Irene Newhouse - Academia.edu (original) (raw)

Papers by Irene Newhouse

Research paper thumbnail of Barrier Discharge Optimization for Nitric Oxide Destruction

Journal of Advanced Oxidation Technologies

Concern over smog and acid rain has created a need for innovative technologies that destroy or re... more Concern over smog and acid rain has created a need for innovative technologies that destroy or remove nitric oxide (NO) from many gas streams. One promising technology is the Non-Thermal Plasma Discharge (NTPD). Although NTPDs have been used to oxidize and reduce NO, previous studies found that these devices required a non-competitive amount of electrical energy input, preventing their wide-spread application. In this paper, we report on our experimental investigation into techniques to increase the efficiency of NTPDs. Specifically, two approaches were investigated. The first approach considered was the upstream injection of chemical additives. It is known that certain additives increase the chemical efficiency of desired reactions, thus reducing the required electrical energy. Several additives were tested, and their effect is summarized in this paper. It was found that upstream injection of ethanol in a diesel exhaust stream reduced the energy requirement from more than 150 elect...

Research paper thumbnail of Computations of Vibrational Infrared Frequencies of Selected Amines

Research paper thumbnail of Fractal-like energy transport and fusion in a naphthalene-doped polymeric glass*1

Journal of Luminescence, Dec 1, 1984

Singlet energy transport in naphthalene-doped poly(methylmethacrylate) (PMMA( samples has been fo... more Singlet energy transport in naphthalene-doped poly(methylmethacrylate) (PMMA( samples has been found, by doping with anthracene, to follow Stern-Volmer kinetics with a transfer rate constant ca. 2x10 9. Delayed fluorescence is easily observed; triplet energy transport seems to have fractal-like properties.

Research paper thumbnail of Exciton Transport in Naphthalene-Doped Poly (Methylmethyl-Acrylate): Spatial and Energetic Disorder

Unconventional Photoactive Solids, 1988

Research paper thumbnail of Allosteric pocket of the dengue virus (serotype 2) NS2B/NS3 protease: In silico ligand screening and molecular dynamics studies of inhibition

Journal of molecular graphics & modelling, 2014

The allosteric pocket of the Dengue virus (DENV2) NS2B/NS3 protease, which is proximal to its cat... more The allosteric pocket of the Dengue virus (DENV2) NS2B/NS3 protease, which is proximal to its catalytic triad, represents a promising drug target (Othman et al., 2008). We have explored this binding site through large-scale virtual screening and molecular dynamics simulations followed by calculations of binding free energy. We propose two mechanisms for enzyme inhibition. A ligand may either destabilize electronic density or create steric effects relating to the catalytic triad residues NS3-HIS51, NS3-ASP75, and NS3-SER135. A ligand may also disrupt movement of the C-terminal of NS2B required for inter-conversion between the "open" and "closed" conformations. We found that chalcone and adenosine derivatives had the top potential for drug discovery hits, acting through both inhibitory mechanisms. Studying the molecular mechanisms of these compounds might be helpful in further investigations of the allosteric pocket and its potential for drug discovery.

Research paper thumbnail of nuclear-chicago CORPORATION

Research paper thumbnail of The oxidative degradation of imide polymers. I: Ozonolysis of a model compound, N-phenylphthalimide

Polymer Engineering and Science, 1994

ABSTRACT The reactions of N-phenylphthalimide films with ozone have been studied under a variety ... more ABSTRACT The reactions of N-phenylphthalimide films with ozone have been studied under a variety of conditions: dry ozone, moist ozone, ozone plus ultraviolet light, as well as ozone plus water vapor plus ultraviolet light. This compound is a conveniently available model for imide polymers. These reaction conditions represent simulation of certain aspects of the space environment. For each set of reaction conditions the reaction products were determined by combined gas chromatography/mass spectrometry. Semiempirical molecular orbital computations were made of the relative energetics of possible reaction pathways consistent with the generation of the observed products. The reaction products found indicate fragmentation of the imidic moiety for which the energetics are favorable.

Research paper thumbnail of Molecular dynamics study of hell’s gate globin I (HGbI) from a methanotrophic extremophile: oxygen migration through a large cavity

Journal of Molecular Modeling, 2013

Hell's gate globin I (HGbI), a heme-containing pr... more Hell's gate globin I (HGbI), a heme-containing protein from the extremophile Methylacidiphilum infernorum, has fast oxygen-binding/slow release characteristics due to its distal residues Gln and Tyr. The combination of Gln/Tyr distal iron coordination, adaptation to extreme environmental conditions, and lack of a D helix suggests that ligand migration in HGbI differs from other previously studied globins. Locally enhanced molecular dynamics trajectories of oxygen migration indicate a large internal cavity. This may increase the tendency of oxygen to exit from portals other than the most direct exit from the space near the heme. Oxygen may reside transiently in shallow surface depressions around the exits. Such surface trapping may enhance both oxygen uptake by increasing contact time between molecules, and decrease release by increasing the probability of oxygen reentry from the vicinity of the portal.

Research paper thumbnail of Distinct Glycan Topology for Avian and Human Sialopentasaccharide Receptor Analogues upon Binding Different Hemagglutinins: A Molecular Dynamics Perspective

Journal of Molecular Biology, 2009

Hemagglutinin (HA) binds to sialylated glycans exposed on the host cell surface in the initial st... more Hemagglutinin (HA) binds to sialylated glycans exposed on the host cell surface in the initial stage of avian influenza virus infection. It has been previously hypothesized that glycan topology plays a critical role in the human adaptation of avian flu viruses, such as the potentially pandemic H5N1. Comparative molecular dynamics (MD) studies are complementary to experimental techniques including glycan microarray to understand better the mechanism of species specificity switch. The examined systems comprise explicitly solvated trimeric forms of avian H3, H5, and swine H9 in complex with avian and human glycan receptor analogs, α-2,3 linked lactoseries tetrasaccharide a (LSTa) and α-2,6 linked LSTc, respectively. The glycans adopted distinct topological profiles with inducible torsional angles when bound to different HA's. The corresponding receptor binding domain amino acid contact profiles were also distinct. Avian H5 was able to accommodate LSTc in a tightly "folded-umbrella"-like topology through interactions with all five sugar residues. After considering conformational entropy, the relative binding free energy changes, calculated using the molecular mechanics-generalized Born surface area (MM-GBSA) technique, were in agreement with previous experimental findings, and also provided insights on electrostatic, van der Waals, desolvation and entropic contributions to HA-glycan interactions. The topology profile and the relative abundance of free glycan receptors may influence receptor binding kinetics. Glycan composition and topological changes upon binding different HA may be important determinants in species specificity switch. GBTotal is the total binding free energy before entropic connection;ΔS RTV is the rotational, translational and vibrational entropy calculated from normal mode analysis; ΔS Conf is the conformational entropic penalty calculated from quasi-harmonic analysis of the glycosidic internal rotations.

Research paper thumbnail of Fractal-like energy transport and fusion in a naphthalene-doped polymeric glass

Journal of Luminescence, 1984

Singlet energy transport in naphthalene-doped poly(methylmethacrylate) (PMMA( samples has been fo... more Singlet energy transport in naphthalene-doped poly(methylmethacrylate) (PMMA( samples has been found, by doping with anthracene, to follow Stern-Volmer kinetics with a transfer rate constant ca. 2x10 9. Delayed fluorescence is easily observed; triplet energy transport seems to have fractal-like properties.

Research paper thumbnail of Docking of Noncompetitive Inhibitors into Dengue Virus Type 2 Protease: Understanding the Interactions with Allosteric Binding Sites

Journal of Chemical Information and Modeling, 2008

A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously... more A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously reported to show varying degrees of noncompetitive inhibitory activities toward Dengue virus type 2 (Den2) protease. Results obtained from automated docking studies are in agreement with experimental data in which the ligands were shown to bind to sites other than the active site of the protease. The calculated K(i) values are very small, indicating that the ligands bind quite well to the allosteric binding site. Greater inhibition by pinostrobin, compared to the other compounds, can be explained by H-bonding interaction with the backbone carbonyl of Lys74, which is bonded to Asp75 (one of the catalytic triad residues). In addition, structure-activity relationship analysis yields structural information that may be useful for designing more effective therapeutic drugs against dengue virus infections.

Research paper thumbnail of Fractal-like triplet-triplet annihilation kinetics in naphthalene-doped poly(methylmethacrylate)

Chemical Physics Letters, 1988

ABSTRACT

Research paper thumbnail of An AM1 SCF MO study of the reaction of formaldehyde with atomic oxygen

Chemical Physics Letters, 1989

ABSTRACT The decomposition process for formaldehyde in the presence of atomic oxygen has been inv... more ABSTRACT The decomposition process for formaldehyde in the presence of atomic oxygen has been investigated using AM1 semiempirical SCF MO calculations. It is found that for both singlet and triplet energy surfaces the most facile predicted decomposition pathway involves insertion of atomic oxygen to form formic acid followed by a second insertion to produce carbonic acid which then decomposed to CO2 and H2O. Decomposition through a tetrahedral H2CO2 methylenebis(oxy) species, considered by some previous workers, is predicted to be an unfavorable process.

Research paper thumbnail of Mechanism of Glycan Receptor Recognition and Specificity Switch for Avian, Swine and Human Adapted Influenza Virus Hemagglutinins: A Molecular Dynamics Perspective

Biophysical Journal, 2010

Hemagglutinins (HA's) from duck, swine, and human influenza viruses have previously been shown to... more Hemagglutinins (HA's) from duck, swine, and human influenza viruses have previously been shown to prefer avian and human glycan receptor analogues with distinct topological profiles, pentasaccharides LSTa (R-2,3 linkage) and LSTc (R-2,6 linkage), in comparative molecular dynamics studies. On the basis of detailed analyses of the dynamic motions of the receptor binding domains (RBDs) and interaction energy profiles with individual glycan residues, we have identified ∼30 residue positions in the RBD that present distinct profiles with the receptor analogues. Glycan binding constrained the conformational space sampling by the HA. Electrostatic steering appeared to play a key role in glycan binding specificity. The complex dynamic behaviors of the major SSE and trimeric interfaces with or without bound glycans suggested that networks of interactions might account for species specificity in these low affinity and high avidity (multivalent) interactions between different HA and glycans. Contact frequency, energetic decomposition, and H-bond analyses revealed species-specific differences in HA-glycan interaction profiles, not readily discernible from crystal structures alone. Interaction energy profiles indicated that mutation events at the set of residues such as 145, 156, 158, and 222 would favor human or avian receptor analogues, often through interactions with distal asialo-residues. These results correlate well with existing experimental evidence, and suggest new opportunities for simulation-based vaccine and drug development.

Research paper thumbnail of Docking of Noncompetitive Inhibitors into Dengue Virus Type 2 Protease: Understanding the Interactions with Allosteric Binding Sites

Journal of Chemical Information and Modeling, 2008

A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously... more A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously reported to show varying degrees of noncompetitive inhibitory activities toward Dengue virus type 2 (Den2) protease. Results obtained from automated docking studies are in agreement with experimental data in which the ligands were shown to bind to sites other than the active site of the protease. The calculated K(i) values are very small, indicating that the ligands bind quite well to the allosteric binding site. Greater inhibition by pinostrobin, compared to the other compounds, can be explained by H-bonding interaction with the backbone carbonyl of Lys74, which is bonded to Asp75 (one of the catalytic triad residues). In addition, structure-activity relationship analysis yields structural information that may be useful for designing more effective therapeutic drugs against dengue virus infections.

Research paper thumbnail of Barrier Discharge Optimization for Nitric Oxide Destruction

Journal of Advanced Oxidation Technologies

Concern over smog and acid rain has created a need for innovative technologies that destroy or re... more Concern over smog and acid rain has created a need for innovative technologies that destroy or remove nitric oxide (NO) from many gas streams. One promising technology is the Non-Thermal Plasma Discharge (NTPD). Although NTPDs have been used to oxidize and reduce NO, previous studies found that these devices required a non-competitive amount of electrical energy input, preventing their wide-spread application. In this paper, we report on our experimental investigation into techniques to increase the efficiency of NTPDs. Specifically, two approaches were investigated. The first approach considered was the upstream injection of chemical additives. It is known that certain additives increase the chemical efficiency of desired reactions, thus reducing the required electrical energy. Several additives were tested, and their effect is summarized in this paper. It was found that upstream injection of ethanol in a diesel exhaust stream reduced the energy requirement from more than 150 elect...

Research paper thumbnail of Computations of Vibrational Infrared Frequencies of Selected Amines

Research paper thumbnail of Fractal-like energy transport and fusion in a naphthalene-doped polymeric glass*1

Journal of Luminescence, Dec 1, 1984

Singlet energy transport in naphthalene-doped poly(methylmethacrylate) (PMMA( samples has been fo... more Singlet energy transport in naphthalene-doped poly(methylmethacrylate) (PMMA( samples has been found, by doping with anthracene, to follow Stern-Volmer kinetics with a transfer rate constant ca. 2x10 9. Delayed fluorescence is easily observed; triplet energy transport seems to have fractal-like properties.

Research paper thumbnail of Exciton Transport in Naphthalene-Doped Poly (Methylmethyl-Acrylate): Spatial and Energetic Disorder

Unconventional Photoactive Solids, 1988

Research paper thumbnail of Allosteric pocket of the dengue virus (serotype 2) NS2B/NS3 protease: In silico ligand screening and molecular dynamics studies of inhibition

Journal of molecular graphics & modelling, 2014

The allosteric pocket of the Dengue virus (DENV2) NS2B/NS3 protease, which is proximal to its cat... more The allosteric pocket of the Dengue virus (DENV2) NS2B/NS3 protease, which is proximal to its catalytic triad, represents a promising drug target (Othman et al., 2008). We have explored this binding site through large-scale virtual screening and molecular dynamics simulations followed by calculations of binding free energy. We propose two mechanisms for enzyme inhibition. A ligand may either destabilize electronic density or create steric effects relating to the catalytic triad residues NS3-HIS51, NS3-ASP75, and NS3-SER135. A ligand may also disrupt movement of the C-terminal of NS2B required for inter-conversion between the "open" and "closed" conformations. We found that chalcone and adenosine derivatives had the top potential for drug discovery hits, acting through both inhibitory mechanisms. Studying the molecular mechanisms of these compounds might be helpful in further investigations of the allosteric pocket and its potential for drug discovery.

Research paper thumbnail of nuclear-chicago CORPORATION

Research paper thumbnail of The oxidative degradation of imide polymers. I: Ozonolysis of a model compound, N-phenylphthalimide

Polymer Engineering and Science, 1994

ABSTRACT The reactions of N-phenylphthalimide films with ozone have been studied under a variety ... more ABSTRACT The reactions of N-phenylphthalimide films with ozone have been studied under a variety of conditions: dry ozone, moist ozone, ozone plus ultraviolet light, as well as ozone plus water vapor plus ultraviolet light. This compound is a conveniently available model for imide polymers. These reaction conditions represent simulation of certain aspects of the space environment. For each set of reaction conditions the reaction products were determined by combined gas chromatography/mass spectrometry. Semiempirical molecular orbital computations were made of the relative energetics of possible reaction pathways consistent with the generation of the observed products. The reaction products found indicate fragmentation of the imidic moiety for which the energetics are favorable.

Research paper thumbnail of Molecular dynamics study of hell’s gate globin I (HGbI) from a methanotrophic extremophile: oxygen migration through a large cavity

Journal of Molecular Modeling, 2013

Hell's gate globin I (HGbI), a heme-containing pr... more Hell's gate globin I (HGbI), a heme-containing protein from the extremophile Methylacidiphilum infernorum, has fast oxygen-binding/slow release characteristics due to its distal residues Gln and Tyr. The combination of Gln/Tyr distal iron coordination, adaptation to extreme environmental conditions, and lack of a D helix suggests that ligand migration in HGbI differs from other previously studied globins. Locally enhanced molecular dynamics trajectories of oxygen migration indicate a large internal cavity. This may increase the tendency of oxygen to exit from portals other than the most direct exit from the space near the heme. Oxygen may reside transiently in shallow surface depressions around the exits. Such surface trapping may enhance both oxygen uptake by increasing contact time between molecules, and decrease release by increasing the probability of oxygen reentry from the vicinity of the portal.

Research paper thumbnail of Distinct Glycan Topology for Avian and Human Sialopentasaccharide Receptor Analogues upon Binding Different Hemagglutinins: A Molecular Dynamics Perspective

Journal of Molecular Biology, 2009

Hemagglutinin (HA) binds to sialylated glycans exposed on the host cell surface in the initial st... more Hemagglutinin (HA) binds to sialylated glycans exposed on the host cell surface in the initial stage of avian influenza virus infection. It has been previously hypothesized that glycan topology plays a critical role in the human adaptation of avian flu viruses, such as the potentially pandemic H5N1. Comparative molecular dynamics (MD) studies are complementary to experimental techniques including glycan microarray to understand better the mechanism of species specificity switch. The examined systems comprise explicitly solvated trimeric forms of avian H3, H5, and swine H9 in complex with avian and human glycan receptor analogs, α-2,3 linked lactoseries tetrasaccharide a (LSTa) and α-2,6 linked LSTc, respectively. The glycans adopted distinct topological profiles with inducible torsional angles when bound to different HA's. The corresponding receptor binding domain amino acid contact profiles were also distinct. Avian H5 was able to accommodate LSTc in a tightly "folded-umbrella"-like topology through interactions with all five sugar residues. After considering conformational entropy, the relative binding free energy changes, calculated using the molecular mechanics-generalized Born surface area (MM-GBSA) technique, were in agreement with previous experimental findings, and also provided insights on electrostatic, van der Waals, desolvation and entropic contributions to HA-glycan interactions. The topology profile and the relative abundance of free glycan receptors may influence receptor binding kinetics. Glycan composition and topological changes upon binding different HA may be important determinants in species specificity switch. GBTotal is the total binding free energy before entropic connection;ΔS RTV is the rotational, translational and vibrational entropy calculated from normal mode analysis; ΔS Conf is the conformational entropic penalty calculated from quasi-harmonic analysis of the glycosidic internal rotations.

Research paper thumbnail of Fractal-like energy transport and fusion in a naphthalene-doped polymeric glass

Journal of Luminescence, 1984

Singlet energy transport in naphthalene-doped poly(methylmethacrylate) (PMMA( samples has been fo... more Singlet energy transport in naphthalene-doped poly(methylmethacrylate) (PMMA( samples has been found, by doping with anthracene, to follow Stern-Volmer kinetics with a transfer rate constant ca. 2x10 9. Delayed fluorescence is easily observed; triplet energy transport seems to have fractal-like properties.

Research paper thumbnail of Docking of Noncompetitive Inhibitors into Dengue Virus Type 2 Protease: Understanding the Interactions with Allosteric Binding Sites

Journal of Chemical Information and Modeling, 2008

A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously... more A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously reported to show varying degrees of noncompetitive inhibitory activities toward Dengue virus type 2 (Den2) protease. Results obtained from automated docking studies are in agreement with experimental data in which the ligands were shown to bind to sites other than the active site of the protease. The calculated K(i) values are very small, indicating that the ligands bind quite well to the allosteric binding site. Greater inhibition by pinostrobin, compared to the other compounds, can be explained by H-bonding interaction with the backbone carbonyl of Lys74, which is bonded to Asp75 (one of the catalytic triad residues). In addition, structure-activity relationship analysis yields structural information that may be useful for designing more effective therapeutic drugs against dengue virus infections.

Research paper thumbnail of Fractal-like triplet-triplet annihilation kinetics in naphthalene-doped poly(methylmethacrylate)

Chemical Physics Letters, 1988

ABSTRACT

Research paper thumbnail of An AM1 SCF MO study of the reaction of formaldehyde with atomic oxygen

Chemical Physics Letters, 1989

ABSTRACT The decomposition process for formaldehyde in the presence of atomic oxygen has been inv... more ABSTRACT The decomposition process for formaldehyde in the presence of atomic oxygen has been investigated using AM1 semiempirical SCF MO calculations. It is found that for both singlet and triplet energy surfaces the most facile predicted decomposition pathway involves insertion of atomic oxygen to form formic acid followed by a second insertion to produce carbonic acid which then decomposed to CO2 and H2O. Decomposition through a tetrahedral H2CO2 methylenebis(oxy) species, considered by some previous workers, is predicted to be an unfavorable process.

Research paper thumbnail of Mechanism of Glycan Receptor Recognition and Specificity Switch for Avian, Swine and Human Adapted Influenza Virus Hemagglutinins: A Molecular Dynamics Perspective

Biophysical Journal, 2010

Hemagglutinins (HA's) from duck, swine, and human influenza viruses have previously been shown to... more Hemagglutinins (HA's) from duck, swine, and human influenza viruses have previously been shown to prefer avian and human glycan receptor analogues with distinct topological profiles, pentasaccharides LSTa (R-2,3 linkage) and LSTc (R-2,6 linkage), in comparative molecular dynamics studies. On the basis of detailed analyses of the dynamic motions of the receptor binding domains (RBDs) and interaction energy profiles with individual glycan residues, we have identified ∼30 residue positions in the RBD that present distinct profiles with the receptor analogues. Glycan binding constrained the conformational space sampling by the HA. Electrostatic steering appeared to play a key role in glycan binding specificity. The complex dynamic behaviors of the major SSE and trimeric interfaces with or without bound glycans suggested that networks of interactions might account for species specificity in these low affinity and high avidity (multivalent) interactions between different HA and glycans. Contact frequency, energetic decomposition, and H-bond analyses revealed species-specific differences in HA-glycan interaction profiles, not readily discernible from crystal structures alone. Interaction energy profiles indicated that mutation events at the set of residues such as 145, 156, 158, and 222 would favor human or avian receptor analogues, often through interactions with distal asialo-residues. These results correlate well with existing experimental evidence, and suggest new opportunities for simulation-based vaccine and drug development.

Research paper thumbnail of Docking of Noncompetitive Inhibitors into Dengue Virus Type 2 Protease: Understanding the Interactions with Allosteric Binding Sites

Journal of Chemical Information and Modeling, 2008

A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously... more A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously reported to show varying degrees of noncompetitive inhibitory activities toward Dengue virus type 2 (Den2) protease. Results obtained from automated docking studies are in agreement with experimental data in which the ligands were shown to bind to sites other than the active site of the protease. The calculated K(i) values are very small, indicating that the ligands bind quite well to the allosteric binding site. Greater inhibition by pinostrobin, compared to the other compounds, can be explained by H-bonding interaction with the backbone carbonyl of Lys74, which is bonded to Asp75 (one of the catalytic triad residues). In addition, structure-activity relationship analysis yields structural information that may be useful for designing more effective therapeutic drugs against dengue virus infections.