density, and being silica-based they are compatible with vitrification into a final glasseous waste form. Kinetics, equilibrium, and selectivity of the adsorptions of actinide on the HOPO-SAMMS at various pHs, and in the presences of other metal cations, anions and competing ligands are reported. Rapid sequestration of U (VI), Np (V) and Pu (IV) was observed. Very little competition from transition metal cations and common species was observed.

Tan X, P Nalbant, A Toutchkine, D Hu, ER Vorpagel, KM Hahn, and HP Lu. 2004. "Single-Molecule Study of Protein-Protein Interaction Dynamics in a Cell Signaling System." Journal of Physical Chemistry B 108(2):737-744. Abstract We report a combined single-molecule fluorescence and molecular dynamics (MD) simulation study of protein-protein interactions in a GTP-binding intracellular signaling protein Cdc42 in complex with a downstream effector protein WASP. A 13- kDa WASP fragment which binds only the activated GTP-loaded Cdc42 was labeled with a novel solvatochromic dye and used to probe hydrophobic interactions significant to Cdc42/WASP recognition. Our single-molecule fluorescence measurements have shown conformational fluctuations of the protein complex and suggested multiple conformational states at a wide range of time scales might be involved in protein interaction dynamics. Single-molecule experiments have revealed the dynamic disorder or protein-protein interactions within the Cdc42/WASP complex, which may be important for regulating downstream signaling events.

Yang X, XB Wang, ER Vorpagel, and LS Wang. 2004. "Direct Experimental Observation of the Low Ionization Potentials of Guanine in Free Oligonucleotides by Using Photoelectron Spectroscopy." Proceedings of the National Academy of Sciences of the United States of America 101(51):17588-17592. Abstract Photodetachment photoelectron spectroscopy is used to probe the electronic structure of mono-, di-, and trinucleotide anions in the gas phase. A weak and well defined threshold band was observed in the photoelectron spectrum of 2' -deoxyguanosine 5' -mono-phosphate at a much lower ionizztion energy than the other three mononucleotides. Density function theory calculations revealed that this unique spectral feature is caused by electron-detachment from a п orbital of the guanine base on 2’ –deoxyguanosine 5’ –monop0hosphate, whereas the lowest ionization channel for the other three mononucleotides takes place from the phosphate group. This low-energy feature was shown to be a “fingerprint” in all the spectra of dinucleotides and trinucleotides that contain the guanine base. The current experiment provides direct spectroscopic evidence that the guanine base is the site with the lowest ionization potential in oligonucleotides and DNA and is consistent with the fact that guanine is most susceptible to oxidation to give the guanine cation in DNA damage.

Chen Y, D Hu, ER Vorpagel, and HP Lu. 2003. "Probing Single-Molecule T4 Lysozyme Conformational Dynamics by Intramolecular Fluorescence Energy Transfer." Journal of Physical Chemistry B 107:7947-7956. Abstract We demonstrate the use of single-molecule spectroscopy to study enzyme conformational motions of T4 lysozyme under hydrolysis reaction of the polysaccharide walls of E. Coli B cells.By attaching a donoracceptor pair of dye molecules site-specifically to noninterfering sites on the enzyme, the hinge-bending motions of the enzyme are measured by monitoring the donor-acceptor emission intensity as a function of time. The overall enzymatic reaction rate constants are found to vary widely from molecule to molecule. The dominant contribution to this static inhomogeneity is attributed to enzyme searching for reactive sites on the substrate.

Smith DMA, M Dupuis, ER Vorpagel, and TP Straatsma. 2003. "Characterization of Electronic Structure and Properties of a bis(histidine) Heme Model Complex." Journal of the American Chemical Society 125(9):2711-2717. Abstract Ferric and ferrous hemes, such as those present in electron transfer proteins, often have low-lying spin states that are very close in energy. In order to explore the relationship between spin state, geometry and cytochrome electron transfer, we investigate, using density functional theory, the relative energies, electronic structure, and optimized geometries for a high- and low- spin ferric and ferrous heme model complex. Our model complex consists of an iron-porphyrin axially ligated by two imidazoles, which model the attachment of the hemes to cytochrome histidines. Using the B3LYP hybrid functional, we found that, in the ferric model heme complex, the doublet is lower in energy than the sextet by 8.60 kcal/mol, and the singlet ferrous heme is 7.60 kcal/mol more stable than the quintet. The difference between the high-spin ferric and ferrous model heme energies yields an adiabatic electron affinity (AEA) of 5.21 eV, and the low-spin AEA is 5.17 eV. Both values are large enough to ensure electron trapping, and electronic structure analysis indicates that the dxy orbital is most likely involved in the electron transfer between neighboring hemes (the xy-plane is the plane of the porphyrin). The B3LYP electronic structure was verified by the calculated Mossbauer parameters, which are consistent with experimental values, and isotropic hyperfine coupling constants were evaluated for the ligand nitrogen atoms in each of the hemes. The optimized geometries of the ferric and ferrous hemes are consistent with structures from X-ray crystallography and reveal that the iron-imidazole distances are significantly longer in the high- spin model hemes, which suggests that the protein environment, modeled here by the imidazoles, plays an important role in regulating the spin state.

Mccurdy PR, ER Vorpagel, and WP Hess. 2001. "Ultraviolet Photochemistry of Hydrogen-Bonded HBr-Acetone Complexes in Argon Matrices." Journal of Chemical Physics 114(1):169-178. Abstract We have studied the effects of UV radiation on HBr-acetone Ar Matrices. Results indicate photoproducts formed from the irradiation of these matrices depend on the wavelength of light used. Irradiation at 266 and 309 nm results only in the loss of the H-bonded HBr-acetone complex and the photo-production of an HBr-1-propen-2-ol complex. Ab initio calculations of HBr-1-propen-2-ol complexes support this finding. Irradiation at 193 nm shows a high degree of fragmentation of all molecules as indicated by CH4, CO, and CO2 product peaks in the infrared spectrum and the loss of all peaks associated with HBr, acetone and their complex. In contrast, irradiation at 355 nm shows no change in the infrared spectra even after prolonged irradiation. For 266 and 309 nm light, a minor photoreaction channel to a non-H-bonded HBr-acetone complex is also noted.