Deborah G. Evans

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Name: Evans, Deborah G.

Organization: University of New Mexico , USA

Department: The Nanoscience and Microsystems Program and the Department of Chemistry and Chemical Biology

Title: Professor(PhD)

Chemicals
References

Oligomeric Conjugated Polyelectrolytes Display Site-Preferential Binding to an MS2 Viral Capsid

Co-reporter:Tye D. Martin;Eric H. Hill;David G. Whitten;Eva Y. Chi

Langmuir November 29, 2016 Volume 32(Issue 47) pp:12542-12551

Publication Date(Web):2017-2-22

DOI:10.1021/acs.langmuir.6b01667

Opportunistic bacteria and viruses are a worldwide health threat prompting the need to develop new targeting modalities. A class of novel synthetic poly(phenylene ethynylene) (PPE)-based oligomeric conjugated polyelectrolytes (OPEs) have demonstrated potent wide-spectrum biocidal activity. A subset of cationic OPEs display high antiviral activity against the MS2 bacteriophage. The oligomers have been found to inactivate the bacteriophage and perturb the morphology of the MS2 viral capsid. However, details of the initial binding and interactions between the OPEs and the viruses are not well understood. In this study, we use a multiscale computational approach, including random sampling, molecular dynamics, and electronic structure calculations, to gain an understanding of the molecular-level interactions of a series of OPEs that vary in length, charge, and functional groups with the MS2 capsid. Our results show that OPEs strongly bind to the MS2 capsid protein assembly with binding energies of up to −30 kcal/mol. Free-energy analysis shows that the binding is dominated by strong van der Waals interactions between the hydrophobic OPE backbone and the capsid surface and strong electrostatic free energy contributions between the OPE charged moieties and charged residues on the capsid surface. This knowledge provides molecular-level insight into how to tailor the OPEs to optimize viral capsid disruption and increase OPE efficacy to target amphiphilic protein coats of icosahedral-based viruses.

Computational Study of Bacterial Membrane Disruption by Cationic Biocides: Structural Basis for Water Pore Formation

Co-reporter:Eric H. Hill, David G. Whitten, and Deborah G. Evans

The Journal of Physical Chemistry B 2014 Volume 118(Issue 32) pp:9722-9732

Publication Date(Web):July 11, 2014

DOI:10.1021/jp504297s

The development of biocides as disinfectants that do not induce bacterial resistance is crucial to health care since hospital-acquired infections afflict millions of patients every year. Recent experimental studies of a class of cationic biocides based on the phenylene ethynylene backbone, known as OPEs, have revealed that their biocidal activity is accompanied by strong morphology changes to bacterial cell membranes. In vitro studies of bacterial membrane mimics have shown changes to the lipid phase that are dependent on the length and orientation of the cationic moieties on the backbone. This study uses classical molecular dynamics to conduct a comprehensive survey of how oligomers with different chemical structures interact with each other and with a bacterial cell membrane mimic. In particular, the ability of OPEs to disrupt membrane structure is studied as a function of the length of the biocides and the orientation of their cationic moieties along the backbone of the molecule. The simulation results show that the structure of OPEs radically affects their interactions with a lipid bilayer. Biocides with branched cationic groups form trans-membrane water pores regardless of their backbone length, while only 1–1.5 nm of membrane thinning is observed with biocides with cationic groups on their terminal ends. The molecular dynamics simulations provide mechanistic details at the molecular level of the interaction of these biocidal oligomers and the lipid bilayer and corroborate experimental findings regarding observed differences in membrane disruption by OPEs with different chemical structures.

A Molecular Dynamics and Computational Study of Ligand Docking and Electron Transfer in Ferritins

Co-reporter:Vijaya Subramanian and Deborah G. Evans

The Journal of Physical Chemistry B 2012 Volume 116(Issue 31) pp:9287-9302

Publication Date(Web):June 9, 2012

DOI:10.1021/jp301055x

The mechanism of the reductive release of iron from the cavity of the iron storage protein, ferritin, has been difficult to confirm on the molecular level using experimental studies. In this paper, we use a variety of computational tools to study the binding of flavin redox agents to the protein surface, and the subsequent electron transfer (ET) through the protein coat. Flavin binding sites are identified that represent efficient routes to reduction of Fe(III) across the protein coat in human and bacterial ferritins. Using the pathways model and Dutton’s packing density model, we show that ET across the protein coat to nucleation sites is feasible. Different protein configurations for human heavy and light chain ferritin were obtained along classical molecular dynamics trajectories and used for flavin binding and ET studies. We find that protein configuration affects both the binding and ET rate constants significantly. We show that the maximum possible ET rate constants to the nucleation site GLU-61 in human heavy chain ferritin for protein configurations along a MD simulation trajectory can differ by about 8 orders of magnitude compared to the crystal structure and in human light-chain ferritin rate constants vary by about 4 orders of magnitude.

Synthesis, Self-Assembly, and Photophysical Properties of Cationic Oligo(p-phenyleneethynylene)s

Co-reporter:Yanli Tang, Eric H. Hill, Zhijun Zhou, Deborah G. Evans, Kirk S. Schanze, and David G. Whitten

Langmuir 2011 Volume 27(Issue 8) pp:4945-4955

Publication Date(Web):March 15, 2011

DOI:10.1021/la1050173

Three series of cationic oligo p-phenyleneethynylenes (OPEs) have been synthesized to study their structure−property relationships and gain insights into the transition from molecular to macromolecular properties. The absorbance maxima and molar extinction coefficients in all three sets increase with increasing number of repeat units; however, the increase in λmax between the oligomers having 2 and 3 repeat units is very small, and the oligomer having 3 repeat units shows virtually the same spectra as a p-phenyleneethynylene polymer having 49 repeat units. A computational study of the oligomers using density functional theory calculations indicates that while the simplest oligomers (OPE-1) are fully conjugated, the larger oligomers are nonplanar and the limiting “segment chromophore” may be confined to a near-planar segment extending over three or four phenyl rings. Several of the OPEs self-assemble on anionic “scaffolds”, with pronounced changes in absorption and fluorescence. Both experimental and computational results suggest that the planarization of discrete conjugated segments along the phenylene−ethynylene backbone is predominantly responsible for the photophysical characteristics of the assemblies formed from the larger oligomers. The striking differences in fluorescence between methanol and water are attributed to reversible nucleophilic attack of structured interfacial water on the excited singlet state.

Condensed phase vibrational relaxation: calibration of approximate relaxation theories with analytical and numerically exact results

Co-reporter:Rob D. Coalson, Deborah G. Evans

Chemical Physics 2004 Volume 296(2–3) pp:117-127

Publication Date(Web):26 January 2004

DOI:10.1016/j.chemphys.2003.08.028

Abstract

The dynamics of a small quantum system coupled to condensed phase bath is considered. Such dynamics is important in vibrational and spin relaxation of probe molecules in condensed phase media. Adapting and generalizing the condensed phase electron transfer analysis of Gayen et al. [J. Chem. Phys. 112 (2000) 4310], we show how to compute the reduced system density matrix exactly for a large class of Hamiltonians, namely those for which the system Hamiltonian and the system factor in the system-bath coupling term commute. For this class of problems, several approximate second order relaxation theory equations of motion for the reduced system density matrix also have special properties. In particular, the Markovian limit of these equations of motion forms a positive semigroup. Also, if the bath is a collection of harmonic oscillators, and the bath coupling operator is linear in these oscillator coordinates, then local second order relaxation theory is exact, even for strong system-bath coupling. The case of a degenerate two-level system coupled off-diagonally to the bath is among those that can be solved exactly. In order to treat the nondegenerate two-level analog, we show that the Hamiltonian describing population relaxation of such a system coupled linearly to a harmonic bath can be mapped to the canonical Spin-Boson Hamiltonian, albeit with nonstandard initial state conditions. Nevertheless, Path Integral methods can be utilized to compute numerically exact time-evolution of the equivalent Spin-Boson problem, from which the desired population relaxation dynamics can be extracted. Extensive comparisons to commonly utilized second order relaxation theory approximations are presented.