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Sample records for molecular modeling investigations

  1. Binding properties of palmatine to DNA: spectroscopic and molecular modeling investigations.

    PubMed

    Mi, Ran; Tu, Bao; Bai, Xiao-Ting; Chen, Jun; Ouyang, Yu; Hu, Yan-Jun

    2015-12-01

    Palmatine, an isoquinoline alkaloid, is an important medicinal herbal extract with diverse pharmacological and biological properties. In this work, spectroscopic and molecular modeling approaches were employed to reveal the interaction between palmatine and DNA isolated from herring sperm. The absorption spectra and iodide quenching results indicated that groove binding was the main binding mode of palmatine to DNA. Fluorescence studies indicated that the binding constant (K) of palmatine and DNA was ~ 10(4)L·mol(-1). The associated thermodynamic parameters, ΔG, ΔH, and ΔS, indicated that hydrogen bonds and van der Waals forces played major roles in the interaction. The effects of chemical denaturant, thermal denaturation and pH on the interaction were investigated and provided further support for the groove binding mode. In addition to experimental approaches, molecular modeling was conducted to verify binding pattern of palmatine-DNA.

  2. Molecular Modeling and Experimental Investigations of Nonlinear Optical Compounds Monosubstituted Derivatives of Dicyanovinylbenzene

    NASA Technical Reports Server (NTRS)

    Timofeeva, Tatiana V.; Nesterov, Vladimir N.; Antipin, Mikhail Yu.; Clark, Ronald D.; Sanghadasa, Mohan; Cardelino, Beatriz H.; Moore, Craig E.; Frazier, Donald O.

    1999-01-01

    A search for potential nonlinear optical compounds was performed using the Cambridge Structure Database and molecular modeling. We investigated a series of monosubstituted derivatives of dicyanovinylbenzene, since the nonlinear optical (NLO) properties of such derivatives (o-methoxy-dicyanovinylbenzene, DIVA) were studied earlier. The molecular geometry of these compounds was investigated with x-ray analysis and discussed along with the results of molecular mechanics and ab initio quantum chemical calculations. The influence of crystal packing on the planarity of the molecules of this series has been revealed. Two new compounds from the series studied, ortho-F and para-Cl-dicyanovinylbenzene, according to powder measurements, were found to be NLO compounds in the crystal state about 10 times more active than urea. The peculiarities of crystal structure formation in the framework of balance between van der Waals and electrostatic interactions have been discussed. The crystal shape of DIVA and two new NLO compounds have been calculated on the basis of the known crystal structure.

  3. Conformation of receptor-associated PGI2: An investigation by molecular modeling

    NASA Astrophysics Data System (ADS)

    Tsai, Ah-lim; Strobel-Jager, Eva; Wu, Kenneth K.

    1991-04-01

    To elucidate the conformation of receptor-associated prostacyclin (PGI2), we first performed structure-activity correlation analysis of over 200 PGI2 analogues and derived from this analysis several crucial features pertaining to structural requirements for PGI2 activity [Ah-lim Tsai and Kenneth K. Wu, Eicosanoids, 2 (1989) 131-143]. These structural features proved to be useful guidelines for selecting `model molecules' for further investigations by molecular mechanics. By properly selecting four analogues with either rigid or uniquely oriented α-side chain structure for geometric fitting, we succeeded in maximally minimizing the degree of freedom of the carboxylate terminus of PGI2. We were able to define the spatial relationship among the four critical functional groups, i.e., C1-COOH, C6a-O, C11-OH and C15-OH. More information is needed, however, to define the geometry of the ω-side chain, particularly for the moiety beyond C15. Nevertheless, results from structure-activity correlation analysis and molecular modeling provide useful information regarding the conformation of receptor-associated PGI2, which assumes an `elongated' conformation instead of the traditional `hairpin' structure.

  4. Investigation and identification of physical mechanism for enhanced thermal conductivity in nanofluids using molecular level modeling

    NASA Astrophysics Data System (ADS)

    Evans, William John

    Over the last decade a significant research effort has been committed to exploring the thermal transport properties of colloidal suspensions of nanosized solid particles (nanofluids). Initial experiments with Cu-water nanofluids measured up to a 40% increase in thermal conductivity for a mere 0.3% volume fraction of ˜10 nanometer (nm) diameter Cu particles. This increase is significantly larger than predicted by effective medium theory (EMT) of a composite material comprised of well dispersed particles. However, other experimental work on various compositions of nanoparticles and fluids has demonstrated thermal conductivity increases more in line with EMT. A number of possible origins for such behavior have been proposed, but a consensus has yet to emerge. More of the literature attempts to find correlations based on EMT that fit the experimental data rather than exploring the underlying mechanism. The likely candidate theories of liquid layering at the particle-fluid interface, Brownian motion induced heat transfer and particle aggregation are thoroughly explored in this thesis. We undertake a systematic investigation of these most likely mechanisms for enhanced thermal conductivity in nanofluids utilizing various analytical modeling techniques including equilibrium and non-equilibrium molecular dynamics (MD). We demonstrate that aggregation of nanoparticles is the most likely mechanism for enhanced thermal conductivity. We also include the effect of Kapitza interfacial resistance and aggregate shape on nanofluid thermal conductivity. Using our aggregate models, we investigate nanofluid viscosity. Nanoparticle clusters are shown to increase the nanofluid viscosity by up to 75% at 5% volume fraction. Overall the nanofluid exhibits shear thinning behavior.

  5. Investigation of the interaction between five alkaloids and human hemoglobin by fluorescence spectroscopy and molecular modeling.

    PubMed

    He, Wu; Dou, Huanjing; Li, Zhigang; Wang, Xiaogai; Wang, Lvjing; Wang, Ruiyong; Chang, Junbiao

    2014-04-05

    This work studied the interaction of human hemoglobin (HHb) with aminophylline, acefylline, caffeine, theophylline and diprophylline systematically by UV-vis absorption spectroscopy and fluorescence spectroscopy in combination with molecular modeling. Five alkaloids caused the fluorescence quenching of HHb by the formation of alkaloids-HHb complex. The binding constants and thermodynamic parameters were obtained. The hydrophobic and electrostatic interactions were the predominant intermolecular forces to stabilize these complexes. Results of thermodynamic analysis and molecular modeling showed that aminophylline was the strongest quencher and diprophylline was the weakest quencher.

  6. Molecular Modeling

    NASA Astrophysics Data System (ADS)

    Holmes, Jon L.

    1999-06-01

    Molecular modeling has trickled down from the realm of pharmaceutical and research laboratories into the realm of undergraduate chemistry instruction. It has opened avenues for the visualization of chemical concepts that previously were difficult or impossible to convey. I am sure that many of you have developed exercises using the various molecular modeling tools. It is the desire of this Journal to become an avenue for you to share these exercises among your colleagues. It is to this end that Ron Starkey has agreed to edit such a column and to publish not only the description of such exercises, but also the software documents they use. The WWW is the obvious medium to distribute this combination and so accepted submissions will appear online as a feature of JCE Internet. Typical molecular modeling exercise: finding conformation energies. Molecular Modeling Exercises and Experiments is the latest feature column of JCE Internet, joining Conceptual Questions and Challenge Problems, Hal's Picks, and Mathcad in the Chemistry Curriculum. JCE Internet continues to seek submissions in these areas of interest and submissions of general interest. If you have developed materials and would like to submit them, please see our Guide to Submissions for more information. The Chemical Education Resource Shelf, Equipment Buyers Guide, and WWW Site Review would also like to hear about chemistry textbooks and software, equipment, and WWW sites, respectively. Please consult JCE Internet Features to learn more about these resources at JCE Online. Email Announcements Would you like to be informed by email when the latest issue of the Journal is available online? when a new JCE Software title is shipping? when a new JCE Internet article has been published or is available for Open Review? when your subscription is about to expire? A new feature of JCE Online makes this possible. Visit our Guestbook to learn how. When

  7. Investigation on the protein-binding properties of icotinib by spectroscopic and molecular modeling method.

    PubMed

    Zhang, Hua-xin; Xiong, Hang-xing; Li, Li-wei

    2016-05-15

    Icotinib is a highly-selective epidermal growth factor receptor tyrosine kinase inhibitor with preclinical and clinical activity in non-small cell lung cancer, which has been developed as a new targeted anti-tumor drug in China. In this work, the interaction of icotinib and human serum albumin (HSA) were studied by three-dimensional fluorescence spectra, ultraviolet spectra, circular dichroism (CD) spectra, molecular probe and molecular modeling methods. The results showed that icotinib binds to Sudlow's site I in subdomain IIA of HSA molecule, resulting in icotinib-HSA complexes formed at ground state. The number of binding sites, equilibrium constants, and thermodynamic parameters of the reaction were calculated at different temperatures. The negative enthalpy change (ΔH(θ)) and entropy change (ΔS(θ)) indicated that the structure of new complexes was stabilized by hydrogen bonds and van der Waals power. The distance between donor and acceptor was calculated according to Förster's non-radiation resonance energy transfer theory. The structural changes of HSA caused by icotinib binding were detected by synchronous spectra and circular dichroism (CD) spectra. Molecular modeling method was employed to unfold full details of the interaction at molecular level, most of which could be supported by experimental results. The study analyzed the probability that serum albumins act as carriers for this new anticarcinogen and provided fundamental information on the process of delivering icotinib to its target tissues, which might be helpful in understanding the mechanism of icotinib in cancer therapy.

  8. Investigation on the protein-binding properties of icotinib by spectroscopic and molecular modeling method

    NASA Astrophysics Data System (ADS)

    Zhang, Hua-xin; Xiong, Hang-xing; Li, Li-wei

    2016-05-01

    Icotinib is a highly-selective epidermal growth factor receptor tyrosine kinase inhibitor with preclinical and clinical activity in non-small cell lung cancer, which has been developed as a new targeted anti-tumor drug in China. In this work, the interaction of icotinib and human serum albumin (HSA) were studied by three-dimensional fluorescence spectra, ultraviolet spectra, circular dichroism (CD) spectra, molecular probe and molecular modeling methods. The results showed that icotinib binds to Sudlow's site I in subdomain IIA of HSA molecule, resulting in icotinib-HSA complexes formed at ground state. The number of binding sites, equilibrium constants, and thermodynamic parameters of the reaction were calculated at different temperatures. The negative enthalpy change (ΔHθ) and entropy change (ΔSθ) indicated that the structure of new complexes was stabilized by hydrogen bonds and van der Waals power. The distance between donor and acceptor was calculated according to Förster's non-radiation resonance energy transfer theory. The structural changes of HSA caused by icotinib binding were detected by synchronous spectra and circular dichroism (CD) spectra. Molecular modeling method was employed to unfold full details of the interaction at molecular level, most of which could be supported by experimental results. The study analyzed the probability that serum albumins act as carriers for this new anticarcinogen and provided fundamental information on the process of delivering icotinib to its target tissues, which might be helpful in understanding the mechanism of icotinib in cancer therapy.

  9. Continuous distribution model for the investigation of complex molecular architectures near interfaces with scattering techniques

    NASA Astrophysics Data System (ADS)

    Shekhar, Prabhanshu; Nanda, Hirsh; Lösche, Mathias; Heinrich, Frank

    2011-11-01

    Biological membranes are composed of a thermally disordered lipid matrix and therefore require non-crystallographic scattering approaches for structural characterization with x-rays or neutrons. Here we develop a continuous distribution (CD) model to refine neutron or x-ray reflectivity data from complex architectures of organic molecules. The new model is a flexible implementation of the composition-space refinement of interfacial structures to constrain the resulting scattering length density profiles. We show this model increases the precision with which molecular components may be localized within a sample, with a minimal use of free model parameters. We validate the new model by parameterizing all-atom molecular dynamics (MD) simulations of bilayers and by evaluating the neutron reflectivity of a phospholipid bilayer physisorbed to a solid support. The determination of the structural arrangement of a sparsely-tethered bilayer lipid membrane (stBLM) comprised of a multi-component phospholipid bilayer anchored to a gold substrate by a thiolated oligo(ethylene oxide) linker is also demonstrated. From the model we extract the bilayer composition and density of tether points, information which was previously inaccessible for stBLM systems. The new modeling strategy has been implemented into the ga_refl reflectivity data evaluation suite, available through the National Institute of Standards and Technology (NIST) Center for Neutron Research (NCNR).

  10. Selective inhibition of human acetylcholinesterase by xanthine derivatives: in vitro inhibition and molecular modeling investigations.

    PubMed

    Mohamed, Tarek; Osman, Wesseem; Tin, Gary; Rao, Praveen P N

    2013-08-01

    The commonly used beverage and psychostimulant caffeine is known to inhibit human acetylcholinesterase enzyme. This pharmacological activity of caffeine is partly responsible for its cognition enhancing properties. However, the exact mechanisms of its binding to human cholinesterases (acetyl and butyrylcholinesterase; hAChE and hBuChE) are not well known. In this study, we investigated the cholinesterase inhibition by the xanthine derivatives caffeine, pentoxifylline, and propentofylline. Among them, propentofylline was the most potent AChE inhibitor (hAChE IC₅₀=6.40 μM). The hAChE inhibitory potency was of the order: caffeine (hAChE IC₅₀=7.25 μM)50 μM) relative to the reference agent donepezil (hBuChE IC₅₀=13.60 μM). Molecular modeling investigations indicate that caffeine binds primarily in the catalytic site (Ser203, Glu334 and His447) region of hAChE whereas pentoxifylline and propentofylline are able to bind to both the catalytic site and peripheral anionic site due to their increased bulk/size, thereby exhibiting superior AChE inhibition relative to caffeine. In contrast, their lack of hBuChE inhibition is due to a larger binding site and lack of key aromatic amino acids. In summary, our study has important implications in the development of novel caffeine derivatives as selective AChE inhibitors with potential application as cognitive enhancers and to treat various forms of dementia.

  11. Investigations of bisacodyl with modified β-cyclodextrins: Characterization, molecular modeling, and effect of PEG.

    PubMed

    Li, Shanshan; Wang, Lili; Jiang, Jian; Tang, Peixiao; Wang, Qing; Wu, Di; Li, Hui

    2015-12-10

    Bisacodyl inclusion into hydroxypropyl-β-cyclodextrin and 2,6-di-O-methyl-β-cyclodextrin cavities was experimentally and theoretically investigated, and the effect of PEG 4000 on these inclusions was studied. Isothermal calorimetry titration curves indicated that the binary inclusion processes are enthalpy- and entropy-driven. The solid-state complexes were fully characterized by FT-IR, XRPD, DSC and SEM analyses. FT-IR, (1)H NMR, and ROESY studies provided the most favorable encapsulation modes of binary complexes, and results were further confirmed by molecular docking and molecular dynamics studies. The presence of PEG 4000 slightly enhanced encapsulation efficiency, solubility and dissolution rates of the binary complexes. In vivo studies showed that complexes with CDs markedly accelerated gastrointestinal transit time compared with pure bisacodyl, whereas addition of PEG 4000 showed no further significant improvement of the bioavailability.

  12. Adsorption mechanisms of microcystin variant conformations at water-mineral interfaces: A molecular modeling investigation.

    PubMed

    Pochodylo, Amy L; Aoki, Thalia G; Aristilde, Ludmilla

    2016-10-15

    Microcystins (MCs) are potent toxins released during cyanobacterial blooms. Clay minerals are implicated in trapping MCs within soil particles in surface waters and sediments. In the absence of molecular characterization, the relevance of previously proposed adsorption mechanisms is lacking. Towards obtaining this characterization, we conducted Monte Carlo simulations combined with molecular dynamics relaxation of two MC variants, MC-leucine-arginine (MC-LR) and MC-leucine-alanine (MC-LA), adsorbed on hydrated montmorillonite with different electrolytes. The resulting adsorbate structures revealed how MC conformations and aqueous conditions dictate binding interactions at the mineral surface. Electrostatic coupling between the arginine residue and a carboxylate in MC-LR excluded the participation of arginine in mediating adsorption on montmorillonite in a NaCl solution. However, in a CaCl2 solution, the complexation of Ca by two carboxylate moieties in MC-LR changed the MC conformation, which allowed arginine to mediate electrostatic interaction with the mineral. By contrast, due to the lack of arginine in MC-LA, complexation of Ca by only one carboxylate in MC-LA was required to favor Ca-bridging interaction with the mineral. Multiple water-bridged H-bonding interactions were also important in anchoring MCs at the mineral surface. Our modeling results offer molecular insights into the structural and chemical factors that can control the fate of MCs at water-mineral interfaces.

  13. Molecular Modeling of Myrosinase from Brassica oleracea: A Structural Investigation of Sinigrin Interaction

    PubMed Central

    Natarajan, Sathishkumar; Thamilarasan, Senthil Kumar; Park, Jong-In; Chung, Mi-Young; Nou, Ill-Sup

    2015-01-01

    Myrosinase, which is present in cruciferous plant species, plays an important role in the hydrolysis of glycosides such as glucosinolates and is involved in plant defense. Brassicaceae myrosinases are diverse although they share common ancestry, and structural knowledge about myrosinases from cabbage (Brassica oleracea) was needed. To address this, we constructed a three-dimensional model structure of myrosinase based on Sinapis alba structures using Iterative Threading ASSEmbly Refinement server (I-TASSER) webserver, and refined model coordinates were evaluated with ProQ and Verify3D. The resulting model was predicted with β/α fold, ten conserved N-glycosylation sites, and three disulfide bridges. In addition, this model shared features with the known Sinapis alba myrosinase structure. To obtain a better understanding of myrosinase–sinigrin interaction, the refined model was docked using Autodock Vina with crucial key amino acids. The key nucleophile residues GLN207 and GLU427 were found to interact with sinigrin to form a hydrogen bond. Further, 20-ns molecular dynamics simulation was performed to examine myrosinase–sinigrin complex stability, revealing that residue GLU207 maintained its hydrogen bond stability throughout the entire simulation and structural orientation was similar to that of the docked state. This conceptual model should be useful for understanding the structural features of myrosinase and their binding orientation with sinigrin. PMID:26703735

  14. Investigation, expression, and molecular modeling of ORF2, a metagenomic lipolytic enzyme.

    PubMed

    Garcia, Rosmeriana Afnis Marioto; Pereira, Mariana Rangel; Maester, Thaís Carvalho; de Macedo Lemos, Eliana Gertrudes

    2015-04-01

    One clone exhibiting lipolytic activity was selected among 30 positives from a metagenomic library of a microbe consortium specialized in petroleum hydrocarbon degradation. From this clone, a sublibrary was constructed and a metagenome contig was assembled and analyzed using the ORF Finder; thus, it was possible to identify a potential ORF that encodes a lipolytic enzyme, denoted ORF2. This ORF is composed of 1035-bp 345 amino acids and displayed 98 % identity with an alpha/beta hydrolase from Pseudomonas nitroreducens (accession number WP024765380.1). When analyzed against a metagenome database, ORF2 also showed 76 % of sequence identity with a hypothetical protein from a marine metagenome (accession number ECT55726.1). The ProtParam analyses indicated that the recombinant protein ORF2 has a molecular mass approximately 39 kDa, as expected from its amino acid sequence, and based on phylogenetic analysis and molecular modeling, it was possible to suggest that ORF2 is a new member from family V. This enzyme exhibits the catalytic triad and conserved motifs typical from this family, wherein the serine residue is located in the central position of the conserved motif GASMGG. The orf2 gene was cloned in the expression vector pET28a, and the recombinant protein was superexpressed in Escherichia coli BL21(DE3) cells. The lipolytic activity of protein bands presented in a SDS-PAGE gel was confirmed by zymogram analyses, indicating ORF2 activity. These discoveries raise the possibility of employing this protein in biotechnological applications, such as bioremediation.

  15. Alphavirus protease inhibitors from natural sources: A homology modeling and molecular docking investigation.

    PubMed

    Byler, Kendall G; Collins, Jasmine T; Ogungbe, Ifedayo Victor; Setzer, William N

    2016-10-01

    Alphaviruses such as Chikungunya virus (CHIKV), O'Nyong-Nyong virus (ONNV), Ross River virus (RRV), Eastern equine encephalitis virus (EEEV), Venezuelan equine encephalitis virus (VEEV), and Western equine encephalitis virus (WEEV), are mosquito-transmitted viruses that can cause fevers, rash, and rheumatic diseases (CHIKV, ONNV, RRV) or potentially fatal encephalitis (EEEV, VEEV, WEEV) in humans. These diseases are considered neglected tropical diseases for which there are no current antiviral therapies or vaccines available. The alphavirus non-structural protein 2 (nsP2) contains a papain-like protease, which is considered to be a promising target for antiviral drug discovery. In this work, molecular docking analyses have been carried out on a library of 2174 plant-derived natural products (290 alkaloids, 664 terpenoids, 1060 polyphenolics, and 160 miscellaneous phytochemicals) with the nsP2 proteases of CHIKV, ONNV, RRV, EEEV, VEEV, WEEV, as well as Aura virus (AURV), Barmah Forest Virus (BFV), Semliki Forest virus (SFV), and Sindbis virus (SINV) in order to identity structural scaffolds for inhibitor design or discovery. Of the 2174 phytochemicals examined, a total of 127 showed promising docking affinities and poses to one or more of the nsP2 proteases, and this knowledge can be used to guide experimental investigation of potential inhibitors.

  16. Investigation the interaction of Daphnin with human serum albumin using optical spectroscopy and molecular modeling methods

    NASA Astrophysics Data System (ADS)

    Zhu, Jinhua; Wu, Liye; Zhang, Qingyou; Chen, Xingguo; Liu, Xiuhua

    2012-09-01

    The interaction between Daphnin with human serum albumin has been studied for the first time by spectroscopic methods including fluorescence quenching technology, circular dichroism (CD) spectroscopy and Fourier transform infrared (FT-IR) spectroscopy under simulative physiological conditions. The results of fluorescence titration revealed that Daphnin can quench the intrinsic fluorescence of HSA by static quenching and there is a single class of binding site on HSA. In addition, the studies of CD spectroscopy and FT-IR spectroscopy showed that the protein secondary structure changed with increases of α-helices at the drug to protein molar ratio of 2. Furthermore, the thermodynamic functions ΔH0 and ΔS0 for the reaction were calculated to be 11.626 kJ mol-1 and 118.843 J mol-1 K-1 according to Van't Hoff equation. The thermodynamic parameters (ΔH0 and ΔS0) and the molecular modeling study indicated that hydrophobic force played an important role to stabilize the Daphnin-HSA complex, and Daphnin could bind within the subdomain IIA of the HSA.

  17. Nantenine as an acetylcholinesterase inhibitor: SAR, enzyme kinetics and molecular modeling investigations

    PubMed Central

    Pecic, Stevan; McAnuff, Marie A.; Harding, Wayne W.

    2015-01-01

    Nantenine, as well as a number of flexible analogs, were evaluated for acetylcholinesterase (AChE) inhibitory activity in microplate spectrophotometric assays based on Ellman’s method. It was found that the rigid aporphine core of nantenine is an important structural requirement for its anticholinesterase activity. Nantenine showed mixed inhibition kinetics in enzyme assays. Molecular docking experiments suggest that nantenine binds preferentially to the catalytic site of AChE but is also capable of interacting with the peripheral anionic site (PAS) of the enzyme, thus accounting for its mixed inhibition profile. The aporphine core of nantenine may thus be a useful template for the design of novel PAS or dual-site AChE inhibitors. Inhibiting the PAS is desirable for prevention of aggregation of the amyloid peptide Aβ, a major causative factor in the progression of Alzheimer’s disease (AD). PMID:20583856

  18. Investigation of interaction of antibacterial drug sulfamethoxazole with human serum albumin by molecular modeling and multi-spectroscopic method.

    PubMed

    Wang, Qin; Zhang, Sheng-Rui; Ji, Xiaohui

    2014-04-24

    Interaction of sulfamethoxazole (SMX) with human serum albumin (HSA) was investigated by molecular modeling and multi-spectroscopic methods under physiological conditions. The interaction mechanism was firstly predicted through molecular modeling that confirmed the interaction between SMX and HSA. The binding parameters and the thermodynamic parameters at different temperatures for the reaction had been calculated according to the Stern-Volmer, Hill, Scatchard and the Van't Hoff equations, respectively. One independent class of binding site existed during the interaction between HSA and SMX. The binding constants decreased with the increasing temperatures, which meant that the quenching mechanism was a static quenching. The thermodynamic parameters of the reaction, namely standard enthalpy ΔH(0) and entropy ΔS(0), had been calculated to be -16.40 kJ mol(-1) and 32.33 J mol(-1) K(-1), respectively, which suggested that the binding process was exothermic, enthalpy driven and spontaneous. SMX bound to HSA was mainly based on electrostatic interaction, but hydrophobic interactions and hydrogen bonds could not be excluded from the binding. The conformational changes of HSA in the presence of SMX were confirmed by the three-dimensional fluorescence spectroscopy, UV-vis absorption spectroscopy and circular dichroism (CD) spectroscopy. CD data suggested that the protein conformation was altered with the reduction of α-helices from 55.37% to 41.97% at molar ratio of SMX/HSA of 4:1.

  19. Investigation of the interaction between quercetin and human serum albumin by multiple spectra, electrochemical impedance spectra and molecular modeling.

    PubMed

    Dai, Jie; Zou, Ting; Wang, Li; Zhang, Yezhong; Liu, Yi

    2014-12-01

    Quercetin (Qu), a flavonoid compound, exists widely in the human diet and exhibits a variety of pharmacological activities. This work is aimed at studying the effect of Qu on the bioactive protein, human serum albumin (HSA) under simulated biophysical conditions. Multiple spectroscopic methods (including fluorescence and circular dichroism), electrochemical impedance spectra (EIS) and molecular modeling were employed to investigate the interaction between Qu and HSA. The fluorescence quenching and EIS experimental results showed that the fluorescence quenching of HSA was caused by formation of a Qu-HSA complex in the ground state, which belonged to the static quenching mechanism. Based on the calculated thermodynamic parameters, it concluded that the interaction was a spontaneous process and hydrogen bonds combined with van der Waal's forces played a major role in stabilizing the Qu-HSA complex. Molecular modeling results demonstrated that several amino acids participated in the binding process and the formed Qu-HSA complex was stabilized by H-bonding network at site I in sub-domain IIA, which was further confirmed by the site marker competitive experiments. The evidence from circular dichroism (CD) indicated that the secondary structure and microenvironment of HSA were changed. Alterations in the conformation of HSA were observed with a reduction in the amount of α helix from 59.9% (free HSA) to 56% (Qu-HSA complex), indicating a slight unfolding of the protein polypeptides.

  20. Investigation of the behavior of HSA upon binding to amlodipine and propranolol: Spectroscopic and molecular modeling approaches

    NASA Astrophysics Data System (ADS)

    Housaindokht, Mohammad Reza; Rouhbakhsh Zaeri, Zeinab; Bahrololoom, Mahmood; Chamani, Jamshid; Bozorgmehr, Mohammad Reza

    2012-01-01

    The interaction between human serum albumin (HSA) and two drugs - amlodipine and propranolol - was investigated using fluorescence, UV absorption and circular dichroism (CD) spectroscopy. In addition, the binding site was established by applying molecular modeling technique. Fluorescence data suggest that amlodipine will quench the intrinsic fluorescence of HSA; whereas propranolol enhances the fluorescence of HSA. The binding constants for the interaction of amlodipine and propranolol with HSA were found to be 3.63 × 10 5 M -1 and 2.29 × 10 4 M -1, respectively. The percentage of secondary structure feature of each one of the HSA-bound drugs, i.e. the α-helix content, was estimated empirically by circular dichroism. The results indicated that amlodipine causes an increase, and that propranolol leads to a decrease in α-helix content of HSA. The spectroscopic analysis indicates that the binding mechanisms of the two drugs are different from each other. The data obtained by the molecular modeling study indicated that these drugs bind, with different affinity, to different sites located in subdomain IIA and IIIA.

  1. Investigation of Cellular and Molecular Responses to Pulsed Focused Ultrasound in a Mouse Model

    PubMed Central

    Burks, Scott R.; Ziadloo, Ali; Hancock, Hilary A.; Chaudhry, Aneeka; Dean, Dana D.; Lewis, Bobbi K.; Frenkel, Victor; Frank, Joseph A.

    2011-01-01

    Continuous focused ultrasound (cFUS) has been widely used for thermal ablation of tissues, relying on continuous exposures to generate temperatures necessary to induce coagulative necrosis. Pulsed FUS (pFUS) employs non-continuous exposures that lower the rate of energy deposition and allow cooling to occur between pulses, thereby minimizing thermal effects and emphasizing effects created by non-thermal mechanisms of FUS (i.e., acoustic radiation forces and acoustic cavitation). pFUS has shown promise for a variety of applications including drug and nanoparticle delivery; however, little is understood about the effects these exposures have on tissue, especially with regard to cellular pro-homing factors (growth factors, cytokines, and cell adhesion molecules). We examined changes in murine hamstring muscle following pFUS or cFUS and demonstrate that pFUS, unlike cFUS, has little effect on the histological integrity of muscle and does not induce cell death. Infiltration of macrophages was observed 3 and 8 days following pFUS or cFUS exposures. pFUS increased expression of several cytokines (e.g., IL-1α, IL-1β, TNFα, INFγ, MIP-1α, MCP-1, and GMCSF) creating a local cytokine gradient on days 0 and 1 post-pFUS that returns to baseline levels by day 3 post-pFUS. pFUS exposures induced upregulation of other signaling molecules (e.g., VEGF, FGF, PlGF, HGF, and SDF-1α) and cell adhesion molecules (e.g., ICAM-1 and VCAM-1) on muscle vasculature. The observed molecular changes in muscle following pFUS may be utilized to target cellular therapies by increasing homing to areas of pathology. PMID:21931834

  2. Pairing preferences of the model mono-valence mono-atomic ions investigated by molecular simulation

    SciTech Connect

    Zhang, Qiang; Zhang, Ruiting; Zhao, Ying; Li, HuanHuan; Zhuang, Wei E-mail: gaoyq@pku.edu.cn; Gao, Yi Qin E-mail: gaoyq@pku.edu.cn

    2014-05-14

    We carried out a series of potential of mean force calculations to study the pairing preferences of a series of model mono-atomic 1:1 ions with evenly varied sizes. The probabilities of forming the contact ion pair (CIP) and the single water separate ion pair (SIP) were presented in the two-dimensional plots with respect to the ion sizes. The pairing preferences reflected in these plots largely agree with the empirical rule of matching ion sizes in the small and big size regions. In the region that the ion sizes are close to the size of the water molecule; however, a significant deviation from this conventional rule is observed. Our further analysis indicated that this deviation originates from the competition between CIP and the water bridging SIP state. The competition is mainly an enthalpy modulated phenomenon in which the existing of the water bridging plays a significant role.

  3. Pairing preferences of the model mono-valence mono-atomic ions investigated by molecular simulation.

    PubMed

    Zhang, Qiang; Zhang, Ruiting; Zhao, Ying; Li, HuanHuan; Gao, Yi Qin; Zhuang, Wei

    2014-05-14

    We carried out a series of potential of mean force calculations to study the pairing preferences of a series of model mono-atomic 1:1 ions with evenly varied sizes. The probabilities of forming the contact ion pair (CIP) and the single water separate ion pair (SIP) were presented in the two-dimensional plots with respect to the ion sizes. The pairing preferences reflected in these plots largely agree with the empirical rule of matching ion sizes in the small and big size regions. In the region that the ion sizes are close to the size of the water molecule; however, a significant deviation from this conventional rule is observed. Our further analysis indicated that this deviation originates from the competition between CIP and the water bridging SIP state. The competition is mainly an enthalpy modulated phenomenon in which the existing of the water bridging plays a significant role.

  4. Multi-spectroscopic and molecular modelling approach to investigate the interaction of riboflavin with human serum albumin.

    PubMed

    Alam, Md Maroof; Abul Qais, Faizan; Ahmad, Iqbal; Alam, Parvez; Hasan Khan, Rizwan; Naseem, Imrana

    2017-03-09

    Riboflavin (RF) plays an important role in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Human serum albumin (HSA) is an important protein involved in the transportation of drugs, hormones, fatty acid and other molecules which determine the biodistribution and physiological fate of these molecules. In this study, we have investigated the interaction of riboflavin RF with HSA under simulative physiological conditions using various biophysical, calorimetric and molecular docking techniques. Results demonstrate the formation of riboflavin-HSA complex with binding constant in the order of 10(4) M(-1). Fluorescence spectroscopy confirms intermediate strength having a static mode of quenching with stoichiometry of 1:1. Experimental results suggest that the binding site of riboflavin mainly resides in sub-domain IIA of HSA and that ligand interaction increases the α-helical content of HSA. These parameters were further verified by isothermal titration calorimetry ITC which confirms the thermodynamic parameters obtained by fluorescence spectroscopy. Molecular docking was employed to suggest a binding model. Based on thermodynamic, spectroscopic and computational observations it can be concluded that HSA-riboflavin complex is mainly stabilized by various non-covalent forces with binding energy of -7.2 kcal mol(-1).

  5. Open Source Molecular Modeling

    PubMed Central

    Pirhadi, Somayeh; Sunseri, Jocelyn; Koes, David Ryan

    2016-01-01

    The success of molecular modeling and computational chemistry efforts are, by definition, dependent on quality software applications. Open source software development provides many advantages to users of modeling applications, not the least of which is that the software is free and completely extendable. In this review we categorize, enumerate, and describe available open source software packages for molecular modeling and computational chemistry. PMID:27631126

  6. Flurbiprofen–antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling

    PubMed Central

    Ashraf, Zaman; Alamgeer; Kanwal, Munazza; Hassan, Mubashir; Abdullah, Sahar; Waheed, Mamuna; Ahsan, Haseeb; Kim, Song Ja

    2016-01-01

    Flurbiprofen–antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (–COOH) was temporarily masked by esterification with phenolic –OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P<0.001) reduced the inflammation against carrageenan and egg albumin-induced paw edema at 4 hours of study. The reduction in the size of the inflamed paw showed that most of the compounds inhibited the later phase of inflammation. The prodrug 2-oxo-2H-chromen-7-yl-2-(2-fluorobiphenyl-4-yl)propanoate (4b) showed significant reduction in paw licking with percentage inhibition of 58%. It also exhibited higher analgesic activity, reducing the number of writhes with a percentage of 75%, whereas flurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer’s yeast-induced pyrexia model, and significant (P<0.001) reduction in rectal temperature was shown by all prodrugs at all times of assessment. The results of ulcerogenic activity showed that all prodrugs produced less GI irritation than flurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2) proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities

  7. Investigations on the interactions of diclofenac sodium with HSA and ctDNA using molecular modeling and multispectroscopic methods

    NASA Astrophysics Data System (ADS)

    Cui, Yanrui; Hao, Erjun; Hui, Guangquan; Guo, Wei; Cui, Fengling

    2013-06-01

    A tentative study on interaction of diclofenac sodium (DF-Na) with human serum albumin (HSA) and calf thymus DNA (ctDNA) was conducted by using multi-spectroscopic and molecular modeling techniques under simulative physiological conditions. The results of spectroscopic measurements suggested that the quenching mechanisms were static quenching. Three-dimensional fluorescence spectroscopy clearly demonstrated the occurrence of conformational changes of HSA with addition of DF-Na. In addition, competitive studies with ethidium bromide (EB) have shown that DF-Na can bind to ctDNA relatively strong via groove binding. Based on the values of thermodynamic parameters and the results of molecular modeling, it was confirmed that hydrophobic forces and hydrogen bond were the mainly binding forces in DF-Na-HSA and DF-Na-DNA systems. The binding distance between DF-Na and HSA was also determined using the theory of the Förster energy transference.

  8. Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic nephropathy animals: investigating mechanism of interaction by molecular modeling studies.

    PubMed

    Tripathi, Alok Shiomurti; Timiri, Ajay Kumar; Mazumder, Papiya Mitra; Chandewar, Anil

    2015-10-01

    The present study evaluates possible drug interactions between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ)-induced diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction based on molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg kg(-1), i.p.) and was confirmed by assessing blood and urine biochemical parameters 28 days after induction. Selected DN animals were used to explore the drug interaction between GLIM (0.5 mg kg(-1), p.o.) and SIL (2.5 mg kg(-1), p.o.) on the 29th and 70th day of the protocol. Possible drug interaction was assessed by evaluating the plasma drug concentration using HPLC-UV and changes in biochemical parameters in blood and urine were also determined. The mechanism of the interaction was postulated from the results of a molecular modeling study using the Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in blood and urine biochemical parameters in STZ-treated groups. The concentration of SIL increased significantly (P < 0.001) in rat plasma when co-administered with GLIM on the 70th day of the protocol. Molecular modeling revealed important interactions with rat serum albumin and CYP2C9. GLIM has a strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL, whereas for CYP2C9, GLIM forms a stronger hydrogen bond than SIL with polar contacts and hydrophobic interactions. The present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals, and the mechanism is supported by molecular modeling studies.

  9. Open source molecular modeling.

    PubMed

    Pirhadi, Somayeh; Sunseri, Jocelyn; Koes, David Ryan

    2016-09-01

    The success of molecular modeling and computational chemistry efforts are, by definition, dependent on quality software applications. Open source software development provides many advantages to users of modeling applications, not the least of which is that the software is free and completely extendable. In this review we categorize, enumerate, and describe available open source software packages for molecular modeling and computational chemistry. An updated online version of this catalog can be found at https://opensourcemolecularmodeling.github.io.

  10. Basic amphipathic model peptides: Structural investigations in solution, studied by circular dichroism, fluorescence, analytical ultracentrifugation and molecular modelling

    NASA Astrophysics Data System (ADS)

    Mangavel, C.; Sy, D.; Reynaud, J. A.

    1999-05-01

    A twenty amino acid residue long amphipathic peptide made of ten leucine and ten lysine residues and four derivatives, in which a tryptophan, as a fluorescent probe, is substituted for a leucine, are studied. The peptides in water are mainly in an unordered conformation (~90%), and undergo a two state reversible transition upon heating, leading to a partially helical conformation (cold denaturation). Time resolved fluorescence results show that fluorescence decay for the four Trp containing peptides is best described by triple fluorescence decay kinetics. In TFE/water mixture, peptides adopt a single α-helix conformation but the Leu-Trp9 substitution leads to an effective helix destabilizing effect. In salted media, the peptides are fully helical and present a great tendency to self associate by bringing the hydrophobic faces of helices into close contact. This proceeds in non-cooperative multisteps leading to the formation of α helix aggregates with various degrees of complexation. Using modelling, the relative hydrophobic surface areas accessible to water molecules in n-mer structures are calculated and discussed. Nous avons étudié un peptide amphipathique composé de dix lysine et dix leucine, ainsi que quatre dérivés comportant un résidu tryptophane pour les études par fluorescence. Dans l'eau, les peptides ne sont pas structurés (~90%), et se structurent partiellement en hélice α par chauffage (dénaturation froide). Les mesures de déclin de fluorescence font apparaître une cinétique à trois temps de vie. Dans un mélange eau/TFE, les peptides adoptent une conformation en hélice α, mais la substitution Leu-Trp9 possède un effet déstabilisant. En mileu salin, les peptides sont totalement hélicoïdaux et ont tendance à s'agréger de façon à regrouper leur face hydrophobe. Ce processus se fait en plusieurs étapes avec des agrégats de taille variable. L'existence de tels agrégats est discutée sur la base de la modélisation mol

  11. Molecular Models in Biology

    ERIC Educational Resources Information Center

    Goodman, Richard E.

    1970-01-01

    Describes types of molecular models (ball-and-stick, framework, and space-filling) and evaluates commercially available kits. Gives instructions for constructive models from polystyrene balls and pipe-cleaners. Models are useful for class demonstrations although not sufficiently accurate for research use. Illustrations show biologically important…

  12. Generation of a 3D model for human GABA transporter hGAT-1 using molecular modeling and investigation of the binding of GABA.

    PubMed

    Wein, Thomas; Wanner, Klaus T

    2010-01-01

    A three-dimensional model of the human Na(+)/Cl(-)-dependent gamma-aminobutyric acid (GABA) transporter hGAT-1 was developed by homology modeling and refined by subsequent molecular modeling using the crystal structure of a bacterial homologue leucine transporter from Aquifex aeolicus (LeuT(Aa)) as the template. Protein structure quality checks show that the resulting structure is particularly suited for the analysis of the substrate binding pocket and virtual screening experiments. Interactions of GABA and the substrate binding pocket were investigated using docking studies. The difference of 6 out of 13 substrate interacting side chains between hGAT-1 and LeuT(Aa) lead to the different substrate preference which can be explained using our three-dimensional model of hGAT-1. In particular the replacement of serine 256 and isoleucine 359 in LeuT(Aa) with glycine and threonine in hGAT-1 seems to facilitate the selection of GABA as the main substrate by changing the hydrogen bonding pattern in the active site to the amino group of the substrate. For a set of 12 compounds flexible docking experiments were performed using LigandFit in combination with the Jain scoring function. With few exceptions the obtained rank order of potency was in line with experimental data. Thus, the method can be assumed to give at least a rough estimate of the potency of the potential of GABA uptake inhibitors.

  13. Molecular modeling of peptides.

    PubMed

    Kuczera, Krzysztof

    2015-01-01

    This article presents a review of the field of molecular modeling of peptides. The main focus is on atomistic modeling with molecular mechanics potentials. The description of peptide conformations and solvation through potentials is discussed. Several important computer simulation methods are briefly introduced, including molecular dynamics, accelerated sampling approaches such as replica-exchange and metadynamics, free energy simulations and kinetic network models like Milestoning. Examples of recent applications for predictions of structure, kinetics, and interactions of peptides with complex environments are described. The reliability of current simulation methods is analyzed by comparison of computational predictions obtained using different models with each other and with experimental data. A brief discussion of coarse-grained modeling and future directions is also presented.

  14. Investigations on the Interactions of 5-Fluorouracil with Herring Sperm DNA: Steady State/Time Resolved and Molecular Modeling Studies

    NASA Astrophysics Data System (ADS)

    Chinnathambi, Shanmugavel; Karthikeyan, Subramani; Velmurugan, Devadasan; Hanagata, Nobutaka; Aruna, Prakasarao; Ganesan, Singaravelu

    2015-04-01

    In the present study, the interaction of 5-Fluorouracil with herring sperm DNA is reported using spectroscopic and molecular modeling techniques. This binding study of 5-FU with hs-DNA is of paramount importance in understanding chemico-biological interactions for drug design, pharmacy and biochemistry without altering the original structure. The challenge of the study was to find the exact binding mode of the drug 5-Fluorouracil with hs-DNA. From the absorption studies, a hyperchromic effect was observed for the herring sperm DNA in the presence of 5-Fluorouracil and a binding constant of 6.153 × 103 M-1 for 5-Fluorouracil reveals the existence of weak interaction between the 5-Fluorouracil and herring sperm DNA. Ethidium bromide loaded herring sperm DNA showed a quenching in the fluorescence intensity after the addition of 5-Fluorouracil. The binding constants for 5-Fluorouracil stranded DNA and competitive bindings of 5-FU interacting with DNA-EB systems were examined by fluorescence spectra. The Stern-Volmer plots and fluorescence lifetime results confirm the static quenching nature of the drug-DNA complex. The binding constant Kb was 2.5 × 104 L mol-1 and the number of binding sites are 1.17. The 5-FU on DNA system was calculated using double logarithmic plot. From the Forster nonradiative energy transfer study it has been found that the distance of 5-FU from DNA was 4.24 nm. In addition to the spectroscopic results, the molecular modeling studies also revealed the major groove binding as well as the partial intercalation mode of binding between the 5-Fluorouracil and herring sperm DNA. The binding energy and major groove binding as -6.04 kcal mol-1 and -6.31 kcal mol-1 were calculated from the modeling studies. All the testimonies manifested that binding modes between 5-Fluorouracil and DNA were evidenced to be groove binding and in partial intercalative mode.

  15. A comparison investigation of DNP-binding effects to HSA and HTF by spectroscopic and molecular modeling techniques.

    PubMed

    Zolfagharzadeh, Mahboobeh; Pirouzi, Maliheh; Asoodeh, Ahmad; Saberi, Mohammad Reza; Chamani, Jamshidkhan

    2014-12-01

    This paper describes the interaction between 2,4-dinitrophenol (DNP) with the two drug carrier proteins - human serum albumin (HSA) and human holo transferrin (HTF). Hence, binding characteristics of DNP to HSA and HTF were analyzed by spectroscopic and molecular modeling techniques. Based on results obtained from fluorescence spectroscopy, DNP had a strong ability to quench the intrinsic fluorescence of HSA and HTF through a static quenching procedure. The binding constant and the number of binding sites were calculated as 2.3 × 10(11) M(-1) and .98 for HSA, and 1.7 × 10(11) M(-1) and 1.06 for HTF, respectively. In addition, synchronous fluorescence results showed that the microenvironment of Trp had a slight tendency of increasing its hydrophobicity, whereas the microenvironment of the Tyr residues of HSA did not change and that of HTF showed a significant trend (red shift of about 4 nm) of an increase in polarity. The distance between donor and acceptor was obtained by the Förster energy according to fluorescence resonance energy transfer, and was found to be 3.99 and 3.72 nm for HSA and HTF, respectively. The critical induced aggregation concentration (CCIAC) of the drug on both proteins was determined and confirmed by an inflection point of the zeta potential behavior. Circular dichroism data revealed that the presence of DNP caused a decrease of the α-helical content of HSA and HTF, and induced a remarkable mild denaturation of both proteins. The molecular modeling data confirmed our experimental results. This study is deemed useful for determining drug dosage.

  16. Investigating Molecular Mechanisms of Activation and Mutation of the HER2 Receptor Tyrosine Kinase through Computational Modeling and Simulation.

    PubMed

    Telesco, Shannon E; Shih, Andrew; Liu, Yingting; Radhakrishnan, Ravi

    2011-01-01

    Human epidermal growth factor receptor 2 (HER2)/ErbB2 is a receptor tyrosine kinase belonging to the EGFR/ErbB family and is overexpressed in 20-30% of human breast cancers. Since there is a growing effort to develop pharmacological inhibitors of the HER2 kinase for the treatment of breast cancer, it is clinically valuable to rationalize how specific mutations impact the molecular mechanism of receptor activation. Although several crystal structures of the ErbB kinases have been solved, the precise mechanism of HER2 activation remains unknown, and it has been suggested that HER2 is unique in its requirement for phosphorylation of Y877, a key tyrosine residue located in the activation loop (A-loop). In our studies, discussed here, we have investigated the mechanisms that are important in HER2 kinase domain regulation and compared them with the other ErbB family members, namely EGFR and ErbB4, to determine the molecular basis for HER2's unique mode of activation. We apply computational simulation techniques at the atomic level and at the electronic structure (quantum mechanical) level to elucidate details of the mechanisms governing the kinase domains of these ErbB members. Through analysis of our simulation results, we have discovered potential regulatory mechanisms common to EGFR, HER2, and ErbB4, including a tight coupling between the A-loop and catalytic loop that may contribute to alignment of residues required for catalysis in the active kinase. We further postulate an autoinhibitory mechanism whereby the inactive kinase is stabilized through sequestration of catalytic residues. In HER2, we also predict a role for phosphorylated Y877 in bridging a network of hydrogen bonds that fasten the A-loop in its active conformation, suggesting that HER2 may be unique among the ErbB members in requiring A-loop tyrosine phosphorylation for functionality. In EGFR, HER2, and ErbB4, we discuss the possible effects of activating mutations. Delineation of the activation

  17. Molecular dynamics simulations of model trans-membrane peptides in lipid bilayers: a systematic investigation of hydrophobic mismatch.

    PubMed

    Kandasamy, Senthil K; Larson, Ronald G

    2006-04-01

    Hydrophobic mismatch, which is the difference between the hydrophobic length of trans-membrane segments of a protein and the hydrophobic width of the surrounding lipid bilayer, is known to play a role in membrane protein function. We have performed molecular dynamics simulations of trans-membrane KALP peptides (sequence: GKK(LA)nLKKA) in phospholipid bilayers to investigate hydrophobic mismatch alleviation mechanisms. By varying systematically the length of the peptide (KALP15, KALP19, KALP23, KALP27, and KALP31) and the lipid hydrophobic length (DLPC, DMPC, and DPPC), a wide range of mismatch conditions were studied. Simulations of durations of 50-200 ns show that under positive mismatch, the system alleviates the mismatch predominantly by tilting the peptide and to a smaller extent by increased lipid ordering in the immediate vicinity of the peptide. Under negative mismatch, alleviation takes place by a combination of local bilayer bending and the snorkeling of the lysine residues of the peptide. Simulations performed at a higher peptide/lipid molar ratio (1:25) reveal slower dynamics of both the peptide and lipid relative to those at a lower peptide/lipid ratio (1:128). The lysine residues have favorable interactions with specific oxygen atoms of the phospholipid headgroups, indicating the preferred localization of these residues at the lipid/water interface.

  18. Molecular Dynamics Simulations of Model Trans-Membrane Peptides in Lipid Bilayers: A Systematic Investigation of Hydrophobic Mismatch

    PubMed Central

    Kandasamy, Senthil K.; Larson, Ronald G.

    2006-01-01

    Hydrophobic mismatch, which is the difference between the hydrophobic length of trans-membrane segments of a protein and the hydrophobic width of the surrounding lipid bilayer, is known to play a role in membrane protein function. We have performed molecular dynamics simulations of trans-membrane KALP peptides (sequence: GKK(LA)nLKKA) in phospholipid bilayers to investigate hydrophobic mismatch alleviation mechanisms. By varying systematically the length of the peptide (KALP15, KALP19, KALP23, KALP27, and KALP31) and the lipid hydrophobic length (DLPC, DMPC, and DPPC), a wide range of mismatch conditions were studied. Simulations of durations of 50–200 ns show that under positive mismatch, the system alleviates the mismatch predominantly by tilting the peptide and to a smaller extent by increased lipid ordering in the immediate vicinity of the peptide. Under negative mismatch, alleviation takes place by a combination of local bilayer bending and the snorkeling of the lysine residues of the peptide. Simulations performed at a higher peptide/lipid molar ratio (1:25) reveal slower dynamics of both the peptide and lipid relative to those at a lower peptide/lipid ratio (1:128). The lysine residues have favorable interactions with specific oxygen atoms of the phospholipid headgroups, indicating the preferred localization of these residues at the lipid/water interface. PMID:16428278

  19. Theoretical investigation of two model systems for molecular photoswitch functionality. I. 2-(4-nitropyrimidin-2-yl)ethenol

    NASA Astrophysics Data System (ADS)

    Woywod, Clemens; Csehi, András; Halász, Gábor J.; Ruud, Kenneth; Vibók, Ágnes

    2014-03-01

    The ground and five lowest-lying electronically excited singlet states of 2-(4-nitropyrimidin-2-yl)ethenol (NPE) have been studied theoretically using the complete active space self-consistent-field (CASSCF), Møller-Plesset second-order perturbation theory (MP2) and second-order multi-configurational perturbation theory (CASPT2) methods. The molecule can be regarded as being composed of a frame and a crane component and is characterised by the existence of two planar minima of similar energy on the ground-state potential energy (PE) surface. This work explores the possibility of an excited-state intramolecular hydrogen transfer (ESIHT) process in NPE. A hypothetical reaction coordinate has been constructed for NPE. State-averaged CASSCF and CASPT2 calculations of the six lowest-lying singlet states have been performed for the isomerisation. Adiabatic and simplified quasi-diabatic PE and transition dipole moment functions have been constructed. The computations indicate that there exist substantial barriers for the rotation process on the adiabatic PE surfaces of all the five excited states investigated. The six quasi-diabatic electronic states considered here decompose into two classes based on whether the electronic wave functions depend weakly or strongly on the nuclear displacement, subject to the effect of the torsion on relevant molecular orbitals.

  20. Investigation of the Interaction between 1,3-Diazaheterocyclic Compounds and the Fat Mass and Obesity-Associated Protein by Fluorescence Spectroscopy and Molecular Modeling.

    PubMed

    Zhang, Lijiao; Ren, Ting; Tian, Xianhai; Wang, Zechun; Yu, Wenquan; Wang, Ruiyong; Chang, Junbiao

    2017-01-01

    In this paper, The binding of twelve 1,3-diazaheterocyclic compounds (1a-1 l) to the fat mass and obesity-associated (FTO) protein was investigated by fluorescence, UV-vis absorption spectroscopy and molecular modeling. Results indicated that the intrinsic fluorescence of FTO is quenched by the nine compounds (1a-1i) with a static quenching procedure. No interaction was observed between FTO protein and compounds (1j-1 l). The thermodynamic parameters obtained from the fluorescence data showed that the hydrophobic force played a major role in stabilizing the complex. The results of synchronous and three-dimensional fluorescence spectra showed that the conformation of FTO was changed. In addition, the influence of molecular structure on the quenching effect has been investigated.

  1. Investigations on the interactions between naphthalimide-based anti-tumor drugs and human serum albumin by spectroscopic and molecular modeling methods.

    PubMed

    Cheng, Huiyuan; Zou, Ting; Xu, Yongliang; Wang, Ying; Wu, Aibin; Dai, Jie; Zhang, Yezhong; Liu, Yi

    2016-02-01

    The interactions between the three kinds of naphthalimide-based anti-tumor drugs (NADA, NADB, NADC) and human serum albumin (HSA) under simulated physiological conditions were investigated by fluorescence spectroscopy, circular dichroism spectroscopy and molecular modeling. The results of the fluorescence quenching spectroscopy showed that the quenching mechanisms for different drugs were static and their affinity was in a descending order of NADA > NADB > NADC. The relative thermodynamic parameters indicated that hydrophobic force was the predominant intermolecular force in the binding of NAD to HSA, while van der Waals interactions and hydrogen bonds could not be ignored. The results of site marker competitive experiment confirmed that the binding site of HSA primarily took place in site I. Furthermore, the molecular modeling study was consistent with these results. The study of circular dichroism spectra demonstrated that the presence of NADs decreased the α-helical content of HSA and induced the change of the secondary structure of HSA.

  2. Interaction of O and OH radicals with a simple model system for lipids in the skin barrier: a reactive molecular dynamics investigation for plasma medicine

    NASA Astrophysics Data System (ADS)

    Van der Paal, Jonas; Aernouts, Stefaan; van Duin, Adri C. T.; Neyts, Erik C.; Bogaerts, Annemie

    2013-10-01

    Plasma medicine has been claimed to provide a novel route to heal wounds and regenerate skin, although very little is currently known about the elementary processes taking place. We carried out a series of ReaxFF-based reactive molecular dynamics simulations to investigate the interaction of O and OH radicals with lipids, more specifically with α-linolenic acid as a model for the free fatty acids present in the upper skin layer. Our calculations predict that the O and OH radicals most typically abstract a H atom from the fatty acids, which can lead to the formation of a conjugated double bond, but also to the incorporation of alcohol or aldehyde groups, thereby increasing the hydrophilic character of the fatty acids and changing the general lipid composition of the skin. Within the limitations of the investigated model, no formation of possibly toxic products was observed.

  3. Synthesis of F16 conjugated with 5-fluorouracil and biophysical investigation of its interaction with bovine serum albumin by a spectroscopic and molecular modeling approach.

    PubMed

    Xiang, Chen; Li, Dong-Wei; Qi, Zu-De; Jiang, Feng-Lei; Ge, Yu-Shu; Liu, Yi

    2013-01-01

    5-Fluorouracil (5-FU) has been widely used as a chemotherapy agent in the treatment of many types of solid tumors. Investigation of its antimetabolites led to the development of an entire class of fluorinated pyrimidines. However, the toxicity profile associated with 5-FU is significant and includes diarrhea, mucositis, hand-foot syndrome and myelosuppression. In aiming at reducing of the side effects of 5-FU, we have designed and synthesized delocalized lipophilic cations (DLCs) as a vehicle for the delivery of 5-FU. DLCs accumulate selectively in the mitochondria of cancer cells because of the high mitochondrial transmembrane potential (ΔΨm). Many DLCs exhibited anti-cancer efficacy and were explored as potential anti-cancer drugs based on their selective accumulation in the mitochondria of cancer cells. F16, the DLC we used as a vehicle, is a small molecule that selectively inhibits tumor cell growth and dissipates mitochondrial membrane potential. The binding of the conjugate F16-5-FU to bovine serum albumin (BSA) was investigated using spectroscopic and molecular modeling approaches. Fluorescence quenching constants were determined using the Stern-Volmer equation to provide a measure of the binding affinity between F16-5-FU and BSA. The activation energy of the interaction between F16-5-FU and BSA was calculated and the unusually high value was discussed in terms of the special structural block indicated by the molecular modeling approach. Molecular modeling showed that F16-5-FU binds to human serum albumin in site II, which is consistent with the results of site-competitive replacement experiments. It is suggested that hydrophobic and polar forces played important roles in the binding reaction, in accordance with the results of thermodynamic experiments.

  4. Testing the limits of sensitivity in a solid-state structural investigation by combined X-ray powder diffraction, solid-state NMR, and molecular modelling.

    PubMed

    Filip, Xenia; Borodi, Gheorghe; Filip, Claudiu

    2011-10-28

    A solid state structural investigation of ethoxzolamide is performed on microcrystalline powder by using a multi-technique approach that combines X-ray powder diffraction (XRPD) data analysis based on direct space methods with information from (13)C((15)N) solid-state Nuclear Magnetic Resonance (SS-NMR) and molecular modeling. Quantum chemical computations of the crystal were employed for geometry optimization and chemical shift calculations based on the Gauge Including Projector Augmented-Wave (GIPAW) method, whereas a systematic search in the conformational space was performed on the isolated molecule using a molecular mechanics (MM) approach. The applied methodology proved useful for: (i) removing ambiguities in the XRPD crystal structure determination process and further refining the derived structure solutions, and (ii) getting important insights into the relationship between the complex network of non-covalent interactions and the induced supra-molecular architectures/crystal packing patterns. It was found that ethoxzolamide provides an ideal case study for testing the accuracy with which this methodology allows to distinguish between various structural features emerging from the analysis of the powder diffraction data.

  5. Techniques for Investigating Molecular Toxicology of Nanomaterials.

    PubMed

    Wang, Yanli; Li, Chenchen; Yao, Chenjie; Ding, Lin; Lei, Zhendong; Wu, Minghong

    2016-06-01

    Nanotechnology has been a rapidly developing field in the past few decades, resulting in the more and more exposure of nanomaterials to human. The increased applications of nanomaterials for industrial, commercial and life purposes, such as fillers, catalysts, semiconductors, paints, cosmetic additives and drug carriers, have caused both obvious and potential impacts on human health and environment. Nanotoxicology is used to study the safety of nanomaterials and has grown at the historic moment. Molecular toxicology is a new subdiscipline to study the interactions and impacts of materials at the molecular level. To better understand the relationship between the molecular toxicology and nanomaterials, this review summarizes the typical techniques and methods in molecular toxicology which are applied when investigating the toxicology of nanomaterials and include six categories: namely; genetic mutation detection, gene expression analysis, DNA damage detection, chromosomal aberration analysis, proteomics, and metabolomics. Each category involves several experimental techniques and methods.

  6. Using multi-compartment ensemble modeling as an investigative tool of spatially distributed biophysical balances: application to hippocampal oriens-lacunosum/moleculare (O-LM) cells.

    PubMed

    Sekulić, Vladislav; Lawrence, J Josh; Skinner, Frances K

    2014-01-01

    Multi-compartmental models of neurons provide insight into the complex, integrative properties of dendrites. Because it is not feasible to experimentally determine the exact density and kinetics of each channel type in every neuronal compartment, an essential goal in developing models is to help characterize these properties. To address biological variability inherent in a given neuronal type, there has been a shift away from using hand-tuned models towards using ensembles or populations of models. In collectively capturing a neuron's output, ensemble modeling approaches uncover important conductance balances that control neuronal dynamics. However, conductances are never entirely known for a given neuron class in terms of its types, densities, kinetics and distributions. Thus, any multi-compartment model will always be incomplete. In this work, our main goal is to use ensemble modeling as an investigative tool of a neuron's biophysical balances, where the cycling between experiment and model is a design criterion from the start. We consider oriens-lacunosum/moleculare (O-LM) interneurons, a prominent interneuron subtype that plays an essential gating role of information flow in hippocampus. O-LM cells express the hyperpolarization-activated current (Ih). Although dendritic Ih could have a major influence on the integrative properties of O-LM cells, the compartmental distribution of Ih on O-LM dendrites is not known. Using a high-performance computing cluster, we generated a database of models that included those with or without dendritic Ih. A range of conductance values for nine different conductance types were used, and different morphologies explored. Models were quantified and ranked based on minimal error compared to a dataset of O-LM cell electrophysiological properties. Co-regulatory balances between conductances were revealed, two of which were dependent on the presence of dendritic Ih. These findings inform future experiments that differentiate between

  7. Using Multi-Compartment Ensemble Modeling As an Investigative Tool of Spatially Distributed Biophysical Balances: Application to Hippocampal Oriens-Lacunosum/Moleculare (O-LM) Cells

    PubMed Central

    Sekulić, Vladislav; Lawrence, J. Josh; Skinner, Frances K.

    2014-01-01

    Multi-compartmental models of neurons provide insight into the complex, integrative properties of dendrites. Because it is not feasible to experimentally determine the exact density and kinetics of each channel type in every neuronal compartment, an essential goal in developing models is to help characterize these properties. To address biological variability inherent in a given neuronal type, there has been a shift away from using hand-tuned models towards using ensembles or populations of models. In collectively capturing a neuron's output, ensemble modeling approaches uncover important conductance balances that control neuronal dynamics. However, conductances are never entirely known for a given neuron class in terms of its types, densities, kinetics and distributions. Thus, any multi-compartment model will always be incomplete. In this work, our main goal is to use ensemble modeling as an investigative tool of a neuron's biophysical balances, where the cycling between experiment and model is a design criterion from the start. We consider oriens-lacunosum/moleculare (O-LM) interneurons, a prominent interneuron subtype that plays an essential gating role of information flow in hippocampus. O-LM cells express the hyperpolarization-activated current (Ih). Although dendritic Ih could have a major influence on the integrative properties of O-LM cells, the compartmental distribution of Ih on O-LM dendrites is not known. Using a high-performance computing cluster, we generated a database of models that included those with or without dendritic Ih. A range of conductance values for nine different conductance types were used, and different morphologies explored. Models were quantified and ranked based on minimal error compared to a dataset of O-LM cell electrophysiological properties. Co-regulatory balances between conductances were revealed, two of which were dependent on the presence of dendritic Ih. These findings inform future experiments that differentiate between

  8. Investigation of molecular mechanisms of action of chelating drugs on protein-lipid model membranes by X-ray fluorescence

    SciTech Connect

    Novikova, N. N.; Zheludeva, S. I.; Koval'chuk, M. V.; Stepina, N. D.; Erko, A. I.; Yur'eva, E. A.

    2009-12-15

    Protein-lipid films based on the enzyme alkaline phosphatase were subjected to the action of chelating drugs, which are used for accelerating the removal of heavy metals from the human body, and the elemental composition of the resulting films was investigated. Total-reflection X-ray fluorescence measurements were performed at the Berlin Electron Storage Ring Company for Synchrotron Radiation (BESSY) in Germany. A comparative estimation of the protective effect of four drugs (EDTA, succimer, xydiphone, and mediphon) on membrane-bound enzymes damaged by lead ions was made. The changes in the elemental composition of the protein-lipid films caused by high doses of chelating drugs were investigated. It was shown that state-of-the-art X-ray techniques can, in principle, be used to develop new methods for the in vitro evaluation of the efficiency of drugs, providing differential data on their actions.

  9. Spectral and molecular modeling investigations of supramolecular complexes of mefenamic acid and aceclofenac with α- and β-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Siva, S.; Kothai Nayaki, S.; Rajendiran, N.

    2017-03-01

    Inclusion complexes of mefenamic acid (MFA) and aceclofenac (ALF) with α- and β-cyclodextrins (CDs) in aqueous medium were investigated by absorption, fluorescence, time-resolved fluorescence methods. The solid inclusion complexes between drugs and CDs were characterized by SEM, TEM, FT-IR, 1H NMR, DSC and powder XRD techniques. Spectral studies indicated that both CDs form 1:1 inclusion complex with MFA and ALF. The experimental results revealed that the inclusion process is a spontaneous process. Time-resolved fluorescence studies suggested that ALF exhibited biexponential decay in aqueous and triexponential decay in CD whereas significant enhancement of lifetime of decay components of MFA was observed. Morphologies of drug-CD complexes observed by TEM demonstrate that self-aggregates of MFA/α-CD, ALF/α-CD and ALF/β-CD were nano-sized particles while vesicles were observed for MFA/β-CD. A spatial arrangement of inclusion complex is proposed based on 1H NMR and PM3 results. Investigations of thermodynamic and electronic properties confirmed the stability of the inclusion complex.

  10. Molecular Contamination Investigation Facility (MCIF) Capabilities

    NASA Technical Reports Server (NTRS)

    Soules, David M.

    2013-01-01

    This facility was used to guide the development of ASTM E 1559 center dot Multiple Quartz Crystal Microbalances (QCMs), large sample and spectral effects capability center dot Several instrumented, high vacuum chamber systems are used to evaluate the molecular outgassing characteristics of materials, flight components and other sensitive surfaces. Test materials for spacecraft/instrument selection center.Test flight components for acceptable molecular outgas levels center dot Determine time/temperature vacuum bake-out requirements center. Data used to set limits for use of materials and specific components center. Provide Input Data to Contamination Transport Models -Applied to numerous flight projects over the past 20 years.

  11. Molecular genetic investigations of root gravitropism and other complex growth behaviors using Arabidopsis and Brachypodium as models

    NASA Astrophysics Data System (ADS)

    Masson, Patrick; Barker, Richard; Miller, Nathan; Su, Shih-Hao; Su, Shih-Heng

    2016-07-01

    downward on vertical surfaces, or fully embedded in agar-containing medium. Brachypodium distachyon accessions differ in their gravisensitivity, kinetics of gravitropism and occurrence, periodicity and amplitude of tip oscillations. Mathematical models are being built to fit the data, and used to estimate growth, gravitropism and oscillation parameters for incorporation into Genome-Wide Association Study (GWAS) algorithms aimed at identifying contributing loci. This work was supported by grants from the National Aeronautics and Space Administration (NASA) and from the National Science Foundation (NSF).

  12. Assessment of Molecular Modeling & Simulation

    SciTech Connect

    2002-01-03

    This report reviews the development and applications of molecular and materials modeling in Europe and Japan in comparison to those in the United States. Topics covered include computational quantum chemistry, molecular simulations by molecular dynamics and Monte Carlo methods, mesoscale modeling of material domains, molecular-structure/macroscale property correlations like QSARs and QSPRs, and related information technologies like informatics and special-purpose molecular-modeling computers. The panel's findings include the following: The United States leads this field in many scientific areas. However, Canada has particular strengths in DFT methods and homogeneous catalysis; Europe in heterogeneous catalysis, mesoscale, and materials modeling; and Japan in materials modeling and special-purpose computing. Major government-industry initiatives are underway in Europe and Japan, notably in multi-scale materials modeling and in development of chemistry-capable ab-initio molecular dynamics codes.

  13. Molecular modelling and molecular dynamics of CFTR.

    PubMed

    Callebaut, Isabelle; Hoffmann, Brice; Lehn, Pierre; Mornon, Jean-Paul

    2017-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a member of the ATP-binding cassette (ABC) transporter superfamily that functions as an ATP-gated channel. Considerable progress has been made over the last years in the understanding of the molecular basis of the CFTR functions, as well as dysfunctions causing the common genetic disease cystic fibrosis (CF). This review provides a global overview of the theoretical studies that have been performed so far, especially molecular modelling and molecular dynamics (MD) simulations. A special emphasis is placed on the CFTR-specific evolution of an ABC transporter framework towards a channel function, as well as on the understanding of the effects of disease-causing mutations and their specific modulation. This in silico work should help structure-based drug discovery and design, with a view to develop CFTR-specific pharmacotherapeutic approaches for the treatment of CF in the context of precision medicine.

  14. Molecular modeling of polynucleotide complexes.

    PubMed

    Meneksedag-Erol, Deniz; Tang, Tian; Uludağ, Hasan

    2014-08-01

    , the critical aspects of gene therapy are expected to be better investigated and direct comparison between more realistic molecular modeling and experiments may open the path for design of next generation gene therapeutics.

  15. A combination of hand-held models and computer imaging programs helps students answer oral questions about molecular structure and function: a controlled investigation of student learning.

    PubMed

    Harris, Michelle A; Peck, Ronald F; Colton, Shannon; Morris, Jennifer; Chaibub Neto, Elias; Kallio, Julie

    2009-01-01

    We conducted a controlled investigation to examine whether a combination of computer imagery and tactile tools helps introductory cell biology laboratory undergraduate students better learn about protein structure/function relationships as compared with computer imagery alone. In all five laboratory sections, students used the molecular imaging program, Protein Explorer (PE). In the three experimental sections, three-dimensional physical models were made available to the students, in addition to PE. Student learning was assessed via oral and written research summaries and videotaped interviews. Differences between the experimental and control group students were not found in our typical course assessments such as research papers, but rather were revealed during one-on-one interviews with students at the end of the semester. A subset of students in the experimental group produced superior answers to some higher-order interview questions as compared with students in the control group. During the interview, students in both groups preferred to use either the hand-held models alone or in combination with the PE imaging program. Students typically did not use any tools when answering knowledge (lower-level thinking) questions, but when challenged with higher-level thinking questions, students in both the control and experimental groups elected to use the models.

  16. A Combination of Hand-Held Models and Computer Imaging Programs Helps Students Answer Oral Questions about Molecular Structure and Function: A Controlled Investigation of Student Learning

    ERIC Educational Resources Information Center

    Harris, Michelle A.; Peck, Ronald F.; Colton, Shannon; Morris, Jennifer; Neto, Elias Chaibub; Kallio, Julie

    2009-01-01

    We conducted a controlled investigation to examine whether a combination of computer imagery and tactile tools helps introductory cell biology laboratory undergraduate students better learn about protein structure/function relationships as compared with computer imagery alone. In all five laboratory sections, students used the molecular imaging…

  17. Homology modeling, molecular docking and MD simulation studies to investigate role of cysteine protease from Xanthomonas campestris in degradation of Aβ peptide.

    PubMed

    Dhanavade, Maruti J; Jalkute, Chidambar B; Barage, Sagar H; Sonawane, Kailas D

    2013-12-01

    Cysteine protease is known to degrade amyloid beta peptide which is a causative agent of Alzheimer's disease. This cleavage mechanism has not been studied in detail at the atomic level. Hence, a three-dimensional structure of cysteine protease from Xanthomonas campestris was constructed by homology modeling using Geno3D, SWISS-MODEL, and MODELLER 9v7. All the predicted models were analyzed by PROCHECK and PROSA. Three-dimensional model of cysteine protease built by MODELLER 9v7 shows similarity with human cathepsin B crystal structure. This model was then used further for docking and simulation studies. The molecular docking study revealed that Cys17, His87, and Gln88 residues of cysteine protease form an active site pocket similar to human cathepsin B. Then the docked complex was refined by molecular dynamic simulation to confirm its stable behavior over the entire simulation period. The molecular docking and MD simulation studies showed that the sulfhydryl hydrogen atom of Cys17 of cysteine protease interacts with carboxylic oxygen of Lys16 of Aβ peptide indicating the cleavage site. Thus, the cysteine protease model from X. campestris having similarity with human cathepsin B crystal structure may be used as an alternate approach to cleave Aβ peptide a causative agent of Alzheimer's disease.

  18. Investigating Microvibration Sources Modelling

    NASA Astrophysics Data System (ADS)

    Addari, Daniele; Aglietti, Guglielmo S.; Remedia, Marcello

    2014-06-01

    One of the challenges related to microvibration is investigating the characterisation of the microvibration sources (here emphasis is given to reaction wheel assemblies) on board satellites. This usually involves series of experiments to characterise the hardware and produce representative models. Here we present a methodology that gives good estimates covering a wide frequency range and reduce the complexity of the test campaign.In addition, a practical example of coupling between a reaction wheel assembly and a structural panel where the coupled loads have been estimated using the mathematical model and compared with experimental test results (retrieved using an interface load transducer) will be presented, giving indications of the level of accuracy that can be expected from this type of analyses.

  19. Abstract models of molecular walkers

    NASA Astrophysics Data System (ADS)

    Semenov, Oleg

    Recent advances in single-molecule chemistry have led to designs for artificial multi-pedal walkers that follow tracks of chemicals. The walkers, called molecular spiders, consist of a rigid chemically inert body and several flexible enzymatic legs. The legs can reversibly bind to chemical substrates on a surface, and through their enzymatic action convert them to products. We study abstract models of molecular spiders to evaluate how efficiently they can perform two tasks: molecular transport of cargo over tracks and search for targets on finite surfaces. For the single-spider model our simulations show a transient behavior wherein certain spiders move superdiffusively over significant distances and times. This gives the spiders potential as a faster-than-diffusion transport mechanism. However, analysis shows that single-spider motion eventually decays into an ordinary diffusive motion, owing to the ever increasing size of the region of products. Inspired by cooperative behavior of natural molecular walkers, we propose a symmetric exclusion process (SEP) model for multiple walkers interacting as they move over a one-dimensional lattice. We show that when walkers are sequentially released from the origin, the collective effect is to prevent the leading walkers from moving too far backwards. Hence, there is an effective outward pressure on the leading walkers that keeps them moving superdiffusively for longer times. Despite this improvement the leading spider eventually slows down and moves diffusively, similarly to a single spider. The slowdown happens because all spiders behind the leading spiders never encounter substrates, and thus they are never biased. They cannot keep up with leading spiders, and cannot put enough pressure on them. Next, we investigate search properties of a single and multiple spiders moving over one- and two-dimensional surfaces with various absorbing and reflecting boundaries. For the single-spider model we evaluate by how much the

  20. Molecular Motors and Stochastic Models

    NASA Astrophysics Data System (ADS)

    Lipowsky, Reinhard

    The behavior of single molecular motors such as kinesin or myosin V, which move on linear filaments, involves a nontrivial coupling between the biochemical motor cycle and the stochastic movement. This coupling can be studied in the framework of nonuniform ratchet models which are characterized by spatially localized transition rates between the different internal states of the motor. These models can be classified according to their functional relationships between the motor velocity and the concentration of the fuel molecules. The simplest such relationship applies to two subclasses of models for dimeric kinesin and agrees with experimental observations on this molecular motor.

  1. The role of the deformational entropy in the miscibility of polymer blends investigated using a hybrid statistical mechanics and molecular dynamics model.

    PubMed

    Madkour, Tarek M; Salem, Sarah A; Miller, Stephen A

    2013-04-28

    To fully understand the thermodynamic nature of polymer blends and accurately predict their miscibility on a microscopic level, a hybrid model employing both statistical mechanics and molecular dynamics techniques was developed to effectively predict the total free energy of mixing. The statistical mechanics principles were used to derive an expression for the deformational entropy of the chains in the polymeric blends that could be evaluated from molecular dynamics trajectories. Evaluation of the entropy loss due to the deformation of the polymer chains in the case of coiling as a result of the repulsive interactions between the blend components or in the case of swelling due to the attractive interactions between the polymeric segments predicted a negative value for the deformational entropy resulting in a decrease in the overall entropy change upon mixing. Molecular dynamics methods were then used to evaluate the enthalpy of mixing, entropy of mixing, the loss in entropy due to the deformation of the polymeric chains upon mixing and the total free energy change for a series of polar and non-polar, poly(glycolic acid), PGA, polymer blends.

  2. Molecular Modeling of Thermosetting Polymers

    NASA Astrophysics Data System (ADS)

    Patnaik, Soumya; Varshney, Vikas; Farmer, Barry

    2008-03-01

    In this work we present molecular modeling of thermosetting polymers with special emphasis on building atomistic models. Different approaches to building highly cross-linked polymer networks starting from un-crosslinked systems are discussed. A multi-step procedure for relaxing the molecular topology during crosslinking was proposed which allows for minimizing the increase in the residual internal stresses with increasing degree of crosslinking. This methodology was applied to epoxy based thermosets and several materials properties such as density, Young's modulus, glass transition temperature, thermal expansion coefficient and volume shrinkage during curing were calculated and found to be in good agreement with experimental results. Along with the materials properties, the simulations also highlighted the distribution of molecular weight build up and inception of gel point during the network formation.

  3. Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0399 TITLE: Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy PRINCIPAL INVESTIGATOR: John F...Include area code) October 2015 Annual Report 30 Sep 2014 - 29 Sep 2015 Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy John...encephalopathy (CTE), but the underlying molecular changes remain unclear. Here, biochemical and genetic studies that deepen our understanding of the

  4. Model Pores of Molecular Dimension

    PubMed Central

    Quinn, J. A.; Anderson, J. L.; Ho, W. S.; Petzny, W. J.

    1972-01-01

    Extremely uniform pores of near molecular dimension can be formed by the irradiation-etching technique first demonstrated by Price and Walker. The technique has now been developed to the stage where it can be used to fabricate model membranes for examining the various steric, hydrodynamic, and electrodynamic phenomena encountered in transport through molecular-size pores. Methods for preparing and characterizing membranes with pores as small as 25 A (radius) are described in this paper. Results on pore size determination via Knudsen gas flow and electrolyte conduction are compared. Pore wall modification by monolayer deposition is also discussed. PMID:4339801

  5. Interaction of vitamin B1 with bovine serum albumin investigation using vitamin B1-selective electrode: potentiometric and molecular modeling study.

    PubMed

    Hosseinzadeh, Reza; Khorsandi, Khatereh

    2016-09-01

    Vitamin B1 or thiamin is one of the B vitamins. All B vitamins help the body to convert food (carbohydrates) into fuel (glucose), which produces energy. The B vitamins are necessary for healthy skin, eyes, hair, and liver. It also could help the nervous system function properly, and is necessary for brain functions. Drug interactions with protein can affect the distribution of the drug and eliminate the drug in living systems. In this study, the binding of thiamine hydrochloride (vitamin B1) to bovine serum albumin (BSA) was evaluated using a new proposed vitamin B1 (thiamine)-selective membrane electrode under various experimental conditions, such as pH, ionic strength, and protein concentration; in addition molecular modeling was applied as well. The binding isotherms plotted based on potentiometric data and analyzed using the Wyman binding potential concept. The apparent binding constant was determined and used for the calculation of intrinsic Gibbs free energy of binding. According to the electrochemical and molecular docking results, it can be concluded that the hydrophobic interactions and hydrogen binding are major interactions between BSA and vitamin B1.

  6. Molecular model for chirality phenomena.

    PubMed

    Latinwo, Folarin; Stillinger, Frank H; Debenedetti, Pablo G

    2016-10-21

    Chirality is a hallmark feature for molecular recognition in biology and chemical physics. We present a three-dimensional continuum model for studying chirality phenomena in condensed phases using molecular simulations. Our model system is based upon a simple four-site molecule and incorporates non-trivial kinetic behavior, including the ability to switch chirality or racemize, as well as thermodynamics arising from an energetic preference for specific chiral interactions. In particular, we introduce a chiral renormalization parameter that can locally favor either homochiral or heterochiral configurations. Using this model, we explore a range of chirality-specific phenomena, including the kinetics of chiral inversion, the mechanism of spontaneous chiral symmetry breaking in the liquid, chirally driven liquid-liquid phase separation, and chiral crystal structures.

  7. Molecular Modeling of Cardiac Troponin

    NASA Astrophysics Data System (ADS)

    Manning, Edward P.

    The cardiac thin filament regulates interactions of actin and myosin, the force-generating elements of muscular contraction. Over the past several decades many details have been discovered regarding the structure and function of the cardiac thin filament and its components, including cardiac troponin (cTn). My hypothesis is that signal propagation occurs between distant ends of the cardiac troponin complex through calcium-dependent alterations in the dynamics of cTn and tropomyosin (Tm). I propose a model of the thin filament that encompasses known structures of cTn, Tm and actin to gain insight into cardiac troponin's allosteric regulation of thin filament dynamics. By performing molecular dynamics simulations of cTn in conjunction with overlapping Tm in two conditions, with and without calcium bound to site II of cardiac troponin C (cTnC), I found a combination of calcium-dependent changes in secondary structure and dynamics throughout the cTn-Tm complex. I then applied this model to investigate familial hypertrophic cardiomyopathy (FHC), a disease of the sarcomere that is one of the most commonly occurring genetic causes of heart disease. Approximately 15% of known FHC-related mutations are found in cardiac troponin T (cTnT), most of which are in or flank the alpha-helical N-tail domain TNT1. TNT1 directly interacts with overlapping Tm coiled coils. Using this model I identified effects of TNT1 mutations that propagate to the cTn core where site II of cTnC, the regulatory site of calcium binding in the thin filament, is located. Specifically, I found that mutations in TNT1 alter the flexibility of TNT1 and that the flexibility of TNT1 is inversely proportional to the cooperativity of calcium activation of the thin filament. Further, I identified a pathway of propagation of structural and dynamic changes linking TNT1 to site II of cTnC. Mutation-induced changes at site II cTnC alter calcium coordination which corresponds to biophysical measurements of calcium

  8. Molecular modeling of heterogeneous catalysis

    NASA Astrophysics Data System (ADS)

    Gislason, Jason Joseph

    A novel method for modeling heterogeneous catalysis was developed to further facilitate the understanding of catalytic reactor mechanisms. The method employs molecular dynamics simulations, statistical mechanical, and Unity Bond Index - Quadratic Exponential Potential (UBI-QEP) calculations to calculate the rate constants for reactions on metal surfaces. The primary difficulty of molecular dynamics simulations on metal surfaces has been the lack of reliable reactive potential energy surfaces. We have overcome this through the development of the Normalized Bond Index - Reactive Potential Function (NBI-RPF), which can accurately describe the reaction of adsorbates on metal surfaces. The first calculations of rate constants for a reaction on a metal surface using molecular dynamics simulations are presented. This method is applied to the determination of the mechanism for selective hydrogenation of acetylene in an ethylene rich flow. It was determined that the selectivity for acetylene hydrogenation is attributable to the higher reactivity of acetylene versus ethylene with respect to hydrogenation by molecular hydrogen. It was shown that hydrogen transfer from the carbonaceous layer to acetylene or ethylene is insignificant in the hydrogenation process. Molecular dynamics simulations and molecular mechanics calculations were used to determine the diffusion rate constants for dimethylnaphthalene isomers is mordenite. 2,6-dimethylnaphthalene and 2,7-dimethylnaphthalene were found to have similar diffusion rate constants. Grand canonical Monte Carlo calculations were performed on the competitive adsorption of 2,6-dimethylnaphthalene and 2,7-dimethylnaphthalene in type X zeolites exchanged individually with barium, calcium, potassium, and rubidium ions, calcium exchanged MCM-22, and hydrogen form mordenite (MOR), X zeolite, Y zeolite, hypBEB, ZSM- 12, and MCM-22. These calculations showed that barium exchanged X zeolite was the most selective toward 2

  9. Ubiquitin: molecular modeling and simulations.

    PubMed

    Ganoth, Assaf; Tsfadia, Yossi; Wiener, Reuven

    2013-11-01

    The synthesis and destruction of proteins are imperative for maintaining their cellular homeostasis. In the 1970s, Aaron Ciechanover, Avram Hershko, and Irwin Rose discovered that certain proteins are tagged by ubiquitin before degradation, a discovery that awarded them the 2004 Nobel Prize in Chemistry. Compelling data gathered during the last several decades show that ubiquitin plays a vital role not only in protein degradation but also in many cellular functions including DNA repair processes, cell cycle regulation, cell growth, immune system functionality, hormone-mediated signaling in plants, vesicular trafficking pathways, regulation of histone modification and viral budding. Due to the involvement of ubiquitin in such a large number of diverse cellular processes, flaws and impairments in the ubiquitin system were found to be linked to cancer, neurodegenerative diseases, genetic disorders, and immunological disorders. Hence, deciphering the dynamics and complexity of the ubiquitin system is of significant importance. In addition to experimental techniques, computational methodologies have been gaining increasing influence in protein research and are used to uncover the structure, stability, folding, mechanism of action and interactions of proteins. Notably, molecular modeling and molecular dynamics simulations have become powerful tools that bridge the gap between structure and function while providing dynamic insights and illustrating essential mechanistic characteristics. In this study, we present an overview of molecular modeling and simulations of ubiquitin and the ubiquitin system, evaluate the status of the field, and offer our perspective on future progress in this area of research.

  10. Optical models of the molecular atmosphere

    NASA Technical Reports Server (NTRS)

    Zuev, V. E.; Makushkin, Y. S.; Mitsel, A. A.; Ponomarev, Y. N.; Rudenko, V. P.; Firsov, K. M.

    1986-01-01

    The use of optical and laser methods for performing atmospheric investigations has stimulated the development of the optical models of the atmosphere. The principles of constructing the optical models of molecular atmosphere for radiation with different spectral composition (wideband, narrowband, and monochromatic) are considered in the case of linear and nonlinear absorptions. The example of the development of a system which provides for the modeling of the processes of optical-wave energy transfer in the atmosphere is presented. Its physical foundations, structure, programming software, and functioning were considered.

  11. A dynamic structural model of expanded RNA CAG repeats: a refined X-ray structure and computational investigations using molecular dynamics and umbrella sampling simulations.

    PubMed

    Yildirim, Ilyas; Park, HaJeung; Disney, Matthew D; Schatz, George C

    2013-03-06

    One class of functionally important RNA is repeating transcripts that cause disease through various mechanisms. For example, expanded CAG repeats can cause Huntington's and other disease through translation of toxic proteins. Herein, a crystal structure of r[5'UUGGGC(CAG)3GUCC]2, a model of CAG expanded transcripts, refined to 1.65 Å resolution is disclosed that shows both anti-anti and syn-anti orientations for 1 × 1 nucleotide AA internal loops. Molecular dynamics (MD) simulations using AMBER force field in explicit solvent were run for over 500 ns on the model systems r(5'GCGCAGCGC)2 (MS1) and r(5'CCGCAGCGG)2 (MS2). In these MD simulations, both anti-anti and syn-anti AA base pairs appear to be stable. While anti-anti AA base pairs were dynamic and sampled multiple anti-anti conformations, no syn-anti ↔ anti-anti transformations were observed. Umbrella sampling simulations were run on MS2, and a 2D free energy surface was created to extract transformation pathways. In addition, an explicit solvent MD simulation over 800 ns was run on r[5'GGGC(CAG)3GUCC]2, which closely represents the refined crystal structure. One of the terminal AA base pairs (syn-anti conformation), transformed to anti-anti conformation. The pathway followed in this transformation was the one predicted by umbrella sampling simulations. Further analysis showed a binding pocket near AA base pairs in syn-anti conformations. Computational results combined with the refined crystal structure show that global minimum conformation of 1 × 1 nucleotide AA internal loops in r(CAG) repeats is anti-anti but can adopt syn-anti depending on the environment. These results are important to understand RNA dynamic-function relationships and to develop small molecules that target RNA dynamic ensembles.

  12. A dynamic structural model of expanded RNA CAG repeats: A refined X-ray structure and computational investigations using molecular dynamics and umbrella sampling simulations

    PubMed Central

    Yildirim, Ilyas; Park, Hajeung; Disney, Matthew D.; Schatz, George C.

    2013-01-01

    One class of functionally important RNA is repeating transcripts that cause disease through various mechanisms. For example, expanded r(CAG) repeats can cause Huntington’s and other disease through translation of toxic proteins. Herein, crystal structure of r[5ʹUUGGGC(CAG)3GUCC]2, a model of CAG expanded transcripts, refined to 1.65 Å resolution is disclosed that show both anti-anti and syn-anti orientations for 1×1 nucleotide AA internal loops. Molecular dynamics (MD) simulations using Amber force field in explicit solvent were run for over 500 ns on model systems r(5ʹGCGCAGCGC)2 (MS1) and r(5ʹCCGCAGCGG)2 (MS2). In these MD simulations, both anti-anti and syn-anti AA base pairs appear to be stable. While anti-anti AA base pairs were dynamic and sampled multiple anti-anti conformations, no syn-anti↔anti-anti transformations were observed. Umbrella sampling simulations were run on MS2, and a 2D free energy surface was created to extract transformation pathways. In addition, over 800 ns explicit solvent MD simulation was run on r[5ʹGGGC(CAG)3GUCC]2, which closely represents the refined crystal structure. One of the terminal AA base pairs (syn-anti conformation), transformed to anti-anti conformation. The pathway followed in this transformation was the one predicted by umbrella sampling simulations. Further analysis showed a binding pocket near AA base pairs in syn-anti conformations. Computational results combined with the refined crystal structure show that global minimum conformation of 1×1 nucleotide AA internal loops in r(CAG) repeats is anti-anti but can adopt syn-anti depending on the environment. These results are important to understand RNA dynamic-function relationships and develop small molecules that target RNA dynamic ensembles. PMID:23441937

  13. Extending students' practice of metacognitive regulation strategies in the undergraduate chemistry laboratory and investigation of Pb2+ binding to calmodulin with circular dichroism and molecular dynamics modeling

    NASA Astrophysics Data System (ADS)

    Valencia Navarro, Laura N.

    The following dissertation was composed of two projects in chemistry education and benchwork/computational biochemistry. The chemistry education research explored students' practice of metacognitive strategies while solving open-ended laboratory problems when engaged in an instructional environment, the Science Writing Heuristic (SWH), that was characterized as supporting metacognitive regulation strategy use. Through in-depth interviews with students, results demonstrated that students in the SWH environment, compared to non-SWH students, used metacognitive strategies to a greater degree and to a greater depth when solving open-ended laboratory problems. As students engaged in higher levels of metacognitive regulation, their elective use of peers became a prominent path for supporting the practice of metacognitive strategies. Students claimed that the structure of the SWH weekly laboratory experiments improved their ability to solve open-ended lab problems. This research not only provided a lens into students' descriptions of their regulation strategy practices in the laboratory, but it also supported that the way that a laboratory environment is arranged can affect these regulation strategy practices and their transfer to new situations. In the biochemical study on the binding of Pb2+ to calmodulin (CaM), data was acquired via circular dichroism (CD) and molecular dynamics modeling. CD signal data indicated a unique signal from Pb-CaM and a significantly smaller ratio theta208/theta222 for Pb-CaM than Ca-CaM. An analysis of secondary structure content indicated that alpha-helical structure decreased and random coil structure increased when CaM was saturated with Pb2+ compared to Ca2+ saturated CaM. A molecular dynamics simulation of Pb2+ binding to CaM showed that Pb2+ ions bound to sites outside of the known canonical binding sites including the linker region, and indicated change in secondary structure. These results support the theory of opportunistic binding

  14. Creep rupture of fiber bundles: A molecular dynamics investigation

    NASA Astrophysics Data System (ADS)

    Linga, G.; Ballone, P.; Hansen, Alex

    2015-08-01

    The creep deformation and eventual breaking of polymeric samples under a constant tensile load F is investigated by molecular dynamics based on a particle representation of the fiber bundle model. The results of the virtual testing of fibrous samples consisting of 40 000 particles arranged on Nc=400 chains reproduce characteristic stages seen in the experimental investigations of creep in polymeric materials. A logarithmic plot of the bundle lifetime τ versus load F displays a marked curvature, ruling out a simple power-law dependence of τ on F . A power law τ ˜F-4 , however, is recovered at high load. We discuss the role of reversible bond breaking and formation on the eventual fate of the sample and simulate a different type of creep testing, imposing a constant stress rate on the sample up to its breaking point. Our simulations, relying on a coarse-grained representation of the polymer structure, introduce new features into the standard fiber bundle model, such as real-time dynamics, inertia, and entropy, and open the way to more detailed models, aiming at material science aspects of polymeric fibers, investigated within a sound statistical mechanics framework.

  15. Investigation of a calcium-responsive contrast agent in cellular model systems: feasibility for use as a smart molecular probe in functional MRI.

    PubMed

    Angelovski, Goran; Gottschalk, Sven; Milošević, Milena; Engelmann, Jörn; Hagberg, Gisela E; Kadjane, Pascal; Andjus, Pavle; Logothetis, Nikos K

    2014-05-21

    Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca(2+) may allow tracking neuronal activity independent of brain vasculature, thus avoiding the characteristic limitations of current fMRI techniques. Here we report an in vitro proof-of-principle study with a Ca(2+)-sensitive, Gd(3+)-based SCA in an attempt to validate its potential use as a functional in vivo marker. First, we quantified its relaxometric response in a complex 3D cell culture model. Subsequently, we examined potential changes in the functionality of primary glial cells following administration of this SCA. Monitoring intracellular Ca(2+) showed that, despite a reduction in the Ca(2+) level, transport of Ca(2+) through the plasma membrane remained unaffected, while stimulation with ATP induced Ca(2+)-transients suggested normal cellular signaling in the presence of low millimolar SCA concentrations. SCAs merely lowered the intracellular Ca(2+) level. Finally, we estimated the longitudinal relaxation times (T1) for an idealized in vivo fMRI experiment with SCA, for extracellular Ca(2+) concentration level changes expected during intense neuronal activity which takes place upon repetitive stimulation. The values we obtained indicate changes in T1 of around 1-6%, sufficient to be robustly detectable using modern MRI methods in high field scanners. Our results encourage further attempts to develop even more potent SCAs and appropriate fMRI protocols. This would result in novel methods that allow monitoring of essential physiological processes at the cellular and molecular level.

  16. Molecular Tools for Investigating the Gut Microbiota

    NASA Astrophysics Data System (ADS)

    Lay, Christophe

    The “microbial world within us” (Zoetendal et al., 2006) is populated by a complex society of indigenous microorganisms that feature different “ethnic” populations. Those microbial cells thriving within us are estimated to outnumber human body cells by a factor of ten to one. Insights into the relation between the intestinal microbial community and its host have been gained through gnotobiology. Indeed, the influence of the gut microbiota upon human development, physiology, immunity, and nutrition has been inferred by comparing gnotoxenic and axenic murine models (Hooper et al., 1998, 2002, 2003; Hooper and Gordon, 2001).

  17. Molecular contamination modeling with CTSP

    NASA Astrophysics Data System (ADS)

    Brieda, Lubos

    2016-11-01

    Spacecraft instruments and thermal control surfaces are generally highly sensitive to molecular and particulate contamination. Despite best efforts taken during assembly, integration, and test, it is impossible to completely eliminate all sources of contaminants. Contamination transport analysis then becomes of critical importance. It can be used to predict the end of life accumulation on critical surfaces from prescribed source rates. Conversely, given allowable deposition levels, contamination modeling can be used to determine the cleanliness requirements to be met prior to launch. This paper describes a recently developed code for modeling contamination transport. Unlike other tools used by the community, CTSP concurrently traces many simulation particles through small time steps. This allows the code to visualize contaminant partial pressures, and to also include aerodynamic, gravitation, or electrostatic forces. The code is demonstrated by simulating an outgassing characterization test in a bell jar.

  18. Theoretical investigation of the molecular structure of the isoquercitrin molecule

    NASA Astrophysics Data System (ADS)

    Cornard, J. P.; Boudet, A. C.; Merlin, J. C.

    1999-09-01

    Isoquercitrin is a glycosilated flavonoid that has received a great deal of attention because of its numerous biological effects. We present a theoretical study on isoquercitrin using both empirical (Molecular Mechanics (MM), with MMX force field) and quantum chemical (AM1 semiempirical method) techniques. The most stable structures of the molecule obtained by MM calculations have been used as input data for the semiempirical treatment. The position and orientation of the glucose moiety with regard to the remainder of the molecule have been investigated. The flexibility of isoquercitrin principally lies in rotations around the inter-ring bond and the sugar link. In order to know the structural modifications generated by the substitution by a sugar, geometrical parameters of quercetin (aglycon) and isoquercitrin have been compared. The good accordance between theoretical and experimental electronic spectra permits to confirm the reliability of the structural model.

  19. Thermal and molecular investigation of laser tissue welding

    SciTech Connect

    Small, W., IV

    1998-06-01

    Despite the growing number of successful animal and human trials, the exact mechanisms of laser tissue welding remain unknown. Furthermore, the effects of laser heating on tissue on the molecular scale are not fully understood. To address these issues, a multi-front attack oil both extrinsic (solder/patch mediated) and intrinsic (laser only) tissue welding was launched using two-color infrared thermometry, computer modeling, weld strength assessment, biochemical assays, and vibrational spectroscopy. The coupling of experimentally measured surface temperatures with the predictive numerical simulations provided insight into the sub-surface dynamics of the laser tissue welding process. Quantification of the acute strength of the welds following the welding procedure enabled comparison among trials during an experiment, with previous experiments, and with other studies in the literature. The acute weld integrity also provided an indication of tile probability of long-term success. Molecular effects induced In the tissue by laser irradiation were investigated by measuring tile concentrations of specific collagen covalent crosslinks and characterizing the Fourier-Transform infrared (FTIR) spectra before and after the laser exposure.

  20. Model of evolution of molecular sequences

    NASA Astrophysics Data System (ADS)

    Luo, Liaofu; Tsai, Lu; Lee, Weijiang

    1990-05-01

    A simplified model of the evolution of molecular sequences is proposed. An ensemble of strings is considered that consists of two letters and undergoes random point mutations and natural selections. A set of evolution equations is deduced. From the solution it is found that the first-order (second-order) informational parameters (redundancies) D1 decrease (D2 increase) in the course of evolution. Furthermore, the statistical correlations of the letters (bases) in the sequences are investigated in detail and the short-distance correlation is demonstrated. These results give a preliminary explanation of some physical aspects in the evolution of nucleic acid sequences.

  1. 3D Printing of Molecular Models

    ERIC Educational Resources Information Center

    Gardner, Adam; Olson, Arthur

    2016-01-01

    Physical molecular models have played a valuable role in our understanding of the invisible nano-scale world. We discuss 3D printing and its use in producing models of the molecules of life. Complex biomolecular models, produced from 3D printed parts, can demonstrate characteristics of molecular structure and function, such as viral self-assembly,…

  2. Spectroscopic, biological, and molecular modeling studies on the interactions of [Fe(III)-meloxicam] with G-quadruplex DNA and investigation of its release from bovine serum albumin (BSA) nanoparticles.

    PubMed

    Ebrahimi, Malihe; Khayamian, Taghi; Hadadzadeh, Hassan; Sayed Tabatabaei, Badraldin Ebrahim; Jannesari, Zahra; Khaksar, Ghazale

    2015-01-01

    The guanine-rich sequence, specifically in DNA, telomeric DNA, is a potential target of anticancer drugs. In this work, a mononuclear Fe(III) complex containing two meloxicam ligands was synthesized as a G-quadruplex stabilizer. The interaction between the Fe(III) complex and G-quadruplex with sequence of 5'-G3(T2AG3)3-3' (HTG21) was investigated using spectroscopic methods, molecular modeling, and polymerase chain reaction (PCR) assays. The spectroscopic methods of UV-vis, fluorescence, and circular dichroism showed that the metal complex can effectively induce and stabilize G-quadruplex structure in the G-rich 21-mer sequence. Also, the binding constant between the Fe(III) complex and G-quadruplex was measured by these methods and it was found to be 4.53(±0.30) × 10(5) M(-1)). The PCR stop assay indicated that the Fe(III) complex inhibits DNA amplification. The cell viability assay showed that the complex has significant antitumor activities against Hela cells. According to the UV-vis results, the interaction of the Fe(III) complex with duplex DNA is an order of magnitude lower than G-quadruplex. Furthermore, the release of the complex incorporated in bovine serum albumin nanoparticles was also investigated in physiological conditions. The release of the complex followed a bi-phasic release pattern with high and low releasing rates at the first and second phases, respectively. Also, in order to obtain the binding mode of the Fe(III) complex with G-quadruplex, molecular modeling was performed. The molecular docking results showed that the Fe(III) complex was docked to the end-stacked of the G-quadruplex with a π-π interaction, created between the meloxicam ligand and the guanine bases of the G-quadruplex.

  3. Investigation of Ribosomes Using Molecular Dynamics Simulation Methods.

    PubMed

    Makarov, G I; Makarova, T M; Sumbatyan, N V; Bogdanov, A A

    2016-12-01

    The ribosome as a complex molecular machine undergoes significant conformational changes while synthesizing a protein molecule. Molecular dynamics simulations have been used as complementary approaches to X-ray crystallography and cryoelectron microscopy, as well as biochemical methods, to answer many questions that modern structural methods leave unsolved. In this review, we demonstrate that all-atom modeling of ribosome molecular dynamics is particularly useful in describing the process of tRNA translocation, atomic details of behavior of nascent peptides, antibiotics, and other small molecules in the ribosomal tunnel, and the putative mechanism of allosteric signal transmission to functional sites of the ribosome.

  4. Molecular models for actinide speciation

    SciTech Connect

    Clark, D.L.; Watkin, J.G.; Morris, D.E.; Berg, J.M.

    1994-06-01

    Much effort has been devoted to the development of sensitive spectroscopic techniques for the study of actinide speciation based on the sensitivity of f-f electronic absorption bands to oxidation state and ligation of the actinide ions. These efforts assume that data obtained in such studies will be interpretable in terms of changes in complexation of the metal center. However, the current understanding of 5f electronic structure is based on data from solid state doped single crystals. In those studies, the local coordination geometry about the central actinide ion is maintained in an almost perfect high-symmetry environment and will have little relevance for species in solution where deviations from perfect high symmetry tend to be the rule rather than the exception. The authors have developed a vigorous research program in the systematic preparation and spectroscopic characterization of synthetic actinide complexes (Th, U, Np, and Pu) in which they can control nuclearity, oxidation state, and molecular structure. These complexes have been used to determine how observable electronic transitions are perturbed in response to structural changes in the complex in solution. From the spectra obtained for these model complexes, the authors have found that the f-f transitions naturally fall into obvious groupings by coordination number and symmetry by which they can now differentiate between monomeric, dimeric, and trimeric species in solution. The study of radionuclide speciation is fundamentally important to the determination of radionuclide solubility in the groundwater at Yucca Mountain.

  5. Ratchet models of molecular motors

    NASA Astrophysics Data System (ADS)

    Jaster, Nicole

    2003-09-01

    Transport processes in and of cells are of major importance for the survival of the organism. Muscles have to be able to contract, chromosomes have to be moved to opposing ends of the cell during mitosis, and organelles, which are compartments enclosed by membranes, have to be transported along molecular tracks. Molecular motors are proteins whose main task is moving other molecules.For that purpose they transform the chemical energy released in the hydrolysis of ATP into mechanical work. The motors of the cytoskeleton belong to the three super families myosin, kinesin and dynein. Their tracks are filaments of the cytoskeleton, namely actin and the microtubuli. Here, we examine stochastic models which are used for describing the movements of these linear molecular motors. The scale of the movements comprises the regime of single steps of a motor protein up to the directed walk along a filament. A single step bridges around 10 nm, depending on the protein, and takes about 10 ms, if there is enough ATP available. Our models comprise M states or conformations the motor can attain during its movement along a one-dimensional track. At K locations along the track transitions between the states are possible. The velocity of the protein depending on the transition rates between the single states can be determined analytically. We calculate this velocity for systems of up to four states and locations and are able to derive a number of rules which are helpful in estimating the behaviour of an arbitrary given system. Beyond that we have a look at decoupled subsystems, i.e., one or a couple of states which have no connection to the remaining system. With a certain probability a motor undergoes a cycle of conformational changes, with another probability an independent other cycle. Active elements in real transport processes by molecular motors will not be limited to the transitions between the states. In distorted networks or starting from the discrete Master equation of the

  6. Evolution & Phylogenetic Analysis: Classroom Activities for Investigating Molecular & Morphological Concepts

    ERIC Educational Resources Information Center

    Franklin, Wilfred A.

    2010-01-01

    In a flexible multisession laboratory, students investigate concepts of phylogenetic analysis at both the molecular and the morphological level. Students finish by conducting their own analysis on a collection of skeletons representing the major phyla of vertebrates, a collection of primate skulls, or a collection of hominid skulls.

  7. Computerized molecular modeling of carbohydrates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Computerized molecular modleing continues to increase in capability and applicability to carbohydrates. This chapter covers nomenclature and conformational aspects of carbohydrates, perhaps of greater use to carbohydrate-inexperienced computational chemists. Its comments on various methods and studi...

  8. Molecular Sieve Bench Testing and Computer Modeling

    NASA Technical Reports Server (NTRS)

    Mohamadinejad, Habib; DaLee, Robert C.; Blackmon, James B.

    1995-01-01

    The design of an efficient four-bed molecular sieve (4BMS) CO2 removal system for the International Space Station depends on many mission parameters, such as duration, crew size, cost of power, volume, fluid interface properties, etc. A need for space vehicle CO2 removal system models capable of accurately performing extrapolated hardware predictions is inevitable due to the change of the parameters which influences the CO2 removal system capacity. The purpose is to investigate the mathematical techniques required for a model capable of accurate extrapolated performance predictions and to obtain test data required to estimate mass transfer coefficients and verify the computer model. Models have been developed to demonstrate that the finite difference technique can be successfully applied to sorbents and conditions used in spacecraft CO2 removal systems. The nonisothermal, axially dispersed, plug flow model with linear driving force for 5X sorbent and pore diffusion for silica gel are then applied to test data. A more complex model, a non-darcian model (two dimensional), has also been developed for simulation of the test data. This model takes into account the channeling effect on column breakthrough. Four FORTRAN computer programs are presented: a two-dimensional model of flow adsorption/desorption in a packed bed; a one-dimensional model of flow adsorption/desorption in a packed bed; a model of thermal vacuum desorption; and a model of a tri-sectional packed bed with two different sorbent materials. The programs are capable of simulating up to four gas constituents for each process, which can be increased with a few minor changes.

  9. Understanding polycaroboxylate interactions with counterions: A molecular modeling approach

    SciTech Connect

    Fitzwater, S.; Freeman, M.B.

    1993-12-31

    Low molecular weight polycarboyxlates, such as poly(acrylic acid), have utility as dispersants in a variety of commercial applications including home laundry detergents, mineral processing and water treatment. In general, counterions (Ca, Mg, Fe, etc.) are unavoidable in these applications and often dictate the polymer composition and molecular weight necessary for successful performance. The authors have been investigating the interaction of polycarboxylates with counterions in order to better understand how that interaction impacts on the dispersant properties of a polymer. Using computer modeling, it can be seen how molecular geometry, molecular dynamics, and the shape/polarity of the molecular surface are affected by counterion binding and polymer composition. The authors can then combine information from the modeling with experimental information and literature concepts to provide a direction toward the synthesis of improved low molecular weight polycarboxylate dispersants.

  10. Investigation of deformation mechanisms of staggered nanocomposites using molecular dynamics

    NASA Astrophysics Data System (ADS)

    Mathiazhagan, S.; Anup, S.

    2016-08-01

    Biological materials with nanostructure of regularly or stair-wise staggered arrangements of hard platelets reinforced in a soft protein matrix have superior mechanical properties. Applications of these nanostructures to ceramic matrix composites could enhance their toughness. Using molecular dynamics simulations, mechanical behaviour of the bio-inspired nanocomposites is studied. Regularly staggered model shows better flow behaviour compared to stair-wise staggered model due to the symmetrical crack propagation along the interface. Though higher stiffness and strength are obtained for stair-wise staggered models, rapid crack propagation reduces the toughness. Arresting this crack propagation could lead to superior mechanical properties in stair-wise staggered models.

  11. Molecular Modeling of Estrogen Receptor Using Molecular Operating Environment

    ERIC Educational Resources Information Center

    Roy, Urmi; Luck, Linda A.

    2007-01-01

    Molecular modeling is pervasive in the pharmaceutical industry that employs many of our students from Biology, Chemistry and the interdisciplinary majors. To expose our students to this important aspect of their education we have incorporated a set of tutorials in our Biochemistry class. The present article describes one of our tutorials where…

  12. Isotope effects in water as investigated by neutron diffraction and path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Zeidler, Anita; Salmon, Philip S.; Fischer, Henry E.; Neuefeind, Jörg C.; Simonson, J. Mike; Markland, Thomas E.

    2012-07-01

    The structures of heavy and light water at 300 K were investigated by using a joint approach in which the method of neutron diffraction with oxygen isotope substitution was complemented by path integral molecular dynamics simulations. The diffraction results, which give intra-molecular O-D and O-H bond distances of 0.985(5) and 0.990(5) Å, were found to be in best agreement with those obtained by using the flexible anharmonic TTM3-F water model. Both techniques show a difference of ≃ 0.5% between the O-D and O-H intra-molecular bond lengths, and the results support a competing quantum effects model for water in which its structural and dynamical properties are governed by an offset between intra-molecular and inter-molecular quantum contributions. Further consideration of the O-O correlations is needed in order to improve agreement with experiment.

  13. Rheological investigation of highly filled polymers: Effect of molecular weight

    NASA Astrophysics Data System (ADS)

    Hnatkova, Eva; Hausnerova, Berenika; Hales, Andrew; Jiranek, Lukas; Vera, Juan Miguel Alcon

    2015-04-01

    The paper deals with rheological properties of highly filled polymers used in powder injection molding. Within the experimental framework seven PIM feedstocks based on superalloy Inconel 718 powder were prepared. Each feedstock contains the fixed amount of powder loading and the same composition of binder system consisting of three components: polyethylene glycol (PEG) differing in molecular weight, poly (methyl methacrylate) (PMMA) and stearic acid (SA). The aim is to investigate the influence of PEG's molecular weight on the flow properties of feedstocks. Non-Newtonian indices, representing the shear rate sensitivity of the feedstocks, are obtained from a polynomial fit, and found to vary within measured shear rates range from 0.2 to 0.8. Temperature effect is considered via activation energies, showing decreasing trend with increasing of molecular weight of PEG (except of feedstock containing 1,500 g.mol-1 PEG).

  14. Molecular modeling of nucleic acid structure

    PubMed Central

    Galindo-Murillo, Rodrigo; Bergonzo, Christina

    2013-01-01

    This unit is the first in a series of four units covering the analysis of nucleic acid structure by molecular modeling. This unit provides an overview of computer simulation of nucleic acids. Topics include the static structure model, computational graphics and energy models, generation of an initial model, and characterization of the overall three-dimensional structure. PMID:18428873

  15. A Molecular Model for Chiral Symmetry Breaking

    NASA Astrophysics Data System (ADS)

    Latinwo, Folarin; Stillinger, Frank; Debenedetti, Pablo

    In this work, we present a new class of molecular models for chiral phenomena in condensed matter systems. A key feature of these models is the ability of the four-site (tetramer) ``molecules'' to inter-convert between two distinct chiral forms (enantiomers). Given this feature, we use analytical theory and computer simulations to investigate the emergent chiral properties (including symmetry breaking) over a range of conditions. In particular, we consider the single-molecule level and condensed-phase behavior of our model system. Interestingly, we find that our liquid-phase predictions are in excellent agreement with recent experimental reports on chiral self-sorting in isotropic liquids. From this perspective, our model demonstrates accurate predictive capabilities, as well as a platform for understanding the microscopic origins of a variety of chiral phenomena. In a broader context, we anticipate that this class of models will be relevant to chirality-dominated areas such as the pharmaceutical industry and pre-biotic geochemistry.

  16. Molecular modeling of inelastic electron transport in molecular junctions

    NASA Astrophysics Data System (ADS)

    Jiang, Jun; Kula, Mathias; Luo, Yi

    2008-09-01

    A quantum chemical approach for the modeling of inelastic electron tunneling spectroscopy of molecular junctions based on scattering theory is presented. Within a harmonic approximation, the proposed method allows us to calculate the electron-vibration coupling strength analytically, which makes it applicable to many different systems. The calculated inelastic electron transport spectra are often in very good agreement with their experimental counterparts, allowing the revelation of detailed information about molecular conformations inside the junction, molecule-metal contact structures, and intermolecular interaction that is largely inaccessible experimentally.

  17. Modeling the Hydrogen Bond within Molecular Dynamics

    ERIC Educational Resources Information Center

    Lykos, Peter

    2004-01-01

    The structure of a hydrogen bond is elucidated within the framework of molecular dynamics based on the model of Rahman and Stillinger (R-S) liquid water treatment. Thus, undergraduates are exposed to the powerful but simple use of classical mechanics to solid objects from a molecular viewpoint.

  18. Students' Understanding Is Enhanced through Molecular Modeling

    ERIC Educational Resources Information Center

    Ealy, Julie B.

    2004-01-01

    Integration of molecular modeling into General Chemistry lab encourages students to dually process molecular concepts both verbally and pictorially. When students are tested utilizing questions not previously encountered the dual processing of information can contribute to a transfer to knowledge. General Chemistry students utilized molecular…

  19. Informing Mechanistic Toxicology with Computational Molecular Models

    EPA Science Inventory

    Computational molecular models of chemicals interacting with biomolecular targets provides toxicologists a valuable, affordable, and sustainable source of in silico molecular level information that augments, enriches, and complements in vitro and in vivo effo...

  20. Molecular Modeling of Fluorescent SERCA Biosensors.

    PubMed

    Svensson, Bengt; Autry, Joseph M; Thomas, David D

    2016-01-01

    Molecular modeling and simulation are useful tools in structural biology, allowing the formulation of functional hypotheses and interpretation of spectroscopy experiments. Here, we describe a method to construct in silico models of a fluorescent fusion protein construct, where a cyan fluorescent protein (CFP) is linked to the actuator domain of the Sarco/Endoplasmic Reticulum Ca(2+)-ATPase (SERCA). This CFP-SERCA construct is a biosensor that can report on structural dynamics in the cytosolic headpiece of SERCA. Molecular modeling and FRET experiments allow us to generate new structural and mechanistic models that better describe the conformational landscape and regulation of SERCA. The methods described here can be applied to the creation of models for any fusion protein constructs and also describe the steps needed to simulate FRET results using molecular models.

  1. Investigation of PDE5/PDE6 and PDE5/PDE11 selective potent tadalafil-like PDE5 inhibitors using combination of molecular modeling approaches, molecular fingerprint-based virtual screening protocols and structure-based pharmacophore development.

    PubMed

    Kayık, Gülru; Tüzün, Nurcan Ş; Durdagi, Serdar

    2017-12-01

    The essential biological function of phosphodiesterase (PDE) type enzymes is to regulate the cytoplasmic levels of intracellular second messengers, 3',5'-cyclic guanosine monophosphate (cGMP) and/or 3',5'-cyclic adenosine monophosphate (cAMP). PDE targets have 11 isoenzymes. Of these enzymes, PDE5 has attracted a special attention over the years after its recognition as being the target enzyme in treating erectile dysfunction. Due to the amino acid sequence and the secondary structural similarity of PDE6 and PDE11 with the catalytic domain of PDE5, first-generation PDE5 inhibitors (i.e. sildenafil and vardenafil) are also competitive inhibitors of PDE6 and PDE11. Since the major challenge of designing novel PDE5 inhibitors is to decrease their cross-reactivity with PDE6 and PDE11, in this study, we attempt to identify potent tadalafil-like PDE5 inhibitors that have PDE5/PDE6 and PDE5/PDE11 selectivity. For this aim, the similarity-based virtual screening protocol is applied for the "clean drug-like subset of ZINC database" that contains more than 20 million small compounds. Moreover, molecular dynamics (MD) simulations of selected hits complexed with PDE5 and off-targets were performed in order to get insights for structural and dynamical behaviors of the selected molecules as selective PDE5 inhibitors. Since tadalafil blocks hERG1 K channels in concentration dependent manner, the cardiotoxicity prediction of the hit molecules was also tested. Results of this study can be useful for designing of novel, safe and selective PDE5 inhibitors.

  2. Modeling hybrid perovskites by molecular dynamics

    NASA Astrophysics Data System (ADS)

    Mattoni, Alessandro; Filippetti, Alessio; Caddeo, Claudia

    2017-02-01

    The topical review describes the recent progress in the modeling of hybrid perovskites by molecular dynamics simulations. Hybrid perovskites and in particular methylammonium lead halide (MAPI) have a tremendous technological relevance representing the fastest-advancing solar material to date. They also represent the paradigm of an organic-inorganic crystalline material with some conceptual peculiarities: an inorganic semiconductor for what concerns the electronic and absorption properties with a hybrid and solution processable organic-inorganic body. After briefly explaining the basic concepts of ab initio and classical molecular dynamics, the model potential recently developed for hybrid perovskites is described together with its physical motivation as a simple ionic model able to reproduce the main dynamical properties of the material. Advantages and limits of the two strategies (either ab initio or classical) are discussed in comparison with the time and length scales (from pico to microsecond scale) necessary to comprehensively study the relevant properties of hybrid perovskites from molecular reorientations to electrocaloric effects. The state-of-the-art of the molecular dynamics modeling of hybrid perovskites is reviewed by focusing on a selection of showcase applications of methylammonium lead halide: molecular cations disorder; temperature evolution of vibrations; thermally activated defects diffusion; thermal transport. We finally discuss the perspectives in the modeling of hybrid perovskites by molecular dynamics.

  3. Modeling hybrid perovskites by molecular dynamics.

    PubMed

    Mattoni, Alessandro; Filippetti, Alessio; Caddeo, Claudia

    2017-02-01

    The topical review describes the recent progress in the modeling of hybrid perovskites by molecular dynamics simulations. Hybrid perovskites and in particular methylammonium lead halide (MAPI) have a tremendous technological relevance representing the fastest-advancing solar material to date. They also represent the paradigm of an organic-inorganic crystalline material with some conceptual peculiarities: an inorganic semiconductor for what concerns the electronic and absorption properties with a hybrid and solution processable organic-inorganic body. After briefly explaining the basic concepts of ab initio and classical molecular dynamics, the model potential recently developed for hybrid perovskites is described together with its physical motivation as a simple ionic model able to reproduce the main dynamical properties of the material. Advantages and limits of the two strategies (either ab initio or classical) are discussed in comparison with the time and length scales (from pico to microsecond scale) necessary to comprehensively study the relevant properties of hybrid perovskites from molecular reorientations to electrocaloric effects. The state-of-the-art of the molecular dynamics modeling of hybrid perovskites is reviewed by focusing on a selection of showcase applications of methylammonium lead halide: molecular cations disorder; temperature evolution of vibrations; thermally activated defects diffusion; thermal transport. We finally discuss the perspectives in the modeling of hybrid perovskites by molecular dynamics.

  4. Propagation Modeling and Analysis of Molecular Motors in Molecular Communication.

    PubMed

    Chahibi, Youssef; Akyildiz, Ian F; Balasingham, Ilangko

    2016-10-24

    Molecular motor networks (MMNs) are networks constructed from molecular motors to enable nanomachines to perform coordinated tasks of sensing, computing, and actuation at the nano- and micro- scales. Living cells are naturally enabled with this same mechanism to establish point-to-point communication between different locations inside the cell. Similar to a railway system, the cytoplasm contains an intricate infrastructure of tracks, named microtubules, interconnecting different internal components of the cell. Motor proteins, such as kinesin and dynein, are able to travel along these tracks directionally, carrying with them large molecules that would otherwise be unreliably transported across the cytoplasm using free diffusion. Molecular communication has been previously proposed for the design and study of MMNs. However, the topological aspects of MMNs, including the effects of branches, have been ignored in the existing studies. In this paper, a physical end-to-end model for MMNs is developed, considering the location of the transmitter node, the network topology, and the receiver nodes. The end-to-end gain and group delay are considered as the performance measures, and analytical expressions for them are derived. The analytical model is validated by Monte-Carlo simulations and the performance of MMNs is analyzed numerically. It is shown that, depending on their nature and position, MMN nodes create impedance effects that are critical for the overall performance. This model could be applied to assist the design of artificial MMNs and to study cargo transport in neurofilaments to elucidate brain diseases related to microtubule jamming.

  5. Propagation Modeling and Analysis of Molecular Motors in Molecular Communication.

    PubMed

    Chahibi, Youssef; Akyildiz, Ian F; Balasingham, Ilangko

    2016-12-01

    Molecular motor networks (MMNs) are networks constructed from molecular motors to enable nanomachines to perform coordinated tasks of sensing, computing, and actuation at the nano- and micro- scales. Living cells are naturally enabled with this same mechanism to establish point-to-point communication between different locations inside the cell. Similar to a railway system, the cytoplasm contains an intricate infrastructure of tracks, named microtubules, interconnecting different internal components of the cell. Motor proteins, such as kinesin and dynein, are able to travel along these tracks directionally, carrying with them large molecules that would otherwise be unreliably transported across the cytoplasm using free diffusion. Molecular communication has been previously proposed for the design and study of MMNs. However, the topological aspects of MMNs, including the effects of branches, have been ignored in the existing studies. In this paper, a physical end-to-end model for MMNs is developed, considering the location of the transmitter node, the network topology, and the receiver nodes. The end-to-end gain and group delay are considered as the performance measures, and analytical expressions for them are derived. The analytical model is validated by Monte-Carlo simulations and the performance of MMNs is analyzed numerically. It is shown that, depending on their nature and position, MMN nodes create impedance effects that are critical for the overall performance. This model could be applied to assist the design of artificial MMNs and to study cargo transport in neurofilaments to elucidate brain diseases related to microtubule jamming.

  6. Shock induced phase transition of water: Molecular dynamics investigation

    SciTech Connect

    Neogi, Anupam; Mitra, Nilanjan

    2016-02-15

    Molecular dynamics simulations were carried out using numerous force potentials to investigate the shock induced phenomenon of pure bulk liquid water. Partial phase transition was observed at single shock velocity of 4.0 km/s without requirement of any external nucleators. Change in thermodynamic variables along with radial distribution function plots and spectral analysis revealed for the first time in the literature, within the context of molecular dynamic simulations, the thermodynamic pathway leading to formation of ice VII from liquid water on shock loading. The study also revealed information for the first time in the literature about the statistical time-frame after passage of shock in which ice VII formation can be observed and variations in degree of crystallinity of the sample over the entire simulation time of 100 ns.

  7. Investigation of glassy state molecular motions in thermoset polymers

    NASA Astrophysics Data System (ADS)

    Tu, Jianwei

    This dissertation presents the investigation of the glassy state molecular motions in isomeric thermoset epoxies by means of solid-state deuterium (2H) NMR spectroscopy technique. The network structure of crosslinked epoxies was altered through monomer isomerism; specifically, diglycidyl ether of bisphenol A (DGEBA) was cured with isomeric amine curatives, i.e., the meta-substituted diaminodiphenylsulfone (33DDS) and para-substituted diaminodiphenylsulfone (44DDS). The use of structural isomerism provided a path way for altering macroscopic material properties while maintaining identical chemical composition within the crosslinked networks. The effects of structural isomerism on the glassy state molecular motions were studied using solid-state 2H NMR spectroscopy, which offers unrivaled power to monitor site-specific molecular motions. Three distinctive molecular groups on each isomeric network, i.e., the phenylene rings in the bisphenol A structure (BPA), the phenylene rings in the diaminodiphenylsulfone structure (DDS), and the hydroxypropoyl ether group (HPE) have been selectively deuterated for a comprehensive study of the structure-dynamics- property relationships in thermoset epoxies. Quadrupolar echo experiments and line shape simulations were employed as the main research approach to gain both qualitative and quantitative motional information of the epoxy networks in the glassy state. Quantitative information on the geometry and rate of the molecular motions allows the elucidation of the relationship between molecular motions and macro physical properties and the role of these motions in the mechanical relaxation. Specifically, it is revealed that both the BPA and HPE moieties in the isomeric networks have almost identical behaviors in the deep glassy state, which indicates that the molecular motions in the glassy state are localized, and the correlation length of the motions does not exceed the length of the DGEBA repeat unit. BPA ring motions contribute

  8. First Principles Quantitative Modeling of Molecular Devices

    NASA Astrophysics Data System (ADS)

    Ning, Zhanyu

    In this thesis, we report theoretical investigations of nonlinear and nonequilibrium quantum electronic transport properties of molecular transport junctions from atomistic first principles. The aim is to seek not only qualitative but also quantitative understanding of the corresponding experimental data. At present, the challenges to quantitative theoretical work in molecular electronics include two most important questions: (i) what is the proper atomic model for the experimental devices? (ii) how to accurately determine quantum transport properties without any phenomenological parameters? Our research is centered on these questions. We have systematically calculated atomic structures of the molecular transport junctions by performing total energy structural relaxation using density functional theory (DFT). Our quantum transport calculations were carried out by implementing DFT within the framework of Keldysh non-equilibrium Green's functions (NEGF). The calculated data are directly compared with the corresponding experimental measurements. Our general conclusion is that quantitative comparison with experimental data can be made if the device contacts are correctly determined. We calculated properties of nonequilibrium spin injection from Ni contacts to octane-thiolate films which form a molecular spintronic system. The first principles results allow us to establish a clear physical picture of how spins are injected from the Ni contacts through the Ni-molecule linkage to the molecule, why tunnel magnetoresistance is rapidly reduced by the applied bias in an asymmetric manner, and to what extent ab initio transport theory can make quantitative comparisons to the corresponding experimental data. We found that extremely careful sampling of the two-dimensional Brillouin zone of the Ni surface is crucial for accurate results in such a spintronic system. We investigated the role of contact formation and its resulting structures to quantum transport in several molecular

  9. Investigations of ice nanoparticles and aerosols in molecular beams

    NASA Astrophysics Data System (ADS)

    Farnik, Michal

    2015-03-01

    We have recently set up a versatile experiment which allows for different experiments with molecular clusters and nanoparticles in molecular beams. Here we concentrate on the experiments with ice nanoparticles (large water clusters (H2O)N, N ~ 102-103) doped with atmospherically relevant molecules, e.g., hydrogen halides, CFCs, nitric acid, NxOy, etc. Such species are relevant to ozone depletion and other atmospheric processes. We investigate (1) the UV-photochemistry using velocity map imaging techniques, and (2) the uptake cross section for the molecules on the ice nanoparticles from velocity measurements. In addition, we record (3) mass spectra of the particles implementing different ionization methods: electron ionization (EI) at variable electron energies, photoionization, and special method of electron photodetachment after Na-doping (NaPI). The unique combination of all these different methods performed with the same nanoparticles provides detailed molecular level information about the studied species and their (photo)physics and chemistry. In particular, an investigation of mixed water-nitric acid particles by means of EI and NaPI revealed the prominent role of the HNO3 molecule as the condensation nuclei. The uptake of atmospheric molecules by ice nanoparticles has been studied, and the pickup cross sections for some molecules exceed significantly the geometrical sizes of the ice nanoparticles. It has been argued that the large particles composed of several hundred water molecules which grow in the supersonic expansions tend to have highly irregular shapes -nanosnowflakes. Photodissociation of hydrogen halides on ice nanoparticles has been investigated, and shown to proceed via excitation of acidically dissociated ion pair and subsequent biradical generation and H3O dissociation. The photodissociation of CF2Cl2 molecules in clusters leads to efficient Cl-fragment caging caused by formation of halogen bond. Grant agency of the Czech Republic, Grant No.: 14

  10. Markov state models and molecular alchemy

    NASA Astrophysics Data System (ADS)

    Schütte, Christof; Nielsen, Adam; Weber, Marcus

    2015-01-01

    In recent years, Markov state models (MSMs) have attracted a considerable amount of attention with regard to modelling conformation changes and associated function of biomolecular systems. They have been used successfully, e.g. for peptides including time-resolved spectroscopic experiments, protein function and protein folding , DNA and RNA, and ligand-receptor interaction in drug design and more complicated multivalent scenarios. In this article, a novel reweighting scheme is introduced that allows to construct an MSM for certain molecular system out of an MSM for a similar system. This permits studying how molecular properties on long timescales differ between similar molecular systems without performing full molecular dynamics simulations for each system under consideration. The performance of the reweighting scheme is illustrated for simple test cases, including one where the main wells of the respective energy landscapes are located differently and an alchemical transformation of butane to pentane where the dimension of the state space is changed.

  11. Mesoscale modeling of dislocations in molecular crystals

    NASA Astrophysics Data System (ADS)

    Lei, Lei; Koslowski, Marisol

    2011-02-01

    Understanding the inelastic deformation of molecular crystals is of fundamental importance to the modeling of the processing of drugs in the pharmaceutical industry as well as to the initiation of detonation in high energy density materials. In this work, we present dislocation dynamics simulations of the deformation of two molecular crystals of interest in the pharmaceutical industry, sucrose and paracetamol. The simulations calculate the yield stress of sucrose and paracetamol in good agreement with experimental observation and predict the anisotropy in the mechanical response observed in these materials. Our results show that dislocation dynamics is an effective tool to study plastic deformation in molecular crystals.

  12. Investigating the Postmortem Molecular Biology of Cartilage and its Potential Forensic Applications.

    PubMed

    Bolton, Shawna N; Whitehead, Michael P; Dudhia, Jayesh; Baldwin, Timothy C; Sutton, Raul

    2015-07-01

    This study investigated the postmortem molecular changes that articular cartilage undergoes following burial. Fresh pig trotters were interred in 30-cm-deep graves at two distinct locations exhibiting dissimilar soil environments for up to 42 days. Extracts of the metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joint cartilage from trotters disinterred weekly over 6 weeks were analyzed by Western blot against the monoclonal antibody 2-B-6 to assess aggrecan degradation. In both soil conditions, aggrecan degradation by-products of decreasing molecular size and complexity were observed up to 21 days postmortem. Degradation products were undetected after this time and coincided with MCP/MTP joint exposure to the soil environment. These results show that cartilage proteoglycans undergo an ordered molecular breakdown, the analysis of which may have forensic applications. This model may prove useful for use as a human model and for forensic investigations concerning crimes against animals and the mortality of endangered species.

  13. Exploring Organic Mechanistic Puzzles with Molecular Modeling

    ERIC Educational Resources Information Center

    Horowitz, Gail; Schwartz, Gary

    2004-01-01

    The molecular modeling was used to reinforce more general skills such as deducing and drawing reaction mechanisms, analyzing reaction kinetics and thermodynamics and drawing reaction coordinate energy diagrams. This modeling was done through the design of mechanistic puzzles, involving reactions not familiar to the students.

  14. Learning generative models of molecular dynamics

    PubMed Central

    2012-01-01

    We introduce three algorithms for learning generative models of molecular structures from molecular dynamics simulations. The first algorithm learns a Bayesian-optimal undirected probabilistic model over user-specified covariates (e.g., fluctuations, distances, angles, etc). L1 reg-ularization is used to ensure sparse models and thus reduce the risk of over-fitting the data. The topology of the resulting model reveals important couplings between different parts of the protein, thus aiding in the analysis of molecular motions. The generative nature of the model makes it well-suited to making predictions about the global effects of local structural changes (e.g., the binding of an allosteric regulator). Additionally, the model can be used to sample new conformations. The second algorithm learns a time-varying graphical model where the topology and parameters change smoothly along the trajectory, revealing the conformational sub-states. The last algorithm learns a Markov Chain over undirected graphical models which can be used to study and simulate kinetics. We demonstrate our algorithms on multiple molecular dynamics trajectories. PMID:22369071

  15. A molecular phylogenetic investigation of zoothamnium (ciliophora, peritrichia, sessilida).

    PubMed

    Clamp, John C; Williams, Daniel

    2006-01-01

    The gene coding for 18S small subunit ribosomal RNA (ssu rRNA) was sequenced in seven free-living, marine species of the sessiline peritrich genus Zoothamnium. These were Zoothamnium niveum, Zoothamnium alternans, Zoothamnium pelagicum, and four unidentified species. The ssu rRNA gene also was sequenced in Vorticella convallaria, Vorticella microstoma, and in an unidentified, freshwater species of Vorticella. Phylogenetic trees were constructed using these new sequences to test a previously published phylogenetic association between Zoothamnium arbuscula, currently in the family Zoothamniidae, and peritrichs in the family Vorticellidae. Trees constructed by means of neighbor-joining, maximum parsimony, maximum likelihood, and Bayesian inference methods all had similar topologies. The seven new sequences of Zoothamnium species grouped into three well-supported clades, each of which contained a diversity of morphological types. The three clades formed a poorly supported, larger clade that was deeply divergent from Z. arbuscula, which remained more closely associated with vorticellid peritrichs. It is apparent that Zoothamnium is a richly diverse genus and that a much more intensive investigation, involving both morphological and molecular data and a wider selection of species, will be necessary to resolve its phylogeny. A greater amount of molecular diversity than is predicted by morphological data exists within all major clades of sessiline peritrichs that have been included in molecular phylogenies, indicating that characteristics of stalk and peristomial structure traditionally used to differentiate taxa at the generic level and above may not be uniformly reliable.

  16. Animal Models of Depression: Molecular Perspectives

    PubMed Central

    Krishnan, Vaishnav; Nestler, Eric J.

    2012-01-01

    Much of the current understanding about the pathogenesis of altered mood, impaired concentration and neurovegetative symptoms in major depression has come from animal models. However, because of the unique and complex features of human depression, the generation of valid and insightful depression models has been less straightforward than modeling other disabling diseases like cancer or autoimmune conditions. Today’s popular depression models creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology and automated video-tracking. This chapter reviews depression assays involving acute stress (e.g., forced swim test), models consisting of prolonged physical or social stress (e.g., social defeat), models of secondary depression, genetic models, and experiments designed to elucidate the mechanisms of antidepressant action. These paradigms are critically evaluated in relation to their ease, validity and replicability, the molecular insights that they have provided, and their capacity to offer the next generation of therapeutics for depression. PMID:21225412

  17. Hierarchical Molecular Modelling with Ellipsoids

    SciTech Connect

    Max, N

    2004-03-29

    Protein and DNA structures are represented at varying levels of details using ellipsoidal RGBA textured splats. The splat texture at each level is generated by rendering its children in a hierarchical model, from a distribution of viewing directions, and averaging the result. For rendering, the ellipsoids to be used are chosen adaptively, depending on the distance to the viewpoint. This technique is applied to visualize DNA coiling around nucleosomes in chromosomes.

  18. MODELING MOLECULAR HYPERFINE LINE EMISSION

    SciTech Connect

    Keto, Eric; Rybicki, George

    2010-06-20

    In this paper, we discuss two approximate methods previously suggested for modeling hyperfine spectral line emission for molecules whose collisional transition rates between hyperfine levels are unknown. Hyperfine structure is seen in the rotational spectra of many commonly observed molecules such as HCN, HNC, NH{sub 3}, N{sub 2}H{sup +}, and C{sup 17}O. The intensities of these spectral lines can be modeled by numerical techniques such as {Lambda}-iteration that alternately solve the equations of statistical equilibrium and the equation of radiative transfer. However, these calculations require knowledge of both the radiative and collisional rates for all transitions. For most commonly observed radio frequency spectral lines, only the net collisional rates between rotational levels are known. For such cases, two approximate methods have been suggested. The first method, hyperfine statistical equilibrium, distributes the hyperfine level populations according to their statistical weight, but allows the population of the rotational states to depart from local thermal equilibrium (LTE). The second method, the proportional method, approximates the collision rates between the hyperfine levels as fractions of the net rotational rates apportioned according to the statistical degeneracy of the final hyperfine levels. The second method is able to model non-LTE hyperfine emission. We compare simulations of N{sub 2}H{sup +} hyperfine lines made with approximate and more exact rates and find that satisfactory results are obtained.

  19. Modelling the molecular mechanisms of aging.

    PubMed

    Mc Auley, Mark T; Guimera, Alvaro Martinez; Hodgson, David; Mcdonald, Neil; Mooney, Kathleen M; Morgan, Amy E; Proctor, Carole J

    2017-02-28

    The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field.

  20. Modelling the molecular mechanisms of aging

    PubMed Central

    Mc Auley, Mark T.; Guimera, Alvaro Martinez; Hodgson, David; Mcdonald, Neil; Mooney, Kathleen M.; Morgan, Amy E.

    2017-01-01

    The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field. PMID:28096317

  1. Epigenetic molecular recognition: a biomolecular modeling perspective.

    PubMed

    Vellore, Nadeem A; Baron, Riccardo

    2014-03-01

    The abnormal regulation of epigenetic protein families is associated with the onset and progression of various human diseases. However, epigenetic processes remain relatively obscure at the molecular level, thus preventing the rational design of chemical therapeutics. An array of robust computational and modeling approaches can complement experiments to shed light on the complex mechanisms of epigenetic molecular recognition and can guide medicinal chemists in designing selective and potent drug molecules. Herein we present a review of studies focused on epigenetic molecular recognition from a biomolecular modeling viewpoint. Although the known epigenetic targets are numerous, this review focuses on the more limited protein families on which computational modeling has been successfully applied. Therefore, we review three main topics: 1) histone deacetylases, 2) histone demethylases, and 3) histone tail dynamics. A brief review of the biological background and biomedical relevance is presented for each topic, followed by a detailed discussion of the computational studies and their relevance.

  2. Molecular Modeling of Water Interfaces: From Molecular Spectroscopy to Thermodynamics.

    PubMed

    Nagata, Yuki; Ohto, Tatsuhiko; Backus, Ellen H G; Bonn, Mischa

    2016-04-28

    Understanding aqueous interfaces at the molecular level is not only fundamentally important, but also highly relevant for a variety of disciplines. For instance, electrode-water interfaces are relevant for electrochemistry, as are mineral-water interfaces for geochemistry and air-water interfaces for environmental chemistry; water-lipid interfaces constitute the boundaries of the cell membrane, and are thus relevant for biochemistry. One of the major challenges in these fields is to link macroscopic properties such as interfacial reactivity, solubility, and permeability as well as macroscopic thermodynamic and spectroscopic observables to the structure, structural changes, and dynamics of molecules at these interfaces. Simulations, by themselves, or in conjunction with appropriate experiments, can provide such molecular-level insights into aqueous interfaces. In this contribution, we review the current state-of-the-art of three levels of molecular dynamics (MD) simulation: ab initio, force field, and coarse-grained. We discuss the advantages, the potential, and the limitations of each approach for studying aqueous interfaces, by assessing computations of the sum-frequency generation spectra and surface tension. The comparison of experimental and simulation data provides information on the challenges of future MD simulations, such as improving the force field models and the van der Waals corrections in ab initio MD simulations. Once good agreement between experimental observables and simulation can be established, the simulation can be used to provide insights into the processes at a level of detail that is generally inaccessible to experiments. As an example we discuss the mechanism of the evaporation of water. We finish by presenting an outlook outlining four future challenges for molecular dynamics simulations of aqueous interfacial systems.

  3. Mathematical modeling of molecular diffusion through mucus

    PubMed Central

    Cu, Yen; Saltzman, W. Mark

    2008-01-01

    The rate of molecular transport through the mucus gel can be an important determinant of efficacy for therapeutic agents delivered by oral, intranasal, intravaginal/rectal, and intraocular routes. Transport through mucus can be described by mathematical models based on principles of physical chemistry and known characteristics of the mucus gel, its constituents, and of the drug itself. In this paper, we review mathematical models of molecular diffusion in mucus, as well as the techniques commonly used to measure diffusion of solutes in the mucus gel, mucus gel mimics, and mucosal epithelia. PMID:19135488

  4. Quantum-chemical investigations of small molecular anions

    NASA Astrophysics Data System (ADS)

    Botschwina, P.; Seeger, S.; Mladenović, M.; Schulz, B.; Horn, M.; Schmatz, S.; Flügge, J.; Oswald, R.

    Dedicated to Dr Gerhard Herzberg on the occasion of his 90th birthday Recent large-scale ab initio calculations for small negative molecular ions are reviewed. Accurate equilibrium geometries are established for several species like NH2-, HCC-, NO2-, CH2N- C5- and C6-. Predictions are made for various spectroscopic properties like vibrational frequencies, rotational constants and infrared intensities. The effects of a shallow energy minimum in the T-shaped configuration on the rovibrational term energies of HCC - are investigated. The calculated vibrational structures of the photoelectron spectra of SiH3- and CH2N - are in very good agreement with the experiment. The present calculations support the assignment of an absorption observed at 608 nm in a neon matrix to the

  5. Mobile modeling in the molecular sciences

    EPA Science Inventory

    The art of modeling in the molecular sciences is highly dependent on both the available computational technology, underlying data, and ability to collaborate. With the ever increasing market share of mobile devices, it is assumed by many that tablets will overtake laptops as the...

  6. A quantum mechanical/molecular mechanical approach to the investigation of particle-molecule interactions

    NASA Astrophysics Data System (ADS)

    Sloth, Marianne; Bilde, Merete; Mikkelsen, Kurt V.

    2003-06-01

    A quantum mechanical/molecular mechanical aerosol model is developed to describe the interaction between gas phase molecules and atmospheric particles. The model enables the calculation of interaction energies and time-dependent properties. We use the model to investigate how a succinic acid molecule interacts with an aqueous particle. We show how the interaction energies and linear response properties (excitation energies, transition moments, and polarizabilities) depend on the distance between aerosol particle and molecule and on their relative orientation. The results are compared with those obtained previously using a dielectric continuum model [Sloth et al., J. Phys. Chem. (submitted)].

  7. Molecular simulation and modeling of complex I.

    PubMed

    Hummer, Gerhard; Wikström, Mårten

    2016-07-01

    Molecular modeling and molecular dynamics simulations play an important role in the functional characterization of complex I. With its large size and complicated function, linking quinone reduction to proton pumping across a membrane, complex I poses unique modeling challenges. Nonetheless, simulations have already helped in the identification of possible proton transfer pathways. Simulations have also shed light on the coupling between electron and proton transfer, thus pointing the way in the search for the mechanistic principles underlying the proton pump. In addition to reviewing what has already been achieved in complex I modeling, we aim here to identify pressing issues and to provide guidance for future research to harness the power of modeling in the functional characterization of complex I. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.

  8. Frustration in model glass systems: Numerical investigations

    NASA Astrophysics Data System (ADS)

    Jullien, Rémi; Jund, Philippe; Caprion, Didier; Sadoc, Jean-François

    1999-11-01

    Numerical Voronoï tessellation is used to investigate the mechanisms of frustration in some model glass systems. First, random packings of 8192 hard spheres of increasing volume fraction c are built using an efficient computer algorithm. Their Voronoï statistics evolves with c as if the system would like to reach a pure icosahedral order when extrapolating the volume fraction above the Bernal limit cb≃0.645. Second, super-cooled liquid and glass samples of 1000 atoms are generated at different temperatures T after a quench from the liquid state, using classical micro-canonical molecular dynamics with a simple soft-sphere potential. When decreasing T, the ideal icosahedral order appears again as an extrapolated situation which cannot be realized due to geometrical frustration. Third, a model silica glass of 648 atoms is studied using the potential of van Beest, Kramer and van Santen and a quite similar quenching procedure is performed. As in the soft-sphere case the structural freezing following upon the glass transition is noticeable in all the geometrical characteristics of the Voronoï cells and again a possible interpretation in terms of geometrical frustration is proposed.

  9. Modelling refractive index changes due to molecular interactions

    NASA Astrophysics Data System (ADS)

    Varma, Manoj

    2016-03-01

    There are a large number of sensing techniques which use optical changes to monitor interactions between molecules. In the absence of fluorophores or other labels, the basic signal transduction mechanism relies on refractive index changes arising from the interactions of the molecules involved. A quantitative model incorporating molecular transport, reaction kinetics and optical mixing is presented which reveals important insights concerning the optimal detection of molecular interactions optically. Although conceptually simple, a comprehensive model such as this has not been reported anywhere. Specifically, we investigate the pros and cons of detecting molecular interactions in free solution relative to detecting molecular interactions on surfaces using surface bound receptor molecules such as antibodies. The model reveals that the refractive index change produced in surface based sensors is 2-3 orders of magnitude higher than that from interactions in free solution. On the other hand, the model also reveals that it is indeed possible to distinguish specific molecular interactions from non-specific ones based on free-solution bulk refractometry without any washing step necessary in surface based sensors. However, the refractive index change for free solution interactions predicted by the model is smaller than 10-7 RIU, even for large proteins such as IgG in sufficiently high concentrations. This value is smaller than the typical 10-6 RIU detection limit of most state of the art optical sensing techniques therefore requiring techniques with substantially higher index sensitivity such as Back Scattering Interferometry.

  10. Viscoelasticity in Polymers: Phenomenological to Molecular Mathematical Modelling

    DTIC Science & Technology

    2006-12-14

    of his 80th birthday. Abstract We report on two recent advances in the modelling of viscoelastic polymers: (i) a new constitutive model which combines...the virtual stick-slip continuum “molecular-based” ideas of Johnson and Stacer with the Rouse bead chain ideas; (ii) a two-dimensional version of a ...also loosely re- ferred to as hysteresis) in materials using ideas from elasticity has attracted the attention of a large number of investigators over

  11. The role of molecular modeling in bionanotechnology

    NASA Astrophysics Data System (ADS)

    Lu, Deyu; Aksimentiev, Aleksei; Shih, Amy Y.; Cruz-Chu, Eduardo; Freddolino, Peter L.; Arkhipov, Anton; Schulten, Klaus

    2006-03-01

    Molecular modeling is advocated here as a key methodology for research and development in bionanotechnology. Molecular modeling provides nanoscale images at atomic and even electronic resolution, predicts the nanoscale interaction of unfamiliar combinations of biological and inorganic materials, and evaluates strategies for redesigning biopolymers for nanotechnological uses. The methodology is illustrated in this paper through reviewing three case studies. The first one involves the use of single-walled carbon nanotubes as biomedical sensors where a computationally efficient, yet accurate, description of the influence of biomolecules on nanotube electronic properties through nanotube-biomolecule interactions was developed; this development furnishes the ability to test nanotube electronic properties in realistic biological environments. The second case study involves the use of nanopores manufactured into electronic nanodevices based on silicon compounds for single molecule electrical recording, in particular, for DNA sequencing. Here, modeling combining classical molecular dynamics, material science and device physics, described the interaction of biopolymers, e.g., DNA, with silicon nitrate and silicon oxide pores, furnished accurate dynamic images of pore translocation processes, and predicted signals. The third case study involves the development of nanoscale lipid bilayers for the study of embedded membrane proteins and cholesterol. Molecular modeling tested scaffold proteins, redesigned apolipoproteins found in mammalian plasma that hold the discoidal membranes in the proper shape, and predicted the assembly as well as final structure of the nanodiscs. In entirely new technological areas such as bionanotechnology, qualitative concepts, pictures and suggestions are sorely needed; these three case studies document that molecular modeling can serve a critical role in this respect, even though it may still fall short on quantitative precision.

  12. Gas-phase reactions in extraterrestrial environments: laboratory investigations by crossed molecular beams.

    PubMed

    Balucani, Nadia; Casavecchia, Piergiorgio

    2006-12-01

    We have investigated gas-phase reactions of N((2)D) with the most abundant hydrocarbons in the atmosphere of Titan by the crossed molecular beam technique. In all cases, molecular products containing a novel CN bond are formed, thus suggesting possible routes of formation of gas-phase nitriles in the atmosphere of Titan and primordial Earth. The same approach has been recently extended to the study of radical-radical reactions, such as the reaction of atomic oxygen with the CH(3) and C(3)H(5) radicals. Products other than those already considered in the modeling of planetary atmospheres and interstellar medium have been identified.

  13. Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Jerzy Bernholc

    2011-02-03

    will some day reach a miniaturization limit, forcing designers of Si-based electronics to pursue increased performance by other means. Any other alternative approach would have the unenviable task of matching the ability of Si technology to pack more than a billion interconnected and addressable devices on a chip the size of a thumbnail. Nevertheless, the prospects of developing alternative approaches to fabricate electronic devices have spurred an ever-increasing pace of fundamental research. One of the promising possibilities is molecular electronics (ME), self-assembled molecular-based electronic systems composed of single-molecule devices in ultra dense, ultra fast molecular-sized components. This project focused on developing accurate, reliable theoretical modeling capabilities for describing molecular electronics devices. The participants in the project are given in Table 1. The primary outcomes of this fundamental computational science grant are publications in the open scientific literature. As listed below, 62 papers have been published from this project. In addition, the research has also been the subject of more than 100 invited talks at conferences, including several plenary or keynote lectures. Many of the goals of the original proposal were completed. Specifically, the multi-disciplinary group developed a unique set of capabilities and tools for investigating electron transport in fabricated and self-assembled nanostructures at multiple length and time scales.

  14. Realistic molecular model of kerogen's nanostructure

    NASA Astrophysics Data System (ADS)

    Bousige, Colin; Ghimbeu, Camélia Matei; Vix-Guterl, Cathie; Pomerantz, Andrew E.; Suleimenova, Assiya; Vaughan, Gavin; Garbarino, Gaston; Feygenson, Mikhail; Wildgruber, Christoph; Ulm, Franz-Josef; Pellenq, Roland J.-M.; Coasne, Benoit

    2016-05-01

    Despite kerogen's importance as the organic backbone for hydrocarbon production from source rocks such as gas shale, the interplay between kerogen's chemistry, morphology and mechanics remains unexplored. As the environmental impact of shale gas rises, identifying functional relations between its geochemical, transport, elastic and fracture properties from realistic molecular models of kerogens becomes all the more important. Here, by using a hybrid experimental-simulation method, we propose a panel of realistic molecular models of mature and immature kerogens that provide a detailed picture of kerogen's nanostructure without considering the presence of clays and other minerals in shales. We probe the models' strengths and limitations, and show that they predict essential features amenable to experimental validation, including pore distribution, vibrational density of states and stiffness. We also show that kerogen's maturation, which manifests itself as an increase in the sp2/sp3 hybridization ratio, entails a crossover from plastic-to-brittle rupture mechanisms.

  15. Realistic molecular model of kerogen's nanostructure.

    PubMed

    Bousige, Colin; Ghimbeu, Camélia Matei; Vix-Guterl, Cathie; Pomerantz, Andrew E; Suleimenova, Assiya; Vaughan, Gavin; Garbarino, Gaston; Feygenson, Mikhail; Wildgruber, Christoph; Ulm, Franz-Josef; Pellenq, Roland J-M; Coasne, Benoit

    2016-05-01

    Despite kerogen's importance as the organic backbone for hydrocarbon production from source rocks such as gas shale, the interplay between kerogen's chemistry, morphology and mechanics remains unexplored. As the environmental impact of shale gas rises, identifying functional relations between its geochemical, transport, elastic and fracture properties from realistic molecular models of kerogens becomes all the more important. Here, by using a hybrid experimental-simulation method, we propose a panel of realistic molecular models of mature and immature kerogens that provide a detailed picture of kerogen's nanostructure without considering the presence of clays and other minerals in shales. We probe the models' strengths and limitations, and show that they predict essential features amenable to experimental validation, including pore distribution, vibrational density of states and stiffness. We also show that kerogen's maturation, which manifests itself as an increase in the sp(2)/sp(3) hybridization ratio, entails a crossover from plastic-to-brittle rupture mechanisms.

  16. Molecular model of the neural dopamine transporter

    NASA Astrophysics Data System (ADS)

    Ravna, Aina Westrheim; Sylte, Ingebrigt; Dahl, Svein G.

    2003-05-01

    The dopamine transporter (DAT) regulates the action of dopamine by reuptake of the neurotransmitter into presynaptic neurons, and is the main molecular target of amphetamines and cocaine. DAT and the Na+/H+ antiporter (NhaA) are secondary transporter proteins that carry small molecules across a cell membrane against a concentration gradient, using ion gradients as energy source. A 3-dimensional projection map of the E. coli NhaA has confirmed a topology of 12 membrane spanning domains, and was previously used to construct a 3-dimensional NhaA model with 12 trans-membrane α-helices (TMHs). The NhaA model, and site directed mutagenesis data on DAT, were used to construct a detailed 3-dimensional DAT model using interactive molecular graphics and empiric force field calculations. The model proposes a dopamine transport mechanism involving TMHs 1, 3, 4, 5, 7 and 11. Asp79, Tyr252 and Tyr274 were the primary cocaine binding residues. Binding of cocaine or its analogue, (-)-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT), seemed to lock the transporter in an inactive state, and thus inhibit dopamine transport. The present model may be used to design further experimental studies of the molecular structure and mechanisms of DAT and other secondary transporter proteins.

  17. Application of molecular modeling to biological processing

    NASA Astrophysics Data System (ADS)

    Lowrey, Alfred H.; Famini, George R.; Wick, Charles

    1993-07-01

    Detailed understanding of the molecular basis for biological processes is now available through computational modeling techniques. Advances in computational algorithms and technology allow applications to large biological macromolecules and permits the study of such problems as binding mechanisms, chemical reactivity, structural and conformational effects, and simulations of molecular motions. Recent crystallographic data provides access to detailed structural information that allows analysis and comparison of various computational techniques. Preliminary semiempirical studies on N-acetylneuraminic acid are presented as an example of computational studies on binding mechanisms. N-acetylneuraminic acid is a substituted carbohydrate, which is a recognition site for binding of proteins (i.e., cholera toxin). These calculations provide some insight into electronic effects on bin in a crystal complex and the effect of the molecular charge on hydrogen bonding the crystal complex.

  18. Molecular Dynamics Modeling of Hydrated Calcium-Silicate-Hydrate (CSH) Cement Molecular Structure

    DTIC Science & Technology

    2014-08-30

    properties of key hydrated cement constituent calcium-silicate-hydrate (CSH) at the molecular, nanometer scale level. Due to complexity, still unknown...public release; distribution is unlimited. Molecular Dynamics Modeling of Hydrated Calcium-Silicate- Hydrate (CSH) Cement Molecular Structure The views... Cement Molecular Structure Report Title Multi-scale modeling of complex material systems requires starting from fundamental building blocks to

  19. Spectroscopic investigations, molecular interactions, and molecular docking studies on the potential inhibitor "thiophene-2-carboxylicacid"

    NASA Astrophysics Data System (ADS)

    Karthick, T.; Balachandran, V.; Perumal, S.

    2015-04-01

    Thiophene derivatives have been focused in the past decades due to their remarkable biological and pharmacological activities. In connection with that the conformational stability, spectroscopic characterization, molecular (inter- and intra-) interactions, and molecular docking studies on thiophene-2-carboxylicacid have been performed in this work by experimental FT-IR and theoretical quantum chemical computations. Experimentally recorded FT-IR spectrum in the region 4000-400 cm-1 has been compared with the scaled theoretical spectrum and the spectral peaks have been assigned on the basis of potential energy distribution results obtained from MOLVIB program package. The conformational stability of monomer and dimer conformers has been examined. The presence of inter- and intramolecular interactions in the monomer and dimer conformers have been explained by natural bond orbital analysis. The UV-Vis spectra of the sample in different solvents have been simulated and solvent effects were predicted by polarisable continuum model with TD-DFT/B3LYP/6-31+G(d,p) method. To test the biological activity of the sample, molecular docking (ligand-protein) simulations have been performed using SWISSDOCK web server. The full fitness (FF) score and binding affinity values revealed that thiophene-2-carboxylicacid can act as potential inhibitor against inflammation.

  20. Investigation of the Molecular Response of Belugas to Stressors

    DTIC Science & Technology

    2014-09-30

    To apply molecular methods to describe and quantify changes in the expression of immunological “stress” markers in peripheral blood from captive and...wild belugas. 4. To apply molecular methods to describe and quantify the expression of immunological markers in skin. 5. To correlate the...molecular marker to be used in this study. Being a part of vertebrate innate immune system, Toll-like receptors are located at the direct interface

  1. Molecular Modeling of Nafion Permselective Membranes

    DTIC Science & Technology

    2007-11-02

    Nafion type at mesoscale (>20nm); b) understanding of the mechanisms of sorption and transport of chemical agents in swollen PEM. We developed molecular...models for Nafion and nerve agent simulant DMMP and explored microphase segregation and mechanisms of DMMP sorption and transport in hydrated...was developed for DMMP diffusion in hydrated polymer including volume and surface mechanisms . Simulation results correlate with experimental

  2. Molecular dynamics modelling of solidification in metals

    SciTech Connect

    Boercker, D.B.; Belak, J.; Glosli, J.

    1997-12-31

    Molecular dynamics modeling is used to study the solidification of metals at high pressure and temperature. Constant pressure MD is applied to a simulation cell initially filled with both solid and molten metal. The solid/liquid interface is tracked as a function of time, and the data are used to estimate growth rates of crystallites at high pressure and temperature in Ta and Mg.

  3. Comparative Investigation of Normal Modes and Molecular Dynamics of Hepatitis C NS5B Protein

    NASA Astrophysics Data System (ADS)

    Asafi, M. S.; Yildirim, A.; Tekpinar, M.

    2016-04-01

    Understanding dynamics of proteins has many practical implications in terms of finding a cure for many protein related diseases. Normal mode analysis and molecular dynamics methods are widely used physics-based computational methods for investigating dynamics of proteins. In this work, we studied dynamics of Hepatitis C NS5B protein with molecular dynamics and normal mode analysis. Principal components obtained from a 100 nanoseconds molecular dynamics simulation show good overlaps with normal modes calculated with a coarse-grained elastic network model. Coarse-grained normal mode analysis takes at least an order of magnitude shorter time. Encouraged by this good overlaps and short computation times, we analyzed further low frequency normal modes of Hepatitis C NS5B. Motion directions and average spatial fluctuations have been analyzed in detail. Finally, biological implications of these motions in drug design efforts against Hepatitis C infections have been elaborated.

  4. Fluorescence fluctuation microscopy: a diversified arsenal of methods to investigate molecular dynamics inside cells.

    PubMed

    Weidemann, Thomas; Mücksch, Jonas; Schwille, Petra

    2014-10-01

    Fluorescence microscopy provides insight into the subcellular organization of biological functions. However, images are snap shots averaging over a highly dynamic molecular system. Fluorescence fluctuation microscopy, employing similar detection technology, encompasses a powerful arsenal of analysis tools that investigate the molecular heterogeneity in space and time. Analyzing signal fluctuations from small ensembles (several hundred particles) reveals their concentration, the stoichiometry, the stochastic motion, as well as superimposed signatures of the environment such as spatial confinement and binding events. Thus, fluctuation analysis provides access to dynamic molecular properties that can be used to build physical models of cellular processes. In the last decade these methods experienced a remarkable diversification, which we revisit here with a particular focus on live cell applications.

  5. Mechanical properties of borophene films: a reactive molecular dynamics investigation

    NASA Astrophysics Data System (ADS)

    Quy Le, Minh; Mortazavi, Bohayra; Rabczuk, Timon

    2016-11-01

    The most recent experimental advances could provide ways for the fabrication of several atomic thick and planar forms of boron atoms. For the first time, we explore the mechanical properties of five types of boron films with various vacancy ratios ranging from 0.1-0.15, using molecular dynamics simulations with ReaxFF force field. It is found that the Young’s modulus and tensile strength decrease with increasing the temperature. We found that boron sheets exhibit an anisotropic mechanical response due to the different arrangement of atoms along the armchair and zigzag directions. At room temperature, 2D Young’s modulus and fracture stress of these five sheets appear in the range 63-136 N m-1 and 12-19 N m-1, respectively. In addition, the strains at tensile strength are in the ranges of 9%-14%, 11%-19%, and 10%-16% at 1, 300, and 600 K, respectively. This investigation not only reveals the remarkable stiffness of 2D boron, but establishes relations between the mechanical properties of the boron sheets to the loading direction, temperature and atomic structures.

  6. Investigation of the Composition and Formation Constant of Molecular Complexes

    PubMed Central

    Sahai, R.; Loper, G. L.; Lin, S. H.; Eyring, H.

    1974-01-01

    It has been the purpose of the present paper to investigate and explore the conditions under which the linear relation between Δ/CD0 and Δ in the Hanna-Ashbaugh-Foster-Fyfe equation for the evaluation of equilibrium constants holds, (CD0 is initial concentration of a donor and Δ is the observed chemical shift relative to the chemical shift of the acceptor) to obtain the equation representing the exact linear relation between Δ/CD0 and Δ, when the linear relation between Δ/CD0 and Δ holds, and to discuss how to use the Job method in nuclear magnetic resonance measurements to determine the stoichiometry of molecular complexes. We have found that the conventional belief that CD0 should always be chosen to be much greater than CA0 (initial concentration of acceptor) is not necessarily always true and the exact linear relation between Δ/CD0 and Δ is represented by the equation Δ/CD0 = K1Δ0/(1 + K1CA0) - K1Δ/(1 + K1CA0)2, where K1 is the formation constant of the complex. It is shown that in the Job method of nuclear magnetic resonance measurements one has to plot ΔCA0 against the mole fraction, and the mole fraction at the maximum should give us the composition of the complex. Theoretical results have been verified experimentally on the weak interaction between naphthalene and methyl iodide. PMID:16592155

  7. Investigation of synthetic molecular recognition for biosensing applications

    NASA Astrophysics Data System (ADS)

    Stratis-Cullum, Dimitra N.; McMasters, Sun; Sooter, Letha J.; Pellegrino, Paul M.

    2007-04-01

    A fundamental understanding of the factors which influence binding performance is critical to any technology or methodology relying on molecular recognition of a specific target species. For the Army, there is a growing need for a basic understanding of these interactions with traditional recognition elements (e.g., antibodies) in non-traditional environmental conditions, such as with new and emerging threats. There is a similar need for building a base of knowledge on non-traditional affinity ligands that are biomimetic or biosynthetic in nature. In this paper, specific research at the Army Research Laboratory towards the development, evaluation and use of synthetic affinity ligands for sensing applications is discussed. This includes the results of our investigations of aptamer-based affinity ligands targeting Campylobacter jejuni. Using capillary electrophoretic techniques, the relative binding affinities of the aptamer ligands towards the target pathogen as well as the degree of cross-reactivity with other food borne-pathogens (i.e., Escherichia coli O157:H7 and Salmonella typhimurium) were evaluated. Current progress towards the development of synthetic affinity ligands for sensing applications will also be discussed.

  8. Teaching Molecular Geometry with the VSEPR Model

    NASA Astrophysics Data System (ADS)

    Gillespie, Ronald J.

    2004-03-01

    Molecular geometry can be discussed in terms of the VSEPR model at several levels of sophistication—from the empirical model to a more complete model based on the Pauli principle. It is recommended that for most first-year courses VSEPR is presented at the purely empirical level or in the form of the domain version. A more sophisticated version is discussed here, not only because it should be taught in more advanced courses, but because it is important that it is understood by instructors and textbook writers so that incorrect explanations of the VSEPR model are not given. The difficulties associated with the usual treatment of the VB and MO theories in connection with molecular geometry in beginning courses are discussed. It is recommended that the VB and MO theories should be presented only after the VSEPR model either in the general chemistry course or in a following course, particularly in the case of the MO theory, which is not really necessary for the first-year course. The Pauli principle and its importance as the fundamental basis of the VSEPR model should be presented in a higher-level course, such as a quantum mechanics or physical chemistry course, or an inorganic course, in which VSEPR has many applications, for example, in the discussion of noble gas and other high coordination number molecules.

  9. Atomistic molecular dynamics simulations of model C36 fullerite

    NASA Astrophysics Data System (ADS)

    Abramo, Maria C.; Caccamo, C.

    2008-02-01

    We report atomistic molecular dynamics investigations of a model C36 fullerite in which the fullerene molecules are modeled as rigid cages over which the carbon atoms occupy fixed interaction sites, distributed in space according to the experimentally known atomic positions in the molecule. Carbon sites belonging to different molecules are assumed to interact via a 12-6 Lennard-Jones-type potential; the parameters of the latter are employed in the framework of a molecular dynamics fitting procedure, through which the ambient condition physical quantities characterizing the hcp structure of solid C36 are eventually reproduced. We discuss applications of the adopted modelization to the C36 phases in a temperature range spanning from 300to1500K, and compare the obtained results to the available data for C36 and other fullerenes, and to the predictions of the well known Girifalco central potential modelization of interactions in fullerenes, as applied to the C36 case.

  10. High-School Chemistry Students' Performance and Gender Differences in a Computerized Molecular Modeling Learning Environment.

    ERIC Educational Resources Information Center

    Barnea, Nitza; Dori, Yehudit J.

    1999-01-01

    Investigates the effects of using molecular modeling on students' spatial ability, understanding of new concepts related to geometric and symbolic representations, and perception of the model concept. (Author/CCM)

  11. Molecular Epidemiology Investigation of Obesity and Lethal Prostate Cancer

    DTIC Science & Technology

    2015-09-01

    in the field of molecular epidemiology. During the award period the PI performed research incorporating tissue -level biomarker data into...Using whole transcriptome gene expression profiling data, she identified a chromatin gene signature that is enriched in the tumor tissue of overweight...prostate cancer, obesity, tissue biomarkers, gene expression, growth factor signaling, inflammation, angiogenesis, molecular epidemiology 16

  12. Investigations on Binding Pattern of Kinase Inhibitors with PPARγ: Molecular Docking, Molecular Dynamic Simulations, and Free Energy Calculation Studies

    PubMed Central

    Mazumder, Mohit; Das, Umashankar; Gourinath, Samudrala

    2017-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a potential target for the treatment of several disorders. In view of several FDA approved kinase inhibitors, in the current study, we have investigated the interaction of selected kinase inhibitors with PPARγ using computational modeling, docking, and molecular dynamics simulations (MDS). The docked conformations and MDS studies suggest that the selected KIs interact with PPARγ in the ligand binding domain (LBD) with high positive predictive values. Hence, we have for the first time shown the plausible binding of KIs in the PPARγ ligand binding site. The results obtained from these in silico investigations warrant further evaluation of kinase inhibitors as PPARγ ligands in vitro and in vivo. PMID:28321247

  13. Molecular model with quantum mechanical bonding information.

    PubMed

    Bohórquez, Hugo J; Boyd, Russell J; Matta, Chérif F

    2011-11-17

    The molecular structure can be defined quantum mechanically thanks to the theory of atoms in molecules. Here, we report a new molecular model that reflects quantum mechanical properties of the chemical bonds. This graphical representation of molecules is based on the topology of the electron density at the critical points. The eigenvalues of the Hessian are used for depicting the critical points three-dimensionally. The bond path linking two atoms has a thickness that is proportional to the electron density at the bond critical point. The nuclei are represented according to the experimentally determined atomic radii. The resulting molecular structures are similar to the traditional ball and stick ones, with the difference that in this model each object included in the plot provides topological information about the atoms and bonding interactions. As a result, the character and intensity of any given interatomic interaction can be identified by visual inspection, including the noncovalent ones. Because similar bonding interactions have similar plots, this tool permits the visualization of chemical bond transferability, revealing the presence of functional groups in large molecules.

  14. A Series of Molecular Dynamics and Homology Modeling Computer Labs for an Undergraduate Molecular Modeling Course

    ERIC Educational Resources Information Center

    Elmore, Donald E.; Guayasamin, Ryann C.; Kieffer, Madeleine E.

    2010-01-01

    As computational modeling plays an increasingly central role in biochemical research, it is important to provide students with exposure to common modeling methods in their undergraduate curriculum. This article describes a series of computer labs designed to introduce undergraduate students to energy minimization, molecular dynamics simulations,…

  15. Modeling molecular mechanisms in the axon

    NASA Astrophysics Data System (ADS)

    de Rooij, R.; Miller, K. E.; Kuhl, E.

    2016-12-01

    Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena—both in isolation and in interaction—to explore emergent cellular-level features under physiological and pathological conditions.

  16. Modeling molecular mechanisms in the axon

    NASA Astrophysics Data System (ADS)

    de Rooij, R.; Miller, K. E.; Kuhl, E.

    2017-03-01

    Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena—both in isolation and in interaction—to explore emergent cellular-level features under physiological and pathological conditions.

  17. A realistic molecular model of cement hydrates

    PubMed Central

    Pellenq, Roland J.-M.; Kushima, Akihiro; Shahsavari, Rouzbeh; Van Vliet, Krystyn J.; Buehler, Markus J.; Yip, Sidney; Ulm, Franz-Josef

    2009-01-01

    Despite decades of studies of calcium-silicate-hydrate (C-S-H), the structurally complex binder phase of concrete, the interplay between chemical composition and density remains essentially unexplored. Together these characteristics of C-S-H define and modulate the physical and mechanical properties of this “liquid stone” gel phase. With the recent determination of the calcium/silicon (C/S = 1.7) ratio and the density of the C-S-H particle (2.6 g/cm3) by neutron scattering measurements, there is new urgency to the challenge of explaining these essential properties. Here we propose a molecular model of C-S-H based on a bottom-up atomistic simulation approach that considers only the chemical specificity of the system as the overriding constraint. By allowing for short silica chains distributed as monomers, dimers, and pentamers, this C-S-H archetype of a molecular description of interacting CaO, SiO2, and H2O units provides not only realistic values of the C/S ratio and the density computed by grand canonical Monte Carlo simulation of water adsorption at 300 K. The model, with a chemical composition of (CaO)1.65(SiO2)(H2O)1.75, also predicts other essential structural features and fundamental physical properties amenable to experimental validation, which suggest that the C-S-H gel structure includes both glass-like short-range order and crystalline features of the mineral tobermorite. Additionally, we probe the mechanical stiffness, strength, and hydrolytic shear response of our molecular model, as compared to experimentally measured properties of C-S-H. The latter results illustrate the prospect of treating cement on equal footing with metals and ceramics in the current application of mechanism-based models and multiscale simulations to study inelastic deformation and cracking. PMID:19805265

  18. A realistic molecular model of cement hydrates.

    PubMed

    Pellenq, Roland J-M; Kushima, Akihiro; Shahsavari, Rouzbeh; Van Vliet, Krystyn J; Buehler, Markus J; Yip, Sidney; Ulm, Franz-Josef

    2009-09-22

    Despite decades of studies of calcium-silicate-hydrate (C-S-H), the structurally complex binder phase of concrete, the interplay between chemical composition and density remains essentially unexplored. Together these characteristics of C-S-H define and modulate the physical and mechanical properties of this "liquid stone" gel phase. With the recent determination of the calcium/silicon (C/S = 1.7) ratio and the density of the C-S-H particle (2.6 g/cm(3)) by neutron scattering measurements, there is new urgency to the challenge of explaining these essential properties. Here we propose a molecular model of C-S-H based on a bottom-up atomistic simulation approach that considers only the chemical specificity of the system as the overriding constraint. By allowing for short silica chains distributed as monomers, dimers, and pentamers, this C-S-H archetype of a molecular description of interacting CaO, SiO2, and H2O units provides not only realistic values of the C/S ratio and the density computed by grand canonical Monte Carlo simulation of water adsorption at 300 K. The model, with a chemical composition of (CaO)(1.65)(SiO2)(H2O)(1.75), also predicts other essential structural features and fundamental physical properties amenable to experimental validation, which suggest that the C-S-H gel structure includes both glass-like short-range order and crystalline features of the mineral tobermorite. Additionally, we probe the mechanical stiffness, strength, and hydrolytic shear response of our molecular model, as compared to experimentally measured properties of C-S-H. The latter results illustrate the prospect of treating cement on equal footing with metals and ceramics in the current application of mechanism-based models and multiscale simulations to study inelastic deformation and cracking.

  19. Molecular dynamics investigation of mechanisms of femtosecond laser ablation

    NASA Astrophysics Data System (ADS)

    Cheng, Changrui

    Laser micro-machining has been widely applied for material processing in many industries. A phenomenon called "laser ablation" is usually involved in the laser micro-machining process. Laser ablation is the process of material removal after the irradiation of a laser beam onto the material. It is commonly characterized by small temporal and spatial scales, extremely high material temperature and pressure, and strong non-equilibrium thermodynamic state. In this work, molecular dynamics (MD) simulation is conducted to study the femtosecond laser ablation of metals (nickel and copper) and dielectrics (fused silica, or glass). The laser heating and the ablation processes are numerically modeled, and the computation is accelerated by parallel processing technique. Both the pair-wise Morse potential and the many-body EAM (Embedded-Atom Method) potential are employed for metals. In the simulation of fused silica, the BKS (van Beest, Kramer and van Santen) potential is used, and the generation of free electrons, the energy transport from laser beam to free electrons and energy coupling between electrons and the lattice are considered. The main goal of this work is to illustrate the detailed processes of femtosecond laser ablation and to study its mechanisms. From the MD results, it is found that the mechanism of femtosecond laser ablation is strongly dependent on the laser fluences. For metals, low fluence laser ablation is mainly through phase explosion (homogeneous gas bubble nucleation), while spinodal decomposition is responsible for high fluence ablation. Ablation mechanism is determined by whether or not the material (liquid) temperature exceeds the critical temperature. For fused silica, the generation and existence of free electrons are found to affect ablation significantly, especially at low fluence, where Coulomb explosion is found to play an important role in material separation.

  20. Molecular sonography with targeted microbubbles: current investigations and potential applications.

    PubMed

    Hwang, Misun; Lyshchik, Andrej; Fleischer, Arthur C

    2010-06-01

    Sonography using targeted microbubbles affords a variety of diagnostic and potentially therapeutic clinical applications. It provides a whole new world of functional information at the cellular and molecular level. This information can then be used to diagnose and possibly prevent diseases at early stages as well as devise therapeutic strategies at the molecular level. It is also useful in monitoring tumor response to therapy and devising treatment timing and plans based on the molecular state of an individual's health. Moreover, targeted microbubble-enhanced sonography has several advantages over other imaging modalities, including widespread availability, low cost, fast acquisition times, and lack of radiation risk. These traits are likely to advance it as one of the imaging methods of choice in future clinical trials examining the impact of molecular imaging on treatment outcome. This review describes the fundamental concepts of targeted microbubble-enhanced sonography as well as its potential clinical applications.

  1. Molecular recognition effects in atomistic models of imprinted polymers.

    PubMed

    Dourado, Eduardo M A; Herdes, Carmelo; van Tassel, Paul R; Sarkisov, Lev

    2011-01-01

    In this article we present a model for molecularly imprinted polymers, which considers both complexation processes in the pre-polymerization mixture and adsorption in the imprinted structures within a single consistent framework. As a case study we investigate MAA/EGDMA polymers imprinted with pyrazine and pyrimidine. A polymer imprinted with pyrazine shows substantial selectivity towards pyrazine over pyrimidine, thus exhibiting molecular recognition, whereas the pyrimidine imprinted structure shows no preferential adsorption of the template. Binding sites responsible for the molecular recognition of pyrazine involve one MAA molecule and one EGDMA molecule, forming associations with the two functional groups of the pyrazine molecule. Presence of these specific sites in the pyrazine imprinted system and lack of the analogous sites in the pyrimidine imprinted system is directly linked to the complexation processes in the pre-polymerization solution. These processes are quite different for pyrazine and pyrimidine as a result of both enthalpic and entropic effects.

  2. Molecular Models of Liquid Crystal Elastomers

    NASA Astrophysics Data System (ADS)

    Rajshekhar

    Liquid crystal elastomers combine the elastic properties of conventional rubbers with the optical properties of liquid crystals. This dual nature gives rise to unusual physical properties, including the stress induced transition from a polydomain state, consisting of multiple nematic regions with independent orientations, to a monodomain state consisting of a single nematic region with a uniform director. We propose several molecular-scale coarse-grained models of liquid crystal elastomers with varying degrees of resolution. The models employ the Gay-Berne soft potential, and exhibit the chain connectivity of a diamond network. Simulation results show that these models are able to capture the polydomain state exhibited by liquid crystal elastomers in the absence of any external stress. When subjected to uniaxial stress, our models exhibit a polydomain to monodomain transition. We explain that the polydomain state occurs through the aggregation of liquid crystal molecules assisted by crosslinking sites, and conclude that the transition mechanism to the monodomain state is based on the reorientation of nematic domains along the direction of applied stress. Our modeling efforts are primarily focused on three models. The first two models consider the effects of rigid and flexible crosslinkers in liquid crystal elastomers with a diamond topology for chain connectivity. The third model deviates from the diamond network topology and adopts a random network topology.

  3. Effect of molecular models on viscosity and thermal conductivity calculations

    NASA Astrophysics Data System (ADS)

    Weaver, Andrew B.; Alexeenko, Alina A.

    2014-12-01

    The effect of molecular models on viscosity and thermal conductivity calculations is investigated. The Direct Simulation Monte Carlo (DSMC) method for rarefied gas flows is used to simulate Couette and Fourier flows as a means of obtaining the transport coefficients. Experimental measurements for argon (Ar) provide a baseline for comparison over a wide temperature range of 100-1,500 K. The variable hard sphere (VHS), variable soft sphere (VSS), and Lennard-Jones (L-J) molecular models have been implemented into a parallel version of Bird's one-dimensional DSMC code, DSMC1, and the model parameters have been recalibrated to the current experimental data set. While the VHS and VSS models only consider the short-range, repulsive forces, the L-J model also includes constributions from the long-range, dispersion forces. Theoretical results for viscosity and thermal conductivity indicate the L-J model is more accurate than the VSS model; with maximum errors of 1.4% and 3.0% in the range 300-1,500 K for L-J and VSS models, respectively. The range of validity of the VSS model is extended to 1,650 K through appropriate choices for the model parameters.

  4. Molecular modeling of auxin transport inhibitors

    SciTech Connect

    Gardner, G.; Black-Schaefer, C.; Bures, M.G. )

    1990-05-01

    Molecular modeling techniques have been used to study the chemical and steric properties of auxin transport inhibitors. These bind to a specific site on the plant plasma membrane characterized by its affinity for N-1-naphthylphthalamic acid (NPA). A three-dimensional model was derived from critical features of ligands for the NPA receptor, and a suggested binding conformation is proposed. This model, along with three-dimensional structural searching techniques, was then used to search the Abbott corporate database of chemical structures. Of the 467 compounds that satisfied the search criteria, 77 representative molecules were evaluated for their ability to compete for ({sup 3}H)NPA binding to corn microsomal membranes. Nineteen showed activity that ranged from 16 to 85% of the maximum NPA binding. Four of the most active of these, from chemical classes not included in the original compound set, also inhibited polar auxin transport through corn coleoptile sections.

  5. Investigations of physical model of biological tissue

    NASA Astrophysics Data System (ADS)

    Linkov, Kirill G.; Kisselev, Gennady L.; Loschenov, Victor B.

    1996-12-01

    Physical model of a biological tissue for comparison with earlier created mathematical model of a biological tissue and researches of distribution photosensitizer in a depth was created and investigated. Mathematical model is based on granulated representation of optical medium. The model of a biological tissue was created on the basis of enough thin layers of a special material. For fluorescence excitation laser sources with a various wavelength were used. For investigation of scattering and fluorescent signal laser- fiber spectrum-analyzer LESA-5 was applied. Water solution of aluminum phthalocyanine and oil solution of zinc phthalocyanine were used for receiving of fluorescent signal. Created samples have certain absorbing and fluorescent properties. Scattering properties of samples are close to scattering properties of real human skin. By virtue of layered structure the model permits to simulate as a biological tissue without photosensitizer accumulation in it, as tissue with photosensitizer accumulation with certain distribution in a depth. Dependence of fields distribution on a surface was investigated at change of parameters of a model. Essential changes of distribution on a surface depending on the characteristics of model was revealed. The space and angular characteristics was investigated also. The investigations with physical model correspond to predicted results of theoretical model.

  6. On the coalescence-dispersion modeling of turbulent molecular mixing

    NASA Technical Reports Server (NTRS)

    Givi, Peyman; Kosaly, George

    1987-01-01

    The general coalescence-dispersion (C/D) closure provides phenomenological modeling of turbulent molecular mixing. The models of Curl and Dopazo and O'Brien appear as two limiting C/D models that bracket the range of results one can obtain by various models. This finding is used to investigate the sensitivtiy of the results to the choice of the model. Inert scalar mixing is found to be less model-sensitive than mixing accompanied by chemical reaction. Infinitely fast chemistry approximation is used to relate the C/D approach to Toor's earlier results. Pure mixing and infinite rate chemistry calculations are compared to study further a recent result of Hsieh and O'Brien who found that higher concentration moments are not sensitive to chemistry.

  7. Molecular model and ReaxFF molecular dynamics simulation of coal vitrinite pyrolysis.

    PubMed

    Li, Wu; Zhu, Yan-ming; Wang, Geoff; Wang, Yang; Liu, Yu

    2015-08-01

    Vitrinite in coal, the mainly generating methane maceral, plays an important role in hydrocarbon generation of coal. This study aims at obtaining products formation mechanism of vitrinite pyrolysis, and hence determining the chemical bond, molecular liquefaction activity, and reactions mechanism of methane and C2-4 during pyrolysis. The ReaxFF molecular dynamics (MD) simulation was carried out at temperature of 1500 K in order to investigate the mechanism of vitrinite pyrolysis. Initially, a minimum energy conformational structure model was constrained by a combination of elemental and carbon-13 nuclear magnetic resonance ((13)C NMR) literature data. The model analysis shows the chemical and physical parameters of vitrinite pyrolysis are broadly consistent with the experimental data. Based on the molecular model, ReaxFF MD simulations further provide information of unimolecule such as bond length, and chemical shift, and hence the total population and energy of main products. Molecules bond and pyrolysis fragments, based on active bond analyzed, revealed pyrolysis products of single vitrinite molecule with aliphatic C-C bond, especially ring and chain aliphatic as liquefaction activity. The molecular cell whose density is 0.9 g/cm(3) with lowest energy accords with the experimental density 1.33 g/cm(3). The content of main products after pyrolysis, classifying as CH4, H2O, and H2, was changed along with the increasing temperature. The gas molecule, fragments and generation pathways of CO2, H2, CH4, and C2H6 were also elucidated. These results show agreement with experimental observations, implying that MD simulation can provide reasonable explanation for the reaction processes involved in coal vitrinite pyrolysis. Thus the mechanism of coal hydrocarbon generation was revealed at the molecular level.

  8. [Molecular genetic investigation of sugar beet (Beta vulgaris L.)].

    PubMed

    Butorina, A K; Kornienko, A V

    2011-10-01

    Molecular genetic studies of sugar beet (Beta vulgaris L.) are reviewed as a basis for the development of genomics of this species. The methods used to study structural and functional genomics are considered. The results and their application to increase the efficiency of sugar beet breeding are discussed.

  9. Molecular modelling of protein-protein/protein-solvent interactions

    NASA Astrophysics Data System (ADS)

    Luchko, Tyler

    The inner workings of individual cells are based on intricate networks of protein-protein interactions. However, each of these individual protein interactions requires a complex physical interaction between proteins and their aqueous environment at the atomic scale. In this thesis, molecular dynamics simulations are used in three theoretical studies to gain insight at the atomic scale about protein hydration, protein structure and tubulin-tubulin (protein-protein) interactions, as found in microtubules. Also presented, in a fourth project, is a molecular model of solvation coupled with the Amber molecular modelling package, to facilitate further studies without the need of explicitly modelled water. Basic properties of a minimally solvated protein were calculated through an extended study of myoglobin hydration with explicit solvent, directly investigating water and protein polarization. Results indicate a close correlation between polarization of both water and protein and the onset of protein function. The methodology of explicit solvent molecular dynamics was further used to study tubulin and microtubules. Extensive conformational sampling of the carboxy-terminal tails of 8-tubulin was performed via replica exchange molecular dynamics, allowing the characterisation of the flexibility, secondary structure and binding domains of the C-terminal tails through statistical analysis methods. Mechanical properties of tubulin and microtubules were calculated with adaptive biasing force molecular dynamics. The function of the M-loop in microtubule stability was demonstrated in these simulations. The flexibility of this loop allowed constant contacts between the protofilaments to be maintained during simulations while the smooth deformation provided a spring-like restoring force. Additionally, calculating the free energy profile between the straight and bent tubulin configurations was used to test the proposed conformational change in tubulin, thought to cause microtubule

  10. Molecular Investigations into the Mechanics of a Muscle Anchoring Complex

    PubMed Central

    Bodmer, Nicholas K.; Theisen, Kelly E.; Dima, Ruxandra I.

    2015-01-01

    The titin-telethonin complex, essential for anchoring filaments in the Z-disk of the sarcomere, is composed of immunoglobulin domains. Surprisingly, atomic force microscopy experiments showed that it resists forces much higher than the typical immunoglobulin domain and that the force distribution is unusually broad. To investigate the origin of this behavior, we developed a multiscale simulation approach, combining minimalist and atomistic models (SOP-AT). By following the mechanical response of the complex on experimental timescales, we found that the mechanical stability of titin-telethonin is modulated primarily by the strength of contacts between telethonin and the two titin chains, and secondarily by the timescales of conformational excursions inside telethonin and the pulled titin domains. Importantly, the conformational transitions executed by telethonin in simulations support its proposed role in mechanosensing. Our SOP-AT computational approach thus provides a powerful tool for the exploration of the link between conformational diversity and the broadness of the mechanical response, which can be applied to other multidomain complexes. PMID:25954889

  11. Yield and Failure Behavior Investigated for Cross-Linked Phenolic Resins Using Molecular Dynamics

    NASA Technical Reports Server (NTRS)

    Monk, Joshua D.; Lawson, John W.

    2016-01-01

    Molecular dynamics simulations were conducted to fundamentally evaluate the yield and failure behavior of cross-linked phenolic resins at temperatures below the glass transition. Yield stress was investigated at various temperatures, strain rates, and degrees of cross-linking. The onset of non-linear behavior in the cross-linked phenolic structures was caused by localized irreversible molecular rearrangements through the rotation of methylene linkers followed by the formation or annihilation of neighboring hydrogen bonds. The yield stress results, with respect to temperature and strain rate, could be fit by existing models used to describe yield behavior of amorphous glasses. The degree of cross-linking only indirectly influences the maximum yield stress through its influence on glass transition temperature (Tg), however there is a strong relationship between the degree of cross-linking and the failure mechanism. Low cross-linked samples were able to separate through void formation, whereas the highly cross-linked structures exhibited bond scission.

  12. Synchrotron based mass spectrometry to investigate the molecular properties of mineral-organic associations

    SciTech Connect

    Liu, Suet Yi; Kleber, Markus; Takahashi, Lynelle K.; Nico, Peter; Keiluweit, Marco; Ahmed, Musahid

    2013-04-01

    Soil organic matter (OM) is important because its decay drives life processes in the biosphere. Analysis of organic compounds in geological systems is difficult because of their intimate association with mineral surfaces. To date there is no procedure capable of quantitatively separating organic from mineral phases without creating artifacts or mass loss. Therefore, analytical techniques that can (a) generate information about both organic and mineral phases simultaneously and (b) allow the examination of predetermined high-interest regions of the sample as opposed to conventional bulk analytical techniques are valuable. Laser Desorption Synchrotron Postionization (synchrotron-LDPI) mass spectrometry is introduced as a novel analytical tool to characterize the molecular properties of organic compounds in mineral-organic samples from terrestrial systems, and it is demonstrated that when combined with Secondary Ion Mass Spectrometry (SIMS), can provide complementary information on mineral composition. Mass spectrometry along a decomposition gradient in density fractions, verifies the consistency of our results with bulk analytical techniques. We further demonstrate that by changing laser and photoionization energies, variations in molecular stability of organic compounds associated with mineral surfaces can be determined. The combination of synchrotron-LDPI and SIMS shows that the energetic conditions involved in desorption and ionization of organic matter may be a greater determinant of mass spectral signatures than the inherent molecular structure of the organic compounds investigated. The latter has implications for molecular models of natural organic matter that are based on mass spectrometric information.

  13. Investigating Molecular Kinetics by Variationally Optimized Diffusion Maps.

    PubMed

    Boninsegna, Lorenzo; Gobbo, Gianpaolo; Noé, Frank; Clementi, Cecilia

    2015-12-08

    Identification of the collective coordinates that describe rare events in complex molecular transitions such as protein folding has been a key challenge in the theoretical molecular sciences. In the Diffusion Map approach, one assumes that the molecular configurations sampled have been generated by a diffusion process, and one uses the eigenfunctions of the corresponding diffusion operator as reaction coordinates. While diffusion coordinates (DCs) appear to provide a good approximation to the true dynamical reaction coordinates, they are not parametrized using dynamical information. Thus, their approximation quality could not, as yet, be validated, nor could the diffusion map eigenvalues be used to compute relaxation rate constants of the system. Here we combine the Diffusion Map approach with the recently proposed Variational Approach for Conformation Dynamics (VAC). Diffusion Map coordinates are used as a basis set, and their optimal linear combination is sought using the VAC, which employs time-correlation information on the molecular dynamics (MD) trajectories. We have applied this approach to ultra-long MD simulations of the Fip35 WW domain and found that the first DCs are indeed a good approximation to the true reaction coordinates of the system, but they could be further improved using the VAC. Using the Diffusion Map basis, excellent approximations to the relaxation rates of the system are obtained. Finally, we evaluate the quality of different metric spaces and find that pairwise minimal root-mean-square deviation performs poorly, while operating in the recently introduced kinetic maps based on the time-lagged independent component analysis gives the best performance.

  14. Polymorphism and disorder in caffeine: Dielectric investigation of molecular mobilities

    NASA Astrophysics Data System (ADS)

    Descamps, M.; Decroix, A. A.

    2014-12-01

    Using dielectric relaxation data we have characterized the molecular mobilities of caffeine both in phase I (stable and metastable) and in phase II. In phase I effects of sublimation and phase transformation kinetics were carefully considered. In plane rotational motions were followed on a wide temperature range. A noticeable antiferroelectric short range order developing at the approach of the glass-like transition is characterized. Condition for occurrence of a critical-like behaviour is discussed. At high temperature the emergence of an additional ultra slow relaxation process is highlighted. Possible molecular mechanisms are proposed for both processes. In phase II the existence of a less intense relaxation process is confirmed. Close similarity with the main process developing in phase I hints at a common origin of the dipolar motions. Careful consideration of recent structure determinations leads to suggest that this process is associated to similar molecular in plane rotations but developing at the surface of crystalline samples. Lower cooperativity at the surface is reflected in the smaller activation entropy of the relaxation.

  15. Molecular dynamics investigation of the effect of copper nanoparticle on the solid contact between friction surfaces

    NASA Astrophysics Data System (ADS)

    Hu, Chengzhi; Bai, Minli; Lv, Jizu; Liu, Hao; Li, Xiaojie

    2014-12-01

    This study investigated the effect of copper (Cu) nanoparticles on the solid contact between friction surfaces by applying a molecular dynamics method to reveal the mechanisms responsible for the favorable friction properties of nanoparticles. Two models were built, which were named model A (without Cu) and model B (with Cu), respectively. The differences in the mechanical properties between these two models were compared. The simulation results demonstrated that the improvement in friction properties by Cu nanoparticles was more obvious at low velocity than at high velocity. At low velocity, a Cu nano-film was formed on the friction surface, which accommodated the velocity gradient and plastic deformation. Due to the good lubrication effect of the nano-film, the plastic deformation, defect structures and friction force of model B were improved compared with model A. Under high velocity conditions, a transfer layer appeared adjacent to the interface in both models. Because of this, the friction forces of the two models decreased with increased velocity. The fluid mechanics theory was used to explain why the friction force in model B was lower than that in model A at high velocity. The effect of the load on friction properties was also analyzed and the results showed that the mechanisms of anti-wear and friction reduction by Cu nanoparticles under a low load were the same as those under a high load.

  16. Some Reflections on the Use and Abuse of Molecular Models

    ERIC Educational Resources Information Center

    Petersen, Quentin R.

    1970-01-01

    Describes the historical applications of molecular models and the controversies which they produced. The author discusses types of molecular models from the van't Hoff and Kekule models to the more recently developed ones. He presents a new model which was constructed to overcome the disadvantages of (1) falling apart, (2) inaccurate angles, (3)…

  17. Ab Initio Modeling of Molecular Radiation

    NASA Technical Reports Server (NTRS)

    Jaffe, Richard; Schwenke, David

    2014-01-01

    Radiative emission from excited states of atoms and molecules can comprise a significant fraction of the total heat flux experienced by spacecraft during atmospheric entry at hypersonic speeds. For spacecraft with ablating heat shields, some of this radiative flux can be absorbed by molecular constituents in the boundary layer that are formed by the ablation process. Ab initio quantum mechanical calculations are carried out to predict the strengths of these emission and absorption processes. This talk will describe the methods used in these calculations using, as examples, the 4th positive emission bands of CO and the 1g+ 1u+ absorption in C3. The results of these calculations are being used as input to NASA radiation modeling codes like NeqAir, HARA and HyperRad.

  18. Mechanochemical models of processive molecular motors

    NASA Astrophysics Data System (ADS)

    Lan, Ganhui; Sun, Sean X.

    2012-05-01

    Motor proteins are the molecular engines powering the living cell. These nanometre-sized molecules convert chemical energy, both enthalpic and entropic, into useful mechanical work. High resolution single molecule experiments can now observe motor protein movement with increasing precision. The emerging data must be combined with structural and kinetic measurements to develop a quantitative mechanism. This article describes a modelling framework where quantitative understanding of motor behaviour can be developed based on the protein structure. The framework is applied to myosin motors, with emphasis on how synchrony between motor domains give rise to processive unidirectional movement. The modelling approach shows that the elasticity of protein domains are important in regulating motor function. Simple models of protein domain elasticity are presented. The framework can be generalized to other motor systems, or an ensemble of motors such as muscle contraction. Indeed, for hundreds of myosins, our framework can be reduced to the Huxely-Simmons description of muscle movement in the mean-field limit.

  19. Investigation of molecular penetration depth variation with SMBI fluxes

    NASA Astrophysics Data System (ADS)

    Zhou, Yu-Lin; Wang, Zhan-Hui; Xu, Min; Wang, Qi; Nie, Lin; Feng, Hao; Sun, Wei-Guo

    2016-09-01

    We study the molecular penetration depth variation with the SMBI fluxes. The molecular transport process and the penetration depth during SMBI with various injection velocities and densities are simulated and compared. It is found that the penetration depth of molecules strongly depends on the radial convective transport of SMBI and it increases with the increase of the injection velocity. The penetration depth does not vary much once the SMBI injection density is larger than a critical value due to the dramatic increase of the dissociation rate on the fueling path. An effective way to improve the SMBI penetration depth has been predicted, which is SMBI with a large radial injection velocity and a lower molecule injection density than the critical density. Project supported by the National Natural Science Foundation of China (Grant Nos. 11375053, 11575055, 11405022, and 11405112), the Chinese National Fusion Project for ITER (Grant Nos. 2013GB107001 and 2013GB112005), the International S&T Cooperation Program of China (Grant No. 2015DFA61760), and the Funds of the Youth Innovation Team of Science and Technology in Sichuan Province of China (Grant No. 2014TD0023).

  20. Ab initio investigation of benzene clusters: Molecular tailoring approach

    NASA Astrophysics Data System (ADS)

    Mahadevi, A. Subha; Rahalkar, Anuja P.; Gadre, Shridhar R.; Sastry, G. Narahari

    2010-10-01

    An exhaustive study on the clusters of benzene (Bz)n, n =2-8, at MP2/6-31++G∗∗ level of theory is reported. The relative strengths of CH-π and π-π interactions in these aggregates are examined, which eventually govern the pattern of cluster formation. A linear scaling method, viz., molecular tailoring approach (MTA), is efficiently employed for studying the energetics and growth patterns of benzene clusters consisting up to eight benzene (Bz) units. Accuracy of MTA-based calculations is appraised by performing the corresponding standard calculations wherever possible, i.e., up to tetramers. For benzene tetramers, the error introduced in energy is of the order of 0.1 mH (˜0.06 kcal/mol). Although for higher clusters the error may build up, further corrections based on many-body interaction energy analysis substantially reduce the error in the MTA-estimate. This is demonstrated for a prototypical case of benzene hexamer. A systematic way of building up a cluster of n monomers (n-mer) which employs molecular electrostatic potential of an (n -1)-mer is illustrated. The trends obtained using MTA method are essentially identical to those of the standard methods in terms of structure and energy. In summary, this study clearly brings out the possibility of effecting such large calculations, which are not possible conventionally, by the use of MTA without a significant loss of accuracy.

  1. Optical investigation of molecular structure of sophisticated materials for photonics

    NASA Astrophysics Data System (ADS)

    Gnyba, Marcin; Keraenen, Mikko

    2003-10-01

    Permanent development of photonics stimulates a searching for new materials, which have better optical, mechanical and electrical properties. One of the new classes of materials with large application and development potential are hybrid polymers, synthesized in sol-gel technology. Thanks to incorporation of organic components into an in organic network, a combination of advantages of both class of materials became available. Properties of hybrids may be formed in wide range. These materials can be used in photonics to produce planar waveguides, lenses, Bragg gratings and components for integrated optics. Moreover, dielectric layers, coatings and packaging are made from hybrids. Additionally, research to apply them in optical fiber sensors (including bio-sensors) and solid state lasers is underway. However, to obtain a high quality product, a strict control of its molecular structure must be ensured. This is a very difficult task, because of a sophisticated structure of hybrid polymers. To address these problems, optical, non-destructive measurement techniques such as Raman and infrared spectroscopy were used. They are compementary methods, so their simultaneous application, as it was shown in this paper, can significantly increase the amoung of information about molecular structure of materials and process of their synthesis.

  2. Applying Machine Trust Models to Forensic Investigations

    NASA Astrophysics Data System (ADS)

    Wojcik, Marika; Venter, Hein; Eloff, Jan; Olivier, Martin

    Digital forensics involves the identification, preservation, analysis and presentation of electronic evidence for use in legal proceedings. In the presence of contradictory evidence, forensic investigators need a means to determine which evidence can be trusted. This is particularly true in a trust model environment where computerised agents may make trust-based decisions that influence interactions within the system. This paper focuses on the analysis of evidence in trust-based environments and the determination of the degree to which evidence can be trusted. The trust model proposed in this work may be implemented in a tool for conducting trust-based forensic investigations. The model takes into account the trust environment and parameters that influence interactions in a computer network being investigated. Also, it allows for crimes to be reenacted to create more substantial evidentiary proof.

  3. In situ real-time spectroscopic ellipsometry measurement for the investigation of molecular orientation in organic amorphous multilayer structures

    NASA Astrophysics Data System (ADS)

    Yokoyama, Daisuke; Adachi, Chihaya

    2010-06-01

    To investigate molecular orientation in organic amorphous films, in situ real-time spectroscopic ellipsometry measurements were performed during vacuum deposition. Three materials with different molecular shapes were adopted to confirm the generality of the molecular orientation. In all three cases, more than 200 000 values for the ellipsometric parameters measured during deposition were well simulated simultaneously over the entire spectral range and measurement period using a simple model where the films possessed homogeneous optical anisotropy. This demonstrated the homogeneity of the molecular orientation in the direction of film thickness. The molecular orientation can be controlled by the substrate temperature even in multilayer structures. It is also demonstrated that a "multilayer structure" can be fabricated using only one material, where each layer has different optical and electrical properties.

  4. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    NASA Astrophysics Data System (ADS)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    ) experience with methods of protein purification; (iii) incorporation of appropriate controls into experiments; (iv) use of basic statistics in data analysis; (v) writing papers and grant proposals in accepted scientific style; (vi) peer review; (vii) oral presentation of results and proposals; and (viii) introduction to molecular modeling. Figure 1 illustrates the modular nature of the lab curriculum. Elements from each of the exercises can be separated and treated as stand-alone exercises, or combined into short or long projects. We have been able to offer the opportunity to use sophisticated molecular modeling in the final module through funding from an NSF-ILI grant. However, many of the benefits of the research proposal can be achieved with other computer programs, or even by literature survey alone. Figure 1.Design of project-based biochemistry laboratory. Modules (projects, or portions of projects) are indicated as boxes. Each of these can be treated independently, or used as part of a larger project. Solid lines indicate some suggested paths from one module to the next. The skills and knowledge required for protein purification and design are developed in three units: (i) an introduction to critical assays needed to monitor degree of purification, including an evaluation of assay parameters; (ii) partial purification by ion-exchange techniques; and (iii) preparation of a grant proposal on protein design by mutagenesis. Brief descriptions of each of these units follow, with experimental details of each project at the end of this paper. Assays for Lysozyme Activity and Protein Concentration (4 weeks) The assays mastered during the first unit are a necessary tool for determining the purity of the enzyme during the second unit on purification by ion exchange. These assays allow an introduction to the concept of specific activity (units of enzyme activity per milligram of total protein) as a measure of purity. In this first sequence, students learn a turbidimetric assay

  5. Model For Dense Molecular Cloud Cores

    NASA Technical Reports Server (NTRS)

    Doty, Steven D.; Neufeld, David A.

    1997-01-01

    We present a detailed theoretical model for the thermal balance, chemistry, and radiative transfer within quiescent dense molecular cloud cores that contain a central protostar. In the interior of such cores, we expect the dust and gas temperatures to be well coupled, while in the outer regions CO rotational emissions dominate the gas cooling and the predicted gas temperature lies significantly below the dust temperature. Large spatial variations in the gas temperature are expected to affect the gas phase chemistry dramatically; in particular, the predicted water abundance varies by more than a factor of 1000 within cloud cores that contain luminous protostars. Based upon our predictions for the thermal and chemical structure of cloud cores, we have constructed self-consistent radiative transfer models to compute the line strengths and line profiles for transitions of (12)CO, (13)CO, C(18)O, ortho- and para-H2(16)O, ortho- and para-H2(18)O, and O I. We carried out a general parameter study to determine the dependence of the model predictions upon the parameters assumed for the source. We expect many of the far-infrared and submillimeter rotational transitions of water to be detectable either in emission or absorption with the use of the Infrared Space Observatory (ISO) and the Submillimeter Wave Astronomy Satellite. Quiescent, radiatively heated hot cores are expected to show low-gain maser emission in the 183 GHz 3(sub 13)-2(sub 20) water line, such as has been observed toward several hot core regions using ground-based telescopes. We predict the (3)P(sub l) - (3)P(sub 2) fine-structure transition of atomic oxygen near 63 micron to be in strong absorption against the continuum for many sources. Our model can also account successfully for recent ISO observations of absorption in rovibrational transitions of water toward the source AFGL 2591.

  6. Challenges and novel approaches for investigating molecular mediation

    PubMed Central

    Richmond, R.C.; Hemani, G.; Tilling, K.; Davey Smith, G.; Relton, C.L.

    2016-01-01

    Understanding mediation is useful for identifying intermediates lying between an exposure and an outcome which, when intervened upon, will block (some or all of) the causal pathway between the exposure and outcome. Mediation approaches used in conventional epidemiology have been adapted to understanding the role of molecular intermediates in situations of high-dimensional omics data with varying degrees of success. In particular, the limitations of observational epidemiological study including confounding, reverse causation and measurement error can afflict conventional mediation approaches and may lead to incorrect conclusions regarding causal effects. Solutions to analysing mediation which overcome these problems include the use of instrumental variable methods such as Mendelian randomization, which may be applied to evaluate causality in increasingly complex networks of omics data. PMID:27439390

  7. [Mitochondrial diseases: molecular mechanisms, clinical presentations and diagnosis investigations].

    PubMed

    Auré, Karine; Jardel, Claude; Lombès, Anne

    2005-09-01

    Mitochondrial diseases are relatively common inherited metabolic diseases due to mitochondrial respiratory chain dysfunction. Their clinical presentation is extremely diverse, multisystemic or confined to a single tissue, sporadic or transmitted, by maternal or mendelian inheritance. The diagnosis of mitochondrial disorders is difficult. It is based upon several types of clues both clinical (family history, type of symptoms but also their association in syndromic presentation,...) and biological (alteration of the lactate metabolism, brain imaging, morphological alterations especially of muscle tissue). The diagnosis relies upon the demonstration of a defect of the respiratory chain activities and/or upon the identification of the underlying genetic alteration. Molecular diagnosis remains quite difficult and up to-date concerns essentially mitochondrial DNA mutations. On one hand, clinical and biological presentations as well as enzymatic defects lack specificity. On the other hand, candidate genes are very numerous and part of them are probably still unknown.

  8. A molecular dynamics investigation of surface reconstruction on magnetite (001)

    NASA Astrophysics Data System (ADS)

    Rustad, J. R.; Wasserman, E.; Felmy, A. R.

    1999-07-01

    Molecular dynamics calculations using analytical potential functions with polarizable oxygen ions have been used to identify a novel mode of reconstruction on the half-occupied tetrahedral layer termination of the magnetite (Fe 3O 4) (001) surface. In the proposed reconstruction, the twofold coordinated iron ion in the top monolayer rotates downward to occupy a vacant half-octahedral site in the plane of the second-layer iron ions. At the same time, half of the tetrahedral iron ions in the third iron layer are pushed upward to occupy an adjacent octahedral vacancy at the level of the second-layer iron ions. The other half of the third-layer iron ions remain roughly in their original positions. The proposed reconstruction is consistent with recent low-energy electron diffraction and X-ray photoelectron spectroscopy results. It also provides a compelling interpretation for the arrangement of atoms suggested by high-resolution scanning-tunneling microscopy studies.

  9. Final Report for Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Glotzer, Sharon C.

    2013-08-28

    In collaboration with researchers at Vanderbilt University, North Carolina State University, Princeton and Oakridge National Laboratory we developed multiscale modeling and simulation methods capable of modeling the synthesis, assembly, and operation of molecular electronics devices. Our role in this project included the development of coarse-grained molecular and mesoscale models and simulation methods capable of simulating the assembly of millions of organic conducting molecules and other molecular components into nanowires, crossbars, and other organized patterns.

  10. Homology Modeling and Molecular Docking for the Science Curriculum

    PubMed Central

    McDougal, Owen M.; Comia, Nic; Sambasivarao, S.V.; Remm, Andrew; Mallory, Chris; Oxford, Julia Thom; Maupin, C. Mark; Andersen, Tim

    2015-01-01

    DockoMatic 2.0 is a powerful open source software program (downloadable from sourceforge.net) that simplifies the exploration of computational biochemistry. This manuscript describes a practical tutorial for use in the undergraduate curriculum that introduces students to macromolecular structure creation, ligand binding calculations, and visualization of docking results. A student procedure is provided that illustrates use of DockoMatic to create a homology model for the amino propeptide region (223 amino acids with two disulfide bonds) of collagen α1 (XI), followed by molecular docking of the commercial drug Arixtra® to the homology model of the amino propeptide domain of collagen α1 (XI), and finally, analysis of the results of the docking experiment. The activities and supplemental materials described are intended to educate students in the use of computational tools to create and investigate homology models for other systems of interest and to train students to be proficient with molecular docking and analyzing results. The tutorial also serves as a foundation for investigators seeking to explore the viability of using computational biochemistry to study their receptor-ligand binding motifs. PMID:24376157

  11. Investigation of Chiral Molecular Micelles by NMR Spectroscopy and Molecular Dynamics Simulation

    PubMed Central

    Morris, Kevin F.; Billiot, Eugene J.; Billiot, Fereshteh H.; Lipkowitz, Kenny B.; Southerland, William M.; Fang, Yayin

    2013-01-01

    NMR spectroscopy and molecular dynamics (MD) simulation analyses of the chiral molecular micelles poly-(sodium undecyl-(L,L)-leucine-valine) (poly-SULV) and poly-(sodium undecyl-(L,L)- valine-leucine) (poly-(SUVL)) are reported. Both molecular micelles are used as chiral selectors in electrokinetic chromatography and each consists of covalently linked surfactant chains with chiral dipeptide headgroups. To provide experimental support for the structures from MD simulations, NOESY spectra were used to identify protons in close spatial proximity. Results from the NOESY analyses were then compared to radial distribution functions from MD simulations. In addition, the hydrodynamic radii of both molecular micelles were calculated from NMR-derived diffusion coefficients. Corresponding radii from the MD simulations were found to be in agreement with these experimental results. NMR diffusion experiments were also used to measure association constants for polar and non-polar binaphthyl analytes binding to both molecular micelles. Poly(SUVL) was found to bind the non-polar analyte enantiomers more strongly, while the more polar analyte enantiomers interacted more strongly with poly(SULV). MD simulations in tum showed that poly(SUL V) had a more open structure that gave greater access for water molecules to the dipeptide headgroup region. PMID:23991355

  12. Molecular Dynamics Investigation of the Substrate Binding Mechanism in Carboxylesterase

    SciTech Connect

    Chen, Qi; Luan, Zheng-Jiao; Cheng, Xiaolin; Xu, Jian-He

    2015-02-25

    A recombinant carboxylesterase, cloned from Pseudomonas putida and designated as rPPE, is capable of catalyzing the bioresolution of racemic 2-acetoxy-2-(2 -chlorophenyl)acetate (rac-AcO-CPA) with excellent (S)-enantioselectivity. Semi-rational design of the enzyme showed that the W187H variant could increase the activity by ~100-fold compared to the wild type (WT) enzyme. In this study, we performed all-atom molecular dynamics (MD) simulations of both apo-rPPE and rPPE in complex with (S)-AcO-CPA to gain insights into the origin of the increased catalysis in the W187H mutant. Moreover, our results show differential binding of (S)-AcO-CPA in the WT and W187H enzymes, especially the interactions of the substrate with the two active site residues Ser159 and His286. The replacement of Trp187 by His leads to considerable structural rearrangement in the active site of W187H. Unlike in the WT rPPE, the cap domain in the W187 mutant shows an open conformation in the simulations of both apo and substrate-bound enzymes. This open conformation exposes the catalytic triad to the solvent through a water accessible channel, which may facilitate the entry of the substrate and/or the exit of the product. Binding free energy calculations confirmed that the substrate binds more strongly in W187H than in WT. Based on these computational results, furthermore, we predicted that the mutations W187Y and D287G might also be able to increase the substrate binding, thus improve the enzyme s catalytic efficiency. Experimental binding and kinetic assays on W187Y and D287G show improved catalytic efficiency over WT, but not W187H. Contrary to our prediction, W187Y shows slightly decreased substrate binding coupled with a 100 fold increase in turn-over rate, while in D287G the substrate binding is 8 times stronger but with a slightly reduced turn-over rate. Finally, our work provides important molecular-level insights into the binding of the (S)-AcO-CPA substrate to carboxylesterase r

  13. Molecular Dynamics Investigation of the Substrate Binding Mechanism in Carboxylesterase

    DOE PAGES

    Chen, Qi; Luan, Zheng-Jiao; Cheng, Xiaolin; ...

    2015-02-25

    A recombinant carboxylesterase, cloned from Pseudomonas putida and designated as rPPE, is capable of catalyzing the bioresolution of racemic 2-acetoxy-2-(2 -chlorophenyl)acetate (rac-AcO-CPA) with excellent (S)-enantioselectivity. Semi-rational design of the enzyme showed that the W187H variant could increase the activity by ~100-fold compared to the wild type (WT) enzyme. In this study, we performed all-atom molecular dynamics (MD) simulations of both apo-rPPE and rPPE in complex with (S)-AcO-CPA to gain insights into the origin of the increased catalysis in the W187H mutant. Moreover, our results show differential binding of (S)-AcO-CPA in the WT and W187H enzymes, especially the interactions of themore » substrate with the two active site residues Ser159 and His286. The replacement of Trp187 by His leads to considerable structural rearrangement in the active site of W187H. Unlike in the WT rPPE, the cap domain in the W187 mutant shows an open conformation in the simulations of both apo and substrate-bound enzymes. This open conformation exposes the catalytic triad to the solvent through a water accessible channel, which may facilitate the entry of the substrate and/or the exit of the product. Binding free energy calculations confirmed that the substrate binds more strongly in W187H than in WT. Based on these computational results, furthermore, we predicted that the mutations W187Y and D287G might also be able to increase the substrate binding, thus improve the enzyme s catalytic efficiency. Experimental binding and kinetic assays on W187Y and D287G show improved catalytic efficiency over WT, but not W187H. Contrary to our prediction, W187Y shows slightly decreased substrate binding coupled with a 100 fold increase in turn-over rate, while in D287G the substrate binding is 8 times stronger but with a slightly reduced turn-over rate. Finally, our work provides important molecular-level insights into the binding of the (S)-AcO-CPA substrate to carboxylesterase r

  14. Investigation of the inclusions of puerarin and daidzin with beta-cyclodextrin by molecular dynamics simulation.

    PubMed

    Zhang, Haiyang; Feng, Wei; Li, Cong; Tan, Tianwei

    2010-04-15

    Puerarin and daidzin, two major isoflavonoids of Radix puerariae , are widely adopted in traditional Chinese medicine. Foundational aspects related to separating the two compounds are essential to develop a more economical purification process. Inclusion models of the two compounds with beta-cyclodextrin (beta-CD) have been investigated by molecular dynamics simulation. Computational results reveal that both puerarin and daidzin can induce a conformational change of beta-CD, which is compressed in one direction and stretched in the other. The effect of solvent and media on the conformational change of beta-CD and the movement of guest molecules inside the cavity has been investigated. Furthermore, hydrogen bonding interactions have been analyzed, and the results have been utilized for the explanation of separating puerarin from daidzin.

  15. Molecular modeling of crystalline alkylthiophene oligomers and polymers.

    PubMed

    Moreno, Margherita; Casalegno, Mosè; Raos, Guido; Meille, Stefano V; Po, Riccardo

    2010-02-04

    We present the results of a thorough molecular modeling study of several alkylthiophene-based oligomers and polymers. In particular, we consider two polymers whose limit-ordered crystal structures have been recently reported by our group, on the basis of powder X-ray data analysis: poly(3-(S)-2-methylbutylthiophene) (P3MBT) and form I' of poly(3-butylthiophene) (P3BT). We first describe the development of a series general purpose force fields for the simulation of these and related systems. The force fields incorporate the results of ab initio calculations of the bond torsion energies of selected oligomers and differ in the set of atomic charges used to represent the electrostatic interactions. We then present the results of an extensive validation of these force fields, by means of molecular mechanics (MM) energy minimizations and molecular dynamics (MD) simulations of the crystal structures of these oligomers and polymers. While our "best" force field does not outperform the others on each of the investigated systems, it provides a balanced description of their overall structure and energetics. Finally, our MM minimizations and MD simulations confirm that the reported crystal structures of P3MBT and P3BT are stable and correspond to well-defined energetic minima. The room-temperature MD simulations reveal a certain degree of side-chain disorder, even in our virtually defect-free polymer crystal models.

  16. Dynamic Wetting on Graphene-Coated Surface: Molecular Dynamics Investigation

    NASA Astrophysics Data System (ADS)

    Hung, Shih-Wei; Shiomi, Junichiro

    2015-11-01

    Wettability of graphene-coated surface gained significant attention recently due to discussion on the ``transparency'' (whether the wetting characteristics follow that of graphene or the underlying surface) and practical applications of graphene. In terms of static contact angle, the wettability of graphene-coated surfaces have been widely studied by experiments, simulations, and theory in recent years. However, the studies of dynamic wetting on graphene-coated surfaces are limited. In the present study, molecular dynamics simulation was performed to study the dynamic wetting of water droplet on graphene-coated surfaces from a microscopic point of view. The results show that the degree of similarity between the spreading behavior on graphene-coated surface and that on pure graphene (or that on the underlying surface) depends on time, i.e. how nonequilibrium the interface dynamics is. We also found that this feature can be altered by introducing defects into graphene. The work is partially supported by Grant-in-Aid for JSPS Fellows 26-04364 and JST CREST.

  17. A First-principles Molecular Dynamics Investigation of Superionic Conductivity

    NASA Astrophysics Data System (ADS)

    Wood, Brandon; Marzari, Nicola

    2007-03-01

    Superionic materials---solids with liquid-like transport properties---have found widespread use in a variety of applications in fuel cells, switches, sensors, and batteries. However, reasons for fast-ion conduction in such materials, as well as the specific atomistic mechanisms involved, remain ill understood. Our work uses first-principles molecular dynamics to illuminate the mechanisms, pathways, and motivations for superionic conductivity in two materials representing different classes of ion conductors: α-AgI, an archetypal Type-I superionic; and CsHSO4, an anhydrous solid-state electrolyte candidate for hydrogen fuel cells. For α-AgI, we trace common pathways for silver ion conduction and discuss how a chemical signature in the electronic structure relates to enhanced silver ion mobility. We also characterize the dynamical lattice structure in the superionic phase and present the likely motivations for its existence. For CsHSO4, we isolate the dominant atomistic mechanisms involved in superprotonic conduction and discuss the effect of correlated diffusive events in enhancing proton transport. We also offer a detailed description of the dynamics of the hydrogen bond network topology in the course of proton diffusion and discuss the relevance of atomistic processes with competing timescales in facilitating proton transport.

  18. Investigation of the kinetic model equations.

    PubMed

    Liu, Sha; Zhong, Chengwen

    2014-03-01

    Currently the Boltzmann equation and its model equations are widely used in numerical predictions for dilute gas flows. The nonlinear integro-differential Boltzmann equation is the fundamental equation in the kinetic theory of dilute monatomic gases. By replacing the nonlinear fivefold collision integral term by a nonlinear relaxation term, its model equations such as the famous Bhatnagar-Gross-Krook (BGK) equation are mathematically simple. Since the computational cost of solving model equations is much less than that of solving the full Boltzmann equation, the model equations are widely used in predicting rarefied flows, multiphase flows, chemical flows, and turbulent flows although their predictions are only qualitatively right for highly nonequilibrium flows in transitional regime. In this paper the differences between the Boltzmann equation and its model equations are investigated aiming at giving guidelines for the further development of kinetic models. By comparing the Boltzmann equation and its model equations using test cases with different nonequilibrium types, two factors (the information held by nonequilibrium moments and the different relaxation rates of high- and low-speed molecules) are found useful for adjusting the behaviors of modeled collision terms in kinetic regime. The usefulness of these two factors are confirmed by a generalized model collision term derived from a mathematical relation between the Boltzmann equation and BGK equation that is also derived in this paper. After the analysis of the difference between the Boltzmann equation and the BGK equation, an attempt at approximating the collision term is proposed.

  19. ATOMIC AND MOLECULAR PHYSICS: Modelling of a DNA packaging motor

    NASA Astrophysics Data System (ADS)

    Qian, Jun; Xie, Ping; Xue, Xiao-Guang; Wang, Peng-Ye

    2009-11-01

    During the assembly of many viruses, a powerful molecular motor packages the genome into a preassembled capsid. The Bacillus subtilis phage phi29 is an excellent model system to investigate the DNA packaging mechanism because of its highly efficient in vitro DNA packaging activity and the development of a single-molecule packaging assay. Here we make use of structural and biochemical experimental data to build a physical model of DNA packaging by the phi29 DNA packaging motor. Based on the model, various dynamic behaviours such as the packaging rate, pause frequency and slip frequency under different ATP concentrations, ADP concentrations, external loads as well as capsid fillings are studied by using Monte Carlo simulation. Good agreement is obtained between the simulated and available experimental results. Moreover, we make testable predictions that should guide future experiments related to motor function.

  20. Investigation of multilayer painting by means of molecular spectroscopy

    NASA Astrophysics Data System (ADS)

    Kadikova, I. F.; Grigorieva, I. A.

    2016-12-01

    The study of paintings' layer structure under microscope was implemented in the early XX century; since that time method of cross-section preparation as well as composition of embedded materials changed and capabilities of optical microscopy broadened. Nevertheless, until recently cross-sections were prepared only for analysis of paintings' layer-specific structure, morphological and technological features, tracks of restoration treatments. Examination of chemical composition required additional sampling as well as division of these samples layer by layer in order to determine pigments and binding media; these procedures didn't always lead to proper results. Micro-Raman and micro-FTIR spectroscopy allow carrying out investigation of painting cross-sections without any additional preliminary sampling; this is shown on example of investigation of a number of paintings.

  1. Molecular self-assembly for biological investigations and nanoscale lithography

    NASA Astrophysics Data System (ADS)

    Cheunkar, Sarawut

    Small, diffusible molecules when recognized by their binding partners, such as proteins and antibodies, trigger enzymatic activity, cell communication, and immune response. Progress in analytical methods enabling detection, characterization, and visualization of biological dynamics at the molecular level will advance our exploration of complex biological systems. In this dissertation, analytical platforms were fabricated to capture membrane-associated receptors, which are essential proteins in cell signaling pathways. The neurotransmitter serotonin and its biological precursor were immobilized on gold substrates coated with self-assembled monolayers (SAMs) of oligo(ethylene glycol)alkanethiols and their reactive derivatives. The SAM-coated substrates present the biologically selective affinity of immobilized molecules to target native membrane-associated receptors. These substrates were also tested for biospecificity using antibodies. In addition, small-molecule-functionalized platforms, expressing neurotransmitter pharmacophores, were employed to examine kinetic interactions between G-protein-coupled receptors and their associated neurotransmitters. The binding interactions were monitored using a quartz crystal microbalance equipped with liquid-flow injection. The interaction kinetics of G-protein-coupled serotonin 1A receptor and 5-hydroxytyptophan-functionalized surfaces were studied in a real-time, label-free environment. Key binding parameters, such as equilibrium dissociation constants, binding rate constants, and dissociative half-life, were extracted. These parameters are critical for understanding and comparing biomolecular interactions in modern biomedical research. By integrating self-assembly, surface functionalization, and nanofabrication, small-molecule microarrays were created for high-throughput screening. A hybrid soft-lithography, called microcontact insertion printing, was used to pattern small molecules at the dilute scales necessary for highly

  2. An Analytical Model for Molecular Propagation in Nanocommunication via Filaments Using Relay-Enabled Nodes.

    PubMed

    Darchinimaragheh, Kamaloddin; Alfa, Attahiru S

    2015-12-01

    Molecular communication is a nanoscale communication method in which information is encoded in molecules. Molecular communication using microtubules in free space is one of the realistic scenarios proposed for this type of nanocommunication. Based on this technique, molecular communication via filaments using nano-relays is proposed in this paper to improve the performance of the system in terms of delay and bit error probability. An analytical model using jump diffusion processes is proposed for molecular propagation in this scenario. It is shown that the proposed mathematical model is capable of tracking molecular propagation in molecular communication via filaments using nano-relays. Also, the model is used to investigate effects of different parameters on delay and bit error probability.

  3. Cellular and molecular investigations of the adhesion and mechanics of Listeria monocytogenes

    NASA Astrophysics Data System (ADS)

    Eskhan, Asma Omar

    adhesion and mechanics are correlated. To test this hypothesis, nonadhesive and adhesive models of contact mechanics were used to estimate Young's moduli. Our results indicated that the nonadhesive model of contact mechanics estimated 18 % more rigid bacterial cells. Our results thus point to the importance of considering molecular details when investigating bacterial adhesion and mechanics.

  4. Modeling Nanocomposites for Molecular Dynamics (MD) Simulations

    DTIC Science & Technology

    2015-01-01

    Maximum 200 Words) The minimum energy configuration for Molecular Dynamics (MD) simulations is found for a carbon nanotube (CNT)/polymer...Carbon Nanotubes (CNTs), Molecular Dynamics Simulations 15. NUMBER OF PAGES 18 16. PRICE CODE 17. SECURITY CLASSIFICATION OF REPORT...fiber composites have shown success in improving mechanical properties. Carbon nanotube (CNT)-based nanocomposites have been studied for

  5. Biological networks 101: computational modeling for molecular biologists.

    PubMed

    Scholma, Jetse; Schivo, Stefano; Urquidi Camacho, Ricardo A; van de Pol, Jaco; Karperien, Marcel; Post, Janine N

    2014-01-01

    Computational modeling of biological networks permits the comprehensive analysis of cells and tissues to define molecular phenotypes and novel hypotheses. Although a large number of software tools have been developed, the versatility of these tools is limited by mathematical complexities that prevent their broad adoption and effective use by molecular biologists. This study clarifies the basic aspects of molecular modeling, how to convert data into useful input, as well as the number of time points and molecular parameters that should be considered for molecular regulatory models with both explanatory and predictive potential. We illustrate the necessary experimental preconditions for converting data into a computational model of network dynamics. This model requires neither a thorough background in mathematics nor precise data on intracellular concentrations, binding affinities or reaction kinetics. Finally, we show how an interactive model of crosstalk between signal transduction pathways in primary human articular chondrocytes allows insight into processes that regulate gene expression.

  6. Computational Modeling of Cell Electroporation and Molecular Delivery.

    NASA Astrophysics Data System (ADS)

    Lin, Hao; Li, Jianbo

    2007-11-01

    Electroporation is an elegant means to gain access to the cytoplasm, and to deliver molecules into the cell while simultaneously maintaining viability and functionality. In this technique, an applied electric pulse transiently permeabilizes the cell membrane, through which biologically active agents such as DNA, RNA, and amino acids can enter the cell, and to perform tasks such as gene and cancer therapy. Current electroporation technologies fall short of desired efficiency and reliability, in part due to the lack of a good understanding in the pertinent fundamental processes. In this work, we use computational modeling to investigate electroporation-mediated molecular delivery, with a focus on the transport mechanisms long ignored in previous studies. By coupling the Smoluchowski equation governing membrane permeabilization with an electrohydrodynamic model, major aspects including electrophoresis, diffusion, and membrane deformation are investigated. Specifically, the effect of electrical parameters such as field strength, duration, and intra-/extra-cellular electrical conductivity on transport efficacy will be quantified. The eventual objective of this study is to optimize molecular delivery via simultaneously increasing transport and minimizing cell damage due to field exposure.

  7. Physics Beyond the Standard Model from Molecular Hydrogen Spectroscopy

    NASA Astrophysics Data System (ADS)

    Ubachs, Wim; Salumbides, Edcel John; Bagdonaite, Julija

    2015-06-01

    The spectrum of molecular hydrogen can be measured in the laboratory to very high precision using advanced laser and molecular beam techniques, as well as frequency-comb based calibration [1,2]. The quantum level structure of this smallest neutral molecule can now be calculated to very high precision, based on a very accurate (10-15 precision) Born-Oppenheimer potential [3] and including subtle non-adiabatic, relativistic and quantum electrodynamic effects [4]. Comparison between theory and experiment yields a test of QED, and in fact of the Standard Model of Physics, since the weak, strong and gravitational forces have a negligible effect. Even fifth forces beyond the Standard Model can be searched for [5]. Astronomical observation of molecular hydrogen spectra, using the largest telescopes on Earth and in space, may reveal possible variations of fundamental constants on a cosmological time scale [6]. A study has been performed at a 'look-back' time of 12.5 billion years [7]. In addition the possible dependence of a fundamental constant on a gravitational field has been investigated from observation of molecular hydrogen in the photospheres of white dwarfs [8]. The latter involves a test of the Einsteins equivalence principle. [1] E.J. Salumbides et al., Phys. Rev. Lett. 107, 143005 (2011). [2] G. Dickenson et al., Phys. Rev. Lett. 110, 193601 (2013). [3] K. Pachucki, Phys. Rev. A82, 032509 (2010). [4] J. Komasa et al., J. Chem. Theory Comp. 7, 3105 (2011). [5] E.J. Salumbides et al., Phys. Rev. D87, 112008 (2013). [6] F. van Weerdenburg et al., Phys. Rev. Lett. 106, 180802 (2011). [7] J. Badonaite et al., Phys. Rev. Lett. 114, 071301 (2015). [8] J. Bagdonaite et al., Phys. Rev. Lett. 113, 123002 (2014).

  8. Cloning Yeast Actin cDNA Leads to an Investigative Approach for the Molecular Biology Laboratory

    ERIC Educational Resources Information Center

    Black, Michael W.; Tuan, Alice; Jonasson, Erin

    2008-01-01

    The emergence of molecular tools in multiple disciplines has elevated the importance of undergraduate laboratory courses that train students in molecular biology techniques. Although it would also be desirable to provide students with opportunities to apply these techniques in an investigative manner, this is generally not possible in the…

  9. Digital Learning Material for Model Building in Molecular Biology

    ERIC Educational Resources Information Center

    Aegerter-Wilmsen, Tinri; Janssen, Fred; Hartog, Rob; Bisseling, Ton

    2005-01-01

    Building models to describe processes forms an essential part of molecular biology research. However, in molecular biology curricula little attention is generally being paid to the development of this skill. In order to provide students the opportunity to improve their model building skills, we decided to develop a number of digital cases about…

  10. Investigation and Modeling of Cranberry Weather Stress.

    NASA Astrophysics Data System (ADS)

    Croft, Paul Joseph

    Cranberry bog weather conditions and weather-related stress were investigated for development of crop yield prediction models and models to predict daily weather conditions in the bog. Field investigations and data gathering were completed at the Rutgers University Blueberry/Cranberry Research Center experimental bogs in Chatsworth, New Jersey. Study indicated that although cranberries generally exhibit little or no stomatal response to changing atmospheric conditions, the evaluation of weather-related stress could be accomplished via use of micrometeorological data. Definition of weather -related stress was made by establishing critical thresholds of the frequencies of occurrence, and magnitudes of, temperature and precipitation in the bog based on values determined by a review of the literature and a grower questionnaire. Stress frequencies were correlated with cranberry yield to develop predictive models based on the previous season's yield, prior season data, prior and current season data, current season data; and prior and current season data through July 31 of the current season. The predictive ability of the prior season models was best and could be used in crop planning and production. Further examination of bog micrometeorological data permitted the isolation of those weather conditions conducive to cranberry scald and allowed for the institution of a pilot scald advisory program during the 1991 season. The micrometeorological data from the bog was also used to develop models to predict daily canopy temperature and precipitation, based on upper air data, for grower use. Models were developed for each month for maximum and minimum temperatures and for precipitation and generally performed well. The modeling of bog weather conditions is an important first step toward daily prediction of cranberry weather-related stress.

  11. Modeling propagation of coherent optical pulses through molecular vapor

    SciTech Connect

    Shore, B.W.; Eberly, J.H.

    1982-01-01

    Results of modeling the mutual coupling of coherent molecular response and coherent optical pulses during propagation are described. The propagation is treated numerically, with particular emphasis on both continuum and discrete behavior associated with the quasicontinuum model.

  12. Molecular modeling of PMR-15 polyimide

    NASA Astrophysics Data System (ADS)

    Kokkada Ravindranath, Pruthul

    PMR-15 polyimide is a polymer that is used as a matrix in composites. These composites with PMR-15 matrices are called advanced polymer matrix composite that is abundantly used in the aerospace and electronics industries because of its high temperature resistivity. Apart from having high temperature sustainability, PMR-15 composites also display good thermal-oxidative stability, mechanical properties, processability and low costs, which makes it a suitable material for manufacturing aircraft structures. PMR-15 uses the reverse Diels-Alder (RDA) method for crosslinking which provides it with the groundwork for its distinctive thermal stability and a range of 280--300°C use temperature. Regardless of such desirable properties, this material has a number of limitations that compromises its application on a large scale basis. PMR-15 composites has been known to be very vulnerable to micro-cracking at inter and intra-laminar cracking. But the major factor that hinders its demand is PMR-15's carcinogenic constituent, methylene dianilineme (MDA), also a liver toxin. The necessity of providing a safe working environment during its production adds up to the cost of this material. In this study, Molecular Dynamics and Energy Minimization techniques are utilized to simulate a structure of PMR-15 at a given density of 1.324 g/cc and an attempt to recreate the polyimide to reduce the number of experimental testing and hence subdue the health hazards as well as the cost involved in its production. Even though this study does not involve in validating any mechanical properties of the model, it could be used in future for the validation of its properties and further testing for different properties like aging, microcracking, creep etc.

  13. Molecular investigation on the interaction of spermine with proteinase K by multispectroscopic techniques and molecular simulation studies.

    PubMed

    Hosseini-Koupaei, Mansoore; Shareghi, Behzad; Saboury, Ali Akbar; Davar, Fateme

    2017-01-01

    The alteration in structure, function and stability of proteinase K in the presence of spermine was investigated using spectroscopic methods and simulation techniques. The stability and enzyme activity of proteinase K-spermine complex were significantly enhanced as compared to that of the pure enzyme. The increase in the value of Vmax and the catalytic efficiency of Proteinase K in presence of spermine confirmed that the polyamine could bring the enzyme hyperactivation. UV-vis spectroscopy, intrinsic fluorescence and circular dichroism methods demonstrated that the binding of spermine changed the microenvironment and structure of proteinase K. The fluorescence studies, showing that spermine quenched the intensity of proteinase K with static mechanism. Thermodynamic parameters analysis suggested that hydrogen bond and van der Waals forces play a key role in complex stability which is in agreement with modeling studies. The CD spectra represented the secondary structure alteration of proteinase K with an increase in α-helicity and a decrease in β-sheet of proteinase K upon spermine conjugation. The molecular simulation results proposed that spermine could interact with proteinase K spontaneously at single binding site, which is in agreement with spectroscopic results. This agreement between experimental and theoretical results may be a worth method for protein-ligand complex studies.

  14. Modeling Complex Workflow in Molecular Diagnostics

    PubMed Central

    Gomah, Mohamed E.; Turley, James P.; Lu, Huimin; Jones, Dan

    2010-01-01

    One of the hurdles to achieving personalized medicine has been implementing the laboratory processes for performing and reporting complex molecular tests. The rapidly changing test rosters and complex analysis platforms in molecular diagnostics have meant that many clinical laboratories still use labor-intensive manual processing and testing without the level of automation seen in high-volume chemistry and hematology testing. We provide here a discussion of design requirements and the results of implementation of a suite of lab management tools that incorporate the many elements required for use of molecular diagnostics in personalized medicine, particularly in cancer. These applications provide the functionality required for sample accessioning and tracking, material generation, and testing that are particular to the evolving needs of individualized molecular diagnostics. On implementation, the applications described here resulted in improvements in the turn-around time for reporting of more complex molecular test sets, and significant changes in the workflow. Therefore, careful mapping of workflow can permit design of software applications that simplify even the complex demands of specialized molecular testing. By incorporating design features for order review, software tools can permit a more personalized approach to sample handling and test selection without compromising efficiency. PMID:20007844

  15. Molecular connectivity indices for modeling the critical micelle concentration of cationic (chloride) Gemini surfactants.

    PubMed

    Mozrzymas, Anna

    2017-01-01

    The molecular connectivity indices were used to derive the simple model relating the critical micelle concentration of cationic (chloride) gemini surfactants to their structure. One index was selected as the best to describe the effect of the structure of investigated compounds on critical micelle concentration consistent with the experimental results. This index encodes the information about molecular size, the branches, and also the information about heteroatoms. The selected model can be helpful in designing novel chloride gemini surfactants.

  16. Accelerating molecular modeling applications with graphics processors.

    PubMed

    Stone, John E; Phillips, James C; Freddolino, Peter L; Hardy, David J; Trabuco, Leonardo G; Schulten, Klaus

    2007-12-01

    Molecular mechanics simulations offer a computational approach to study the behavior of biomolecules at atomic detail, but such simulations are limited in size and timescale by the available computing resources. State-of-the-art graphics processing units (GPUs) can perform over 500 billion arithmetic operations per second, a tremendous computational resource that can now be utilized for general purpose computing as a result of recent advances in GPU hardware and software architecture. In this article, an overview of recent advances in programmable GPUs is presented, with an emphasis on their application to molecular mechanics simulations and the programming techniques required to obtain optimal performance in these cases. We demonstrate the use of GPUs for the calculation of long-range electrostatics and nonbonded forces for molecular dynamics simulations, where GPU-based calculations are typically 10-100 times faster than heavily optimized CPU-based implementations. The application of GPU acceleration to biomolecular simulation is also demonstrated through the use of GPU-accelerated Coulomb-based ion placement and calculation of time-averaged potentials from molecular dynamics trajectories. A novel approximation to Coulomb potential calculation, the multilevel summation method, is introduced and compared with direct Coulomb summation. In light of the performance obtained for this set of calculations, future applications of graphics processors to molecular dynamics simulations are discussed.

  17. Molecular dynamics investigation of nanoscale substrate topography and its interaction with liquids

    NASA Astrophysics Data System (ADS)

    Cordeiro Rodrigues, Jhonatam

    Nanotechnology has been presenting successful applications in several areas. However, experimentation with nanoscale materials is costly and limited in analysis capability. This research investigates the use of molecular dynamics (MD) simulations to model and study nanomaterials and manufacturing processes. MD simulations are employed to reduce cost, optimize design, increase productivity and allow for the investigation of material interactions not yet observable through experimentation. This work investigates the interaction of water with substrates at the nanoscale. The effect of temperature, droplet impingement velocities and size, as well as substrate material, are investigated at the nanoscale. Several substrate topography designs were modeled to reveal their influence on the wettability of the substrate. Nanoscale gold and silicon substrates are more hydrophilic at higher temperatures than at room temperature. The reduction in droplet diameter increases its wettability. High impingement velocity of droplets does not influence final wettability of substrates but induces higher diffusion rates of droplets in a heated environment. Droplets deposited over a gradient of surface exposure presents spontaneous movement. The Leidenfrost effect was investigated at the nanoscale. Droplets of 4 and 10nm in diameter presented behaviors pertinent to the Leidenfrost effect at 373K, significantly lower than at micro scale and of potential impact to the field. Topographical features were manipulated using superhydrophobic coating resulting in micro whiskers. Nanoimprint lithography (NIL) was used to manufacture substrate topographies at the nanoscale. Water droplets were deposited on the substrates and their wettability was measured using droplet contact angles. Lower surface area exposure resulted in higher contact angles. The experimental relationships between surface topography and substrate wettability were used to validate the insights gained from MD simulations for

  18. Raman spectroscopy based investigation of molecular changes associated with an early stage of dengue virus infection

    NASA Astrophysics Data System (ADS)

    Bilal, Maria; Bilal, Muhammad; Saleem, Muhammad; Khurram, Muhammad; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, Mushtaq; Shahzada, Shaista; Ullah Khan, Ehsan

    2017-04-01

    Raman spectroscopy based investigations of the molecular changes associated with an early stage of dengue virus infection (DENV) using a partial least squares (PLS) regression model is presented. This study is based on non-structural protein 1 (NS1) which appears after three days of DENV infection. In total, 39 blood sera samples were collected and divided into two groups. The control group contained samples which were the negative for NS1 and antibodies and the positive group contained those samples in which NS1 is positive and antibodies were negative. Out of 39 samples, 29 Raman spectra were used for the model development while the remaining 10 were kept hidden for blind testing of the model. PLS regression yielded a vector of regression coefficients as a function of Raman shift, which were analyzed. Cytokines in the region 775–875 cm‑1, lectins at 1003, 1238, 1340, 1449 and 1672 cm‑1, DNA in the region 1040–1140 cm‑1 and alpha and beta structures of proteins in the region 933–967 cm‑1 have been identified in the regression vector for their role in an early stage of DENV infection. Validity of the model was established by its R-square value of 0.891. Sensitivity, specificity and accuracy were 100% each and the area under the receiver operator characteristic curve was found to be 1.

  19. The role of molecular epidemiology in contact investigations: a US perspective.

    PubMed

    Daley, C L; Kawamura, L M

    2003-12-01

    Preventing tuberculosis (TB) transmission through treatment of active cases and contact investigation is the highest priority of TB control programs in the United States. The role of contact investigation is becoming increasingly important as the number of TB cases declines nationally. However, the effectiveness of contact investigation has been difficult to assess because, prior to the availability of molecular genotyping techniques, levels of transmission were crudely measurable. Epidemiological links within and outside the traditional concentric circle approach are limited by the quality of the contact investigation, the skill and knowledge of the investigator and the information provided by the patient. Molecular epidemiology has added a new dimension by enabling the recognition of unsuspected transmission, likely locations of transmission, and quantification of the extent of transmission that is occurring within a given population. In the future, as real-time genotyping becomes more available, the role of molecular epidemiology is likely to expand.

  20. Investigation of Interference Models for RFID Systems.

    PubMed

    Zhang, Linchao; Ferrero, Renato; Gandino, Filippo; Rebaudengo, Maurizio

    2016-02-04

    The reader-to-reader collision in an RFID system is a challenging problem for communications technology. In order to model the interference between RFID readers, different interference models have been proposed, mainly based on two approaches: single and additive interference. The former only considers the interference from one reader within a certain range, whereas the latter takes into account the sum of all of the simultaneous interferences in order to emulate a more realistic behavior. Although the difference between the two approaches has been theoretically analyzed in previous research, their effects on the estimated performance of the reader-to-reader anti-collision protocols have not yet been investigated. In this paper, the influence of the interference model on the anti-collision protocols is studied by simulating a representative state-of-the-art protocol. The results presented in this paper highlight that the use of additive models, although more computationally intensive, is mandatory to improve the performance of anti-collision protocols.

  1. Fluctuation theorem for the flashing ratchet model of molecular motors

    NASA Astrophysics Data System (ADS)

    Lacoste, D.; Mallick, K.

    2009-08-01

    Molecular motors convert chemical energy derived from the hydrolysis of adenosine triphosphate (ATP) into mechanical energy. A well-studied model of a molecular motor is the flashing ratchet model. We show that this model exhibits a fluctuation relation known as the Gallavotti-Cohen symmetry. Our study highlights the fact that the symmetry is present only if the chemical and mechanical degrees of freedom are both included in the description.

  2. Fluctuation theorem for the flashing ratchet model of molecular motors.

    PubMed

    Lacoste, D; Mallick, K

    2009-08-01

    Molecular motors convert chemical energy derived from the hydrolysis of adenosine triphosphate (ATP) into mechanical energy. A well-studied model of a molecular motor is the flashing ratchet model. We show that this model exhibits a fluctuation relation known as the Gallavotti-Cohen symmetry. Our study highlights the fact that the symmetry is present only if the chemical and mechanical degrees of freedom are both included in the description.

  3. Molecular Dynamics implementation of BN2D or 'Mercedes Benz' water model

    NASA Astrophysics Data System (ADS)

    Scukins, Arturs; Bardik, Vitaliy; Pavlov, Evgen; Nerukh, Dmitry

    2015-05-01

    Two-dimensional 'Mercedes Benz' (MB) or BN2D water model (Naim, 1971) is implemented in Molecular Dynamics. It is known that the MB model can capture abnormal properties of real water (high heat capacity, minima of pressure and isothermal compressibility, negative thermal expansion coefficient) (Silverstein et al., 1998). In this work formulas for calculating the thermodynamic, structural and dynamic properties in microcanonical (NVE) and isothermal-isobaric (NPT) ensembles for the model from Molecular Dynamics simulation are derived and verified against known Monte Carlo results. The convergence of the thermodynamic properties and the system's numerical stability are investigated. The results qualitatively reproduce the peculiarities of real water making the model a visually convenient tool that also requires less computational resources, thus allowing simulations of large (hydrodynamic scale) molecular systems. We provide the open source code written in C/C++ for the BN2D water model implementation using Molecular Dynamics.

  4. Modelling the global tropospheric molecular hydrogen cycle

    NASA Astrophysics Data System (ADS)

    Pieterse, G.

    2013-01-01

    Would urban air quality and climate improve if we replaced the fossil fuels by molecular hydrogen (H2) as an energy carrier? A quantitative answer to this question requires a thorough understanding of the current role of H2 in the Earth’s atmosphere. On its own, H2 does not impact climate, as for example carbon dioxide or methane. However, increasing levels of H2 in the stratosphere can lead to increased ozone loss due to the formation of polar stratospheric clouds. Additionally, the atmospheric lifetime of methane could increase because both H2 and methane are removed by photochemical oxidation with the hydroxyl radical. Consequently, the lifetime of the strong greenhouse gas methane could be prolonged. During the last two decades, more and more experimental data have become available to put tighter constraints on the different sources and sinks that contribute to the global H2 cycle. However, the main removal process, dry deposition due to microbial/enzymatic decomposition of H2 in the soils, still has a rather large uncertainty between 40-99 Tg/yr globally. This is a highly uncertain number compared to the estimated overall amount of 136-166 Tg present in the troposphere. The photochemical removal of H2 from the atmosphere is estimated at 14-24 Tg/yr. Together with the estimates for the burden and dry deposition, this implies a tropospheric lifetime of H2 between 1.1-3.1 years. The atmospheric H2 is replenished by emissions from the Earth’s surfaces due to fossil fuel burning (5-25 Tg/yr), biomass burning (7-21 Tg/yr) and nitrogen fixation processes in the oceans (1-11 Tg/yr) and soils (0-11 Tg/yr). H2 is photochemically produced from methane (15-21 Tg/yr) and non-methane hydrocarbons (10-25 Tg/yr) in the atmosphere. These uncertainties suggest that at present, the global hydrogen cycle is poorly understood. However, this statement would do little justice to the scientific quality of most studies so far. The main purpose of the research in this thesis is to

  5. Molecular Modeling of Interfacial Behaviors of Nanomaterials

    DTIC Science & Technology

    2007-05-01

    principles quantum mechanical calculations predicting density of reactive surface sitesfor functionalization with benzene molecules, Surface...techniques, including first-principles quantum mechanical calculations and reactive molecular dynamics simulations. We successfully carried out proof-of...principles quantum mechanical calculations to gain a more accu- rate description of atomic interactions across interfaces, and by coarse-grained particle

  6. GPU-Accelerated Molecular Modeling Coming Of Age

    PubMed Central

    Stone, John E.; Hardy, David J.; Ufimtsev, Ivan S.

    2010-01-01

    Graphics processing units (GPUs) have traditionally been used in molecular modeling solely for visualization of molecular structures and animation of trajectories resulting from molecular dynamics simulations. Modern GPUs have evolved into fully programmable, massively parallel co-processors that can now be exploited to accelerate many scientific computations, typically providing about one order of magnitude speedup over CPU code and in special cases providing speedups of two orders of magnitude. This paper surveys the development of molecular modeling algorithms that leverage GPU computing, the advances already made and remaining issues to be resolved, and the continuing evolution of GPU technology that promises to become even more useful to molecular modeling. Hardware acceleration with commodity GPUs is expected to benefit the overall computational biology community by bringing teraflops performance to desktop workstations and in some cases potentially changing what were formerly batch-mode computational jobs into interactive tasks. PMID:20675161

  7. Investigating molecular structures: Rapidly examining molecular fingerprints through fast passage broadband fourier transform microwave spectroscopy

    NASA Astrophysics Data System (ADS)

    Grubbs, Garry Smith Smitty, II

    Microwave spectroscopy is a gas phase technique typically geared toward measuring the rotational transitions of molecules. The information contained in this type of spectroscopy pertains to a molecules structure, both geometric and electronic, which give insight into a molecule's chemistry. Typically this type of spectroscopy is high resolution, but narrowband ≤1 MHz in frequency. This is achieved by tuning a cavity, exciting a molecule with electromagnetic radiation in the microwave region, turning the electromagnetic radiation off, and measuring a signal from the molecular relaxation in the form of a free induction decay (FID). The FID is then Fourier transformed to give a frequency of the transition. "Fast passage" is defined as a sweeping of frequencies through a transition at a time much shorter (≤10 mus) than the molecular relaxation (≈100 mus). Recent advancements in technology have allowed for the creation of these fast frequency sweeps, known as "chirps", which allow for broadband capabilities. This work presents the design, construction, and implementation of one such novel, high-resolution microwave spectrometer with broadband capabilities. The manuscript also provides the theory, technique, and motivations behind building of such an instrument. In this manuscript it is demonstrated that, although a gas phase technique, solids, liquids, and transient species may be studied with the spectrometer with high sensitivity, making it a viable option for many molecules wanting to be rotationally studied. The spectrometer has a relative correct intensity feature that, when coupled with theory, may ease the difficulty in transition assignment and facilitate dynamic chemical studies of the experiment. Molecules studied on this spectrometer have, in turn, been analyzed and assigned using common rotational spectroscopic analysis. Detailed theory on the analysis of these molecules has been provided. Structural parameters such as rotational constants and

  8. Molecular mechanics modeling of azobenzene-based photoswitches.

    PubMed

    Duchstein, Patrick; Neiss, Christian; Görling, Andreas; Zahn, Dirk

    2012-06-01

    We present an extension of the generalized amber force field to allow the modeling of azobenzenes by means of classical molecular mechanics. TD-DFT calculations were employed to derive different interaction models for 4-hydroxy-4'-methyl-azobenzene, including the ground (S(0)) and S(1) excited state. For both states, partial charges and the -N = N- torsion potentials were characterized. On this basis, we pave the way to large-scale model simulations involving azobenzene molecular switches. Using the example of an isolated molecule, the mechanics of cyclic switching processes are demonstrated by classical molecular dynamics simulations.

  9. Investigating interventions in Alzheimer's disease with computer simulation models.

    PubMed

    Proctor, Carole J; Boche, Delphine; Gray, Douglas A; Nicoll, James A R

    2013-01-01

    Progress in the development of therapeutic interventions to treat or slow the progression of Alzheimer's disease has been hampered by lack of efficacy and unforeseen side effects in human clinical trials. This setback highlights the need for new approaches for pre-clinical testing of possible interventions. Systems modelling is becoming increasingly recognised as a valuable tool for investigating molecular and cellular mechanisms involved in ageing and age-related diseases. However, there is still a lack of awareness of modelling approaches in many areas of biomedical research. We previously developed a stochastic computer model to examine some of the key pathways involved in the aggregation of amyloid-beta (Aβ) and the micro-tubular binding protein tau. Here we show how we extended this model to include the main processes involved in passive and active immunisation against Aβ and then demonstrate the effects of this intervention on soluble Aβ, plaques, phosphorylated tau and tangles. The model predicts that immunisation leads to clearance of plaques but only results in small reductions in levels of soluble Aβ, phosphorylated tau and tangles. The behaviour of this model is supported by neuropathological observations in Alzheimer patients immunised against Aβ. Since, soluble Aβ, phosphorylated tau and tangles more closely correlate with cognitive decline than plaques, our model suggests that immunotherapy against Aβ may not be effective unless it is performed very early in the disease process or combined with other therapies.

  10. Modeling adsorption: Investigating adsorbate and adsorbent properties

    NASA Astrophysics Data System (ADS)

    Webster, Charles Edwin

    1999-12-01

    Surface catalyzed reactions play a major role in current chemical production technology. Currently, 90% of all chemicals are produced by heterogeneously catalyzed reactions. Most of these catalyzed reactions involve adsorption, concentrating the substrate(s) (the adsorbate) on the surface of the solid (the adsorbent). Pore volumes, accessible surface areas, and the thermodynamics of adsorption are essential in the understanding of solid surface characteristics fundamental to catalyst and adsorbent screening and selection. Molecular properties such as molecular volumes and projected molecular areas are needed in order to convert moles adsorbed to surface volumes and areas. Generally, these molecular properties have been estimated from bulk properties, but many assumptions are required. As a result, different literature values are employed for these essential molecular properties. Calculated molar volumes and excluded molecular areas are determined and tabulated for a variety of molecules. Molecular dimensions of molecules are important in the understanding of molecular exclusion as well as size and shape selectivity, diffusion, and adsorbent selection. Molecular dimensions can also be used in the determination of the effective catalytic pore size of a catalyst. Adsorption isotherms, on zeolites, (crystalline mineral oxides) and amorphous solids, can be analyzed with the Multiple Equilibrium Analysis (MEA) description of adsorption. The MEA produces equilibrium constants (Ki), capacities (ni), and thermodynamic parameters (enthalpies, ΔHi, and entropies, ΔSi) of adsorption for each process. Pore volumes and accessible surface areas are calculated from the process capacities. Adsorption isotherms can also be predicted for existing and new adsorbate-adsorbent systems with the MEA. The results show that MEA has the potential of becoming a standard characterization method for microporous solids that will lead to an increased understanding of their behavior in gas

  11. Molecular dynamics investigation of the interaction of dislocations with carbides in BCC Fe

    NASA Astrophysics Data System (ADS)

    Granberg, F.; Terentyev, D.; Nordlund, K.

    2015-06-01

    Different types of carbides are present in many steels used as structural materials. To safely use steel in demanding environments, like nuclear power plants, it is important to know how defects will affect the mechanical properties of the material. In this study, the effect of carbide precipitates on the edge dislocation movement is investigated. Three different types of carbides were investigated by means of molecular dynamics, with a Tersoff-like bond order interatomic potential by Henriksson et al. The obstacles were 4 nm in diameter and were of Fe3C- (cementite-), Fe23C6- and Cr23C6-type. The critical unpinning stress was calculated for each type at different temperatures, to get the temperature-dependent obstacle strength. The results showed a decreasing critical stress with increasing temperature, consistent with previous studies. The critical unpinning stress was seen to be dependent on the type of carbide, but the differences were small. A difference was also observed between the obstacles with the same structure, but with different composition. This study shows the relation between the existing Cr23C6 carbide and the experimentally non-existing Fe23C6 carbide, which needs to be used as a model system for investigations with interatomic potentials not able to describe the interaction of Cr in the Fe-C-system. We found the difference to be a between 7% and 10% higher critical unpinning stress for the chromium carbide, than for the iron carbide of the same type.

  12. A nanostructural investigation of glassy gelatin oligomers: molecular organization and interactions with low molecular weight diluents

    NASA Astrophysics Data System (ADS)

    Roussenova, M.; Enrione, J.; Diaz-Calderon, P.; Taylor, A. J.; Ubbink, J.; Alam, M. A.

    2012-03-01

    The effects of low molecular weight diluents (namely water and glycerol) on the nanostructure and thermodynamic state of low water content gelatin matrices are explored systematically by combining positron annihilation lifetime spectroscopy (PALS) with calorimetric measurements. Bovine gelatin matrices with a variation in the glycerol content (0-10 wt.%) are equilibrated in a range of water activities (aw = 0.11-0.68, T = 298 K). Both water and glycerol reduce the glass transition temperature, Tg, and the temperature of dissociation of the ordered triple helical segments, Tm, while having no significant effect on the level of re-naturation of the gelatin matrices. Our PALS measurements show that over the concentration range studied, glycerol acts as a packing enhancer and in the glassy state it causes a nonlinear decrease in the average hole size, vh, of the gelatin matrices. Finally, we report complex changes in vh for the gelatin matrices as a function of the increasing level of hydration. At low water contents (Qw ˜ 0.01-0.10), water acts as a plasticizer, causing a systematic increase in vh. Conversely, for water contents higher than Qw ˜ 0.10, vh is found to decrease, as small clusters of water begin to form between the polypeptide chains.

  13. Molecular Modeling and Computational Chemistry at Humboldt State University.

    ERIC Educational Resources Information Center

    Paselk, Richard A.; Zoellner, Robert W.

    2002-01-01

    Describes a molecular modeling and computational chemistry (MM&CC) facility for undergraduate instruction and research at Humboldt State University. This facility complex allows the introduction of MM&CC throughout the chemistry curriculum with tailored experiments in general, organic, and inorganic courses as well as a new molecular modeling…

  14. Nanoindentation of virus capsids in a molecular model

    NASA Astrophysics Data System (ADS)

    Cieplak, Marek; Robbins, Mark O.

    2010-01-01

    A molecular-level model is used to study the mechanical response of empty cowpea chlorotic mottle virus (CCMV) and cowpea mosaic virus (CPMV) capsids. The model is based on the native structure of the proteins that constitute the capsids and is described in terms of the Cα atoms. Nanoindentation by a large tip is modeled as compression between parallel plates. Plots of the compressive force versus plate separation for CCMV are qualitatively consistent with continuum models and experiments, showing an elastic region followed by an irreversible drop in force. The mechanical response of CPMV has not been studied, but the molecular model predicts an order of magnitude higher stiffness and a much shorter elastic region than for CCMV. These large changes result from small structural changes that increase the number of bonds by only 30% and would be difficult to capture in continuum models. Direct comparison of local deformations in continuum and molecular models of CCMV shows that the molecular model undergoes a gradual symmetry breaking rotation and accommodates more strain near the walls than the continuum model. The irreversible drop in force at small separations is associated with rupturing nearly all of the bonds between capsid proteins in the molecular model, while a buckling transition is observed in continuum models.

  15. Growth mechanism, electronic spectral investigation and molecular orbital studies of L-prolinium phosphate.

    PubMed

    Liu, Xiaojing; Sun, Xin; Xu, Xijin; Sun, Ping

    2015-01-01

    By using atomic force microscopy, birth and spread has proved to be the primary growth mechanism for L-prolinium phosphate (LPP). The phenomenon of newly formed islands expanding to the edge of the preceding terrace was observed. The optimized molecular structure and the molecular properties were calculated by density functional theory method. Natural bond orbital analysis was carried out to demonstrate the various inter and intramolecular interactions that are responsible for the stabilization of LPP leading to high NLO activity. Molecular electrostatic potential, frontier molecular orbital analysis and thermodynamic properties were investigated to get a better insight of the molecular properties. Global and local reactivity descriptors were computed to predict the reactivity and reactive sites on the molecules. Non-linear optical (NLO) properties such as the total dipole moment (μ) and first order hyperopolarizability (β) were also calculated to predict NLO behavior.

  16. Investigation of the resonance-assisted hydrogen bond in model β-diketones through localized molecular orbital analysis of the spin-spin coupling constants related to the O-H···O hydrogen bond.

    PubMed

    Zarycz, M Natalia C; Provasi, Patricio F

    2015-02-01

    The resonance-assisted hydrogen bond (HB) phenomenon has been studied theoretically by a localized molecular orbital (LMO) decomposition of the spin-spin coupling constants between atoms either involved or close to the O-H···O system of some β-diketones and their saturated counterparts. The analysis, carried out at the level of the second-order polarization propagator approximation, shows that the contributions in terms of LMO to the paramagnetic spin orbital and the spin dipolar Ramsey terms proof the importance of the delocalized π-electron structure supporting the idea of the existence of the resonance-assisted HB phenomenon phenomenon. The LMO contributions to the Fermi contact term indicate mainly the presence of the HB that may or not be linked to the π-electrons.

  17. A model for including thermal conduction in molecular dynamics simulations

    NASA Technical Reports Server (NTRS)

    Wu, Yue; Friauf, Robert J.

    1989-01-01

    A technique is introduced for including thermal conduction in molecular dynamics simulations for solids. A model is developed to allow energy flow between the computational cell and the bulk of the solid when periodic boundary conditions cannot be used. Thermal conduction is achieved by scaling the velocities of atoms in a transitional boundary layer. The scaling factor is obtained from the thermal diffusivity, and the results show good agreement with the solution for a continuous medium at long times. The effects of different temperature and size of the system, and of variations in strength parameter, atomic mass, and thermal diffusivity were investigated. In all cases, no significant change in simulation results has been found.

  18. Application of Molecular Modeling to Biological Processes

    DTIC Science & Technology

    1993-07-01

    informa- tion. DNA is the storehouse for the information that ultimately governs the synthesis of all biomolecules. It is generally found in the Watson ... Crick double helix . Breakthroughs in computer graphics and simulations have discovered that intercalation of flat aromatic rings is a major mechanism...for mutations.’ 0 Using molecular mechanics, docking studies show that molecules (e.g., acridine) can insert through the edge of the DNA helix . This

  19. Bayesian modelling of compositional heterogeneity in molecular phylogenetics.

    PubMed

    Heaps, Sarah E; Nye, Tom M W; Boys, Richard J; Williams, Tom A; Embley, T Martin

    2014-10-01

    In molecular phylogenetics, standard models of sequence evolution generally assume that sequence composition remains constant over evolutionary time. However, this assumption is violated in many datasets which show substantial heterogeneity in sequence composition across taxa. We propose a model which allows compositional heterogeneity across branches, and formulate the model in a Bayesian framework. Specifically, the root and each branch of the tree is associated with its own composition vector whilst a global matrix of exchangeability parameters applies everywhere on the tree. We encourage borrowing of strength between branches by developing two possible priors for the composition vectors: one in which information can be exchanged equally amongst all branches of the tree and another in which more information is exchanged between neighbouring branches than between distant branches. We also propose a Markov chain Monte Carlo (MCMC) algorithm for posterior inference which uses data augmentation of substitutional histories to yield a simple complete data likelihood function that factorises over branches and allows Gibbs updates for most parameters. Standard phylogenetic models are not informative about the root position. Therefore a significant advantage of the proposed model is that it allows inference about rooted trees. The position of the root is fundamental to the biological interpretation of trees, both for polarising trait evolution and for establishing the order of divergence among lineages. Furthermore, unlike some other related models from the literature, inference in the model we propose can be carried out through a simple MCMC scheme which does not require problematic dimension-changing moves. We investigate the performance of the model and priors in analyses of two alignments for which there is strong biological opinion about the tree topology and root position.

  20. Molecular and Cellular Quantitative Microscopy: theoretical investigations, technological developments and applications to neurobiology

    NASA Astrophysics Data System (ADS)

    Esposito, Alessandro

    2006-05-01

    This PhD project aims at the development and evaluation of microscopy techniques for the quantitative detection of molecular interactions and cellular features. The primarily investigated techniques are Fαrster Resonance Energy Transfer imaging and Fluorescence Lifetime Imaging Microscopy. These techniques have the capability to quantitatively probe the biochemical environment of fluorophores. An automated microscope capable of unsupervised operation has been developed that enables the investigation of molecular and cellular properties at high throughput levels and the analysis of cellular heterogeneity. State-of-the-art Förster Resonance Energy Transfer imaging, Fluorescence Lifetime Imaging Microscopy, Confocal Laser Scanning Microscopy and the newly developed tools have been combined with cellular and molecular biology techniques for the investigation of protein-protein interactions, oligomerization and post-translational modifications of α-Synuclein and Tau, two proteins involved in Parkinson’s and Alzheimer’s disease, respectively. The high inter-disciplinarity of this project required the merging of the expertise of both the Molecular Biophysics Group at the Debye Institute - Utrecht University and the Cell Biophysics Group at the European Neuroscience Institute - Gαttingen University. This project was conducted also with the support and the collaboration of the Center for the Molecular Physiology of the Brain (Göttingen), particularly with the groups associated with the Molecular Quantitative Microscopy and Parkinson’s Disease and Aggregopathies areas. This work demonstrates that molecular and cellular quantitative microscopy can be used in combination with high-throughput screening as a powerful tool for the investigation of the molecular mechanisms of complex biological phenomena like those occurring in neurodegenerative diseases.

  1. Investigation of the radiation-stimulated oxidation of sulfide by molecular oxygen

    SciTech Connect

    Muratbekov, M.B.; Beremzhanov, B.A.; Koroleva, G.Y.

    1986-07-01

    In order to determine the possibility of radiation stimulation of the oxidation of dissolved sulfide by molecular oxygen and to consider the mechanism from the standpoint of radiation chemical concepts, the authors investigated the radiation-stimulated oxidation of sulfide by molecular oxygen at pH 13. The kinetics were studied according to the decrease in oxygen with the aid of a gasometric set up.

  2. Theoretical Investigation Leading to Energy Storage in Atomic and Molecular Systems

    DTIC Science & Technology

    1990-12-01

    maintenance of equivalent quality of calculation for nuclear geometries differing in the nature or number of chemical bonds ; (iii) ability to describe...function. In order to calculate properties for such states, or to investigate the formation of molecular bonds , one often needs multiconfiguration wave...of calculating one-electron properties and analyzing molecular charge distributions, and various ’post-SCF’ stages, beginning with a 4- index

  3. An Investigation of Molecular Docking and Molecular Dynamic Simulation on Imidazopyridines as B-Raf Kinase Inhibitors.

    PubMed

    Xie, Huiding; Li, Yupeng; Yu, Fang; Xie, Xiaoguang; Qiu, Kaixiong; Fu, Jijun

    2015-11-16

    In the recent cancer treatment, B-Raf kinase is one of key targets. Nowadays, a group of imidazopyridines as B-Raf kinase inhibitors have been reported. In order to investigate the interaction between this group of inhibitors and B-Raf kinase, molecular docking, molecular dynamic (MD) simulation and binding free energy (ΔGbind) calculation were performed in this work. Molecular docking was carried out to identify the key residues in the binding site, and MD simulations were performed to determine the detail binding mode. The results obtained from MD simulation reveal that the binding site is stable during the MD simulations, and some hydrogen bonds (H-bonds) in MD simulations are different from H-bonds in the docking mode. Based on the obtained MD trajectories, ΔGbind was computed by using Molecular Mechanics Generalized Born Surface Area (MM-GBSA), and the obtained energies are consistent with the activities. An energetic analysis reveals that both electrostatic and van der Waals contributions are important to ΔGbind, and the unfavorable polar solvation contribution results in the instability of the inhibitor with the lowest activity. These results are expected to understand the binding between B-Raf and imidazopyridines and provide some useful information to design potential B-Raf inhibitors.

  4. An Investigation of Molecular Docking and Molecular Dynamic Simulation on Imidazopyridines as B-Raf Kinase Inhibitors

    PubMed Central

    Xie, Huiding; Li, Yupeng; Yu, Fang; Xie, Xiaoguang; Qiu, Kaixiong; Fu, Jijun

    2015-01-01

    In the recent cancer treatment, B-Raf kinase is one of key targets. Nowadays, a group of imidazopyridines as B-Raf kinase inhibitors have been reported. In order to investigate the interaction between this group of inhibitors and B-Raf kinase, molecular docking, molecular dynamic (MD) simulation and binding free energy (ΔGbind) calculation were performed in this work. Molecular docking was carried out to identify the key residues in the binding site, and MD simulations were performed to determine the detail binding mode. The results obtained from MD simulation reveal that the binding site is stable during the MD simulations, and some hydrogen bonds (H-bonds) in MD simulations are different from H-bonds in the docking mode. Based on the obtained MD trajectories, ΔGbind was computed by using Molecular Mechanics Generalized Born Surface Area (MM-GBSA), and the obtained energies are consistent with the activities. An energetic analysis reveals that both electrostatic and van der Waals contributions are important to ΔGbind, and the unfavorable polar solvation contribution results in the instability of the inhibitor with the lowest activity. These results are expected to understand the binding between B-Raf and imidazopyridines and provide some useful information to design potential B-Raf inhibitors. PMID:26580609

  5. An investigation of molecular dynamics simulation and molecular docking: interaction of citrus flavonoids and bovine β-lactoglobulin in focus.

    PubMed

    Sahihi, M; Ghayeb, Y

    2014-08-01

    Citrus flavonoids are natural compounds with important health benefits. The study of their interaction with a transport protein, such as bovine β-lactoglobulin (BLG), at the atomic level could be a valuable factor to control their transport to biological sites. In the present study, molecular docking and molecular dynamics simulation methods were used to investigate the interaction of hesperetin, naringenin, nobiletin and tangeretin as citrus flavonoids and BLG as transport protein. The molecular docking results revealed that these flavonoids bind in the internal cavity of BLG and the BLG affinity for binding the flavonoids follows naringenin>hesperetin>tangeretin>nobiletin. The docking results also indicated that the BLG-flavonoid complexes are stabilized through hydrophobic interactions, hydrogen bond interactions and π-π stacking interactions. The analysis of molecular dynamics (MD) simulation trajectories showed that the root mean square deviation (RMSD) of various systems reaches equilibrium and fluctuates around the mean value at various times. Time evolution of the radius of gyration, total solvent accessible surface of the protein and the second structure of protein showed as well that BLG and BLG-flavonoid complexes were stable around 2500ps, and there was not any conformational change as for BLG-flavonoid complexes. Further, the profiles of atomic fluctuations indicated the rigidity of the ligand binding site during the simulation.

  6. Constructing Molecular Models with Low-Cost Toy Beads

    ERIC Educational Resources Information Center

    Ng, Pun-hon; Wong, Siu-ling; Mak, Se-yuen

    2012-01-01

    In teaching the science of the nano world, ball-and-stick molecular models are frequently used as 3D representations of molecules. Unlike a chemical formula, a molecular model allows us to visualise the 3D shape of the molecule and the relative positions of its atoms, the bonds between atoms and why a pair of mirror isomers with the same atoms,…

  7. Molecular dynamics investigation of hexagonal boron nitride sputtering and sputtered particle characteristics

    NASA Astrophysics Data System (ADS)

    Smith, Brandon D.; Boyd, Iain D.

    2016-08-01

    The sputtering of hexagonal boron nitride (h-BN) by impacts of energetic xenon ions is investigated using a molecular dynamics (MD) model. The model is implemented within an open-source MD framework that utilizes graphics processing units to accelerate its calculations, allowing the sputtering process to be studied in much greater detail than has been feasible in the past. Integrated sputter yields are computed over a range of ion energies from 20 eV to 300 eV, and incidence angles from 0° to 75°. Sputtering of boron is shown to occur at energies as low as 40 eV at normal incidence, and sputtering of nitrogen at as low as 30 eV at normal incidence, suggesting a threshold energy between 20 eV and 40 eV. The sputter yields at 0° incidence are compared to existing experimental data and are shown to agree well over the range of ion energies investigated. The semi-empirical Bohdansky curve and an empirical exponential function are fit to the data at normal incidence, and the threshold energy for sputtering is calculated from the Bohdansky curve fit as 35 ± 2 eV. These results are shown to compare well with experimental observations that the threshold energy lies between 20 eV and 40 eV. It is demonstrated that h-BN sputters predominantly as atomic boron and diatomic nitrogen, and the velocity distribution function (VDF) of sputtered boron atoms is investigated. The calculated VDFs are found to reproduce the Sigmund-Thompson distribution predicted by Sigmund's linear cascade theory of sputtering. The average surface binding energy computed from Sigmund-Thompson curve fits is found to be 4.5 eV for ion energies of 100 eV and greater. This compares well to the value of 4.8 eV determined from independent experiments.

  8. Free volume model for molecular weights of polymers

    NASA Technical Reports Server (NTRS)

    Singh, J. J.; Eftekhari, A.

    1992-01-01

    A free volume model has been developed for determining molecular weights of linear polymers. It is based on the size of free volume cells in two geometries of poly(arylene ether ketone)s. Free volume cell sizes in test samples were measured using positron lifetime spectroscopy. The molecular weights computed from free volume cell sizes are in good agreement with the values measured by gel permeation chromatography, with a low angle laser light scattering photometer as the detector. The model has been further tested on two atactic polystyrene samples, where it predicted the ratio of their molecular weights with reasonable accuracy.

  9. Fracture of Carbon Nanotube - Amorphous Carbon Composites: Molecular Modeling

    NASA Technical Reports Server (NTRS)

    Jensen, Benjamin D.; Wise, Kristopher E.; Odegard, Gregory M.

    2015-01-01

    Carbon nanotubes (CNTs) are promising candidates for use as reinforcements in next generation structural composite materials because of their extremely high specific stiffness and strength. They cannot, however, be viewed as simple replacements for carbon fibers because there are key differences between these materials in areas such as handling, processing, and matrix design. It is impossible to know for certain that CNT composites will represent a significant advance over carbon fiber composites before these various factors have been optimized, which is an extremely costly and time intensive process. This work attempts to place an upper bound on CNT composite mechanical properties by performing molecular dynamics simulations on idealized model systems with a reactive forcefield that permits modeling of both elastic deformations and fracture. Amorphous carbon (AC) was chosen for the matrix material in this work because of its structural simplicity and physical compatibility with the CNT fillers. It is also much stiffer and stronger than typical engineering polymer matrices. Three different arrangements of CNTs in the simulation cell have been investigated: a single-wall nanotube (SWNT) array, a multi-wall nanotube (MWNT) array, and a SWNT bundle system. The SWNT and MWNT array systems are clearly idealizations, but the SWNT bundle system is a step closer to real systems in which individual tubes aggregate into large assemblies. The effect of chemical crosslinking on composite properties is modeled by adding bonds between the CNTs and AC. The balance between weakening the CNTs and improving fiber-matrix load transfer is explored by systematically varying the extent of crosslinking. It is, of course, impossible to capture the full range of deformation and fracture processes that occur in real materials with even the largest atomistic molecular dynamics simulations. With this limitation in mind, the simulation results reported here provide a plausible upper limit on

  10. Theoretical investigation of energy storage in atomic and molecular systems: Metastable molecular fuels

    NASA Astrophysics Data System (ADS)

    Saxon, Roberta P.

    1990-12-01

    Ion-pair species bound by the coulomb attraction between a stable positive and stable negative ion have been investigated theoretically as candidate high-energy fuels that could form the basis of new propulsion schemes. Theoretical results for H3O, Li3H, and H3F are presented along with specific impulse, I(sub sp), predictions based on calculated energies. The ion-pair local minimum on the first excited potential surface of H3O is found to be unstable with respect to dissociation to H2 + H + O. The ion-pair state of H3F has a double degenerate imaginary frequency. These results support the general conclusion that ion-pair states based on the H3 cation will not be stable because back-charge transfer to H3(+) leads to neutral H3, which is unstable with respect to H2 + H. However, the ion-pair state of Li3H is found to be a local minimum with a very small barrier to conversion to the lower energy planar form. Even the lowest energy form of Li3H as an additive to hydrogen is predicted to provide a 16 percent improvement in I(sub sp).

  11. Molecular modeling of responsive polymer films

    SciTech Connect

    Tagliazucchi, Mario; Calvo, Ernesto J; Szleifer, Igal

    2010-06-29

    In this perspective, we have shown three different cases of responsive polymers at surfaces where the properties of the surface can be varied in response to cues from the bulk solution or in the presence of an external field. The most important conclusion in all three cases is that the chemical reaction equilibrium, physical interactions and molecular organization are strongly coupled, and it is imperative to consider the global and local changes that occur to the surface structure and properties due to this coupling. In particular acid-base and redox equilibrium are very different in polymer-modified surfaces than in the corresponding bulk solutions. Moreover, the definition of ‘‘apparent redox potentials’’ and ‘‘apparent pKa’’results from the averaging over highly inhomogeneous values,and, therefore, they do not necessarily represent the state of the layer and the local values and their variation are very important for the design of functional surfaces. The very large variation on chemical equilibrium results from the optimization of all the interactions. The picture that emerges is that trying to deduce what the final state of the system is by looking at the individual optimization of each contribution leads to qualitative incorrect assumptions and only the minimization of the complete free energy leads to the proper behavior in these complex systems.In the cases where domain formation is possible in grafted weak polyacid layers charge regulation may lead to regimes of coexistence between aggregates with relatively low fraction of charged polymer segments surrounded by highly stretched chains that have a relatively high fraction of charged groups.Therefore, one can control the state of charge, local electrostatic potential and local pH in all three dimensions with im-portant gradients on length scales of nanometers. For hydrophobic redox polymers we show how the application of an electrode potential can lead to changes in the structure

  12. Experimental investigation of a flapping wing model

    NASA Astrophysics Data System (ADS)

    Hubel, Tatjana Y.; Tropea, Cameron

    2009-05-01

    The main objective of this research study was to investigate the aerodynamic forces of an avian flapping wing model system. The model size and the flow conditions were chosen to approximate the flight of a goose. Direct force measurements, using a three-component balance, and PIV flow field measurements parallel and perpendicular to the oncoming flow, were performed in a wind tunnel at Reynolds numbers between 28,000 and 141,000 (3-15 m/s), throughout a range of reduced frequencies between 0.04 and 0.20. The appropriateness of quasi-steady assumptions used to compare 2D, time-averaged particle image velocimetry (PIV) measurements in the wake with direct force measurements was evaluated. The vertical force coefficient for flapping wings was typically significantly higher than the maximum coefficient of the fixed wing, implying the influence of unsteady effects, such as delayed stall, even at low reduced frequencies. This puts the validity of the quasi-steady assumption into question. The (local) change in circulation over the wing beat cycle and the circulation distribution along the wingspan were obtained from the measurements in the tip and transverse vortex planes. Flow separation could be observed in the distribution of the circulation, and while the circulation derived from the wake measurements failed to agree exactly with the absolute value of the circulation, the change in circulation over the wing beat cycle was in excellent agreement for low and moderate reduced frequencies. The comparison between the PIV measurements in the two perpendicular planes and the direct force balance measurements, show that within certain limitations the wake visualization is a powerful tool to gain insight into force generation and the flow behavior on flapping wings over the wing beat cycle.

  13. Experimental investigation of a flapping wing model

    NASA Astrophysics Data System (ADS)

    Hubel, Tatjana Y.; Tropea, Cameron

    The main objective of this research study was to investigate the aerodynamic forces of an avian flapping wing model system. The model size and the flow conditions were chosen to approximate the flight of a goose. Direct force measurements, using a three-component balance, and PIV flow field measurements parallel and perpendicular to the oncoming flow, were performed in a wind tunnel at Reynolds numbers between 28,000 and 141,000 (3-15 m/s), throughout a range of reduced frequencies between 0.04 and 0.20. The appropriateness of quasi-steady assumptions used to compare 2D, time-averaged particle image velocimetry (PIV) measurements in the wake with direct force measurements was evaluated. The vertical force coefficient for flapping wings was typically significantly higher than the maximum coefficient of the fixed wing, implying the influence of unsteady effects, such as delayed stall, even at low reduced frequencies. This puts the validity of the quasi-steady assumption into question. The (local) change in circulation over the wing beat cycle and the circulation distribution along the wingspan were obtained from the measurements in the tip and transverse vortex planes. Flow separation could be observed in the distribution of the circulation, and while the circulation derived from the wake measurements failed to agree exactly with the absolute value of the circulation, the change in circulation over the wing beat cycle was in excellent agreement for low and moderate reduced frequencies. The comparison between the PIV measurements in the two perpendicular planes and the direct force balance measurements, show that within certain limitations the wake visualization is a powerful tool to gain insight into force generation and the flow behavior on flapping wings over the wing beat cycle.

  14. Molecular dynamics simulations of water within models of ion channels.

    PubMed

    Breed, J; Sankararamakrishnan, R; Kerr, I D; Sansom, M S

    1996-04-01

    The transbilayer pores formed by ion channel proteins contain extended columns of water molecules. The dynamic properties of such waters have been suggested to differ from those of water in its bulk state. Molecular dynamics simulations of ion channel models solvated within and at the mouths of their pores are used to investigate the dynamics and structure of intra-pore water. Three classes of channel model are investigated: a) parallel bundles of hydrophobic (Ala20) alpha-helices; b) eight-stranded hydrophobic (Ala10) antiparallel beta-barrels; and c) parallel bundles of amphipathic alpha-helices (namely, delta-toxin, alamethicin, and nicotinic acetylcholine receptor M2 helix). The self-diffusion coefficients of water molecules within the pores are reduced significantly relative to bulk water in all of the models. Water rotational reorientation rates are also reduced within the pores, particularly in those pores formed by alpha-helix bundles. In the narrowest pore (that of the Ala20 pentameric helix bundle) self-diffusion coefficients and reorientation rates of intra-pore waters are reduced by approximately an order of magnitude relative to bulk solvent. In Ala20 helix bundles the water dipoles orient antiparallel to the helix dipoles. Such dipole/dipole interaction between water and pore may explain how water-filled ion channels may be formed by hydrophobic helices. In the bundles of amphipathic helices the orientation of water dipoles is modulated by the presence of charged side chains. No preferential orientation of water dipoles relative to the pore axis is observed in the hydrophobic beta-barrel models.

  15. Investigating biological systems using first principles Car-Parrinello molecular dynamics simulations.

    PubMed

    Dal Peraro, Matteo; Ruggerone, Paolo; Raugei, Simone; Gervasio, Francesco Luigi; Carloni, Paolo

    2007-04-01

    Density functional theory (DFT)-based Car-Parrinello molecular dynamics (CPMD) simulations describe the time evolution of molecular systems without resorting to a predefined potential energy surface. CPMD and hybrid molecular mechanics/CPMD schemes have recently enabled the calculation of redox properties of electron transfer proteins in their complex biological environment. They provided structural and spectroscopic information on novel platinum-based anticancer drugs that target DNA, also setting the basis for the construction of force fields for the metal lesion. Molecular mechanics/CPMD also lead to mechanistic hypotheses for a variety of metalloenzymes. Recent advances that increase the accuracy of DFT and the efficiency of investigating rare events are further expanding the domain of CPMD applications to biomolecules.

  16. Comparative molecular modelling of biologically active sterols

    NASA Astrophysics Data System (ADS)

    Baran, Mariusz; Mazerski, Jan

    2015-04-01

    Membrane sterols are targets for a clinically important antifungal agent - amphotericin B. The relatively specific antifungal action of the drug is based on a stronger interaction of amphotericin B with fungal ergosterol than with mammalian cholesterol. Conformational space occupied by six sterols has been defined using the molecular dynamics method to establish if the conformational features correspond to the preferential interaction of amphotericin B with ergosterol as compared with cholesterol. The compounds studied were chosen on the basis of structural features characteristic for cholesterol and ergosterol and on available experimental data on the ability to form complexes with the antibiotic. Statistical analysis of the data obtained has been performed. The results show similarity of the conformational spaces occupied by all the sterols tested. This suggests that the conformational differences of sterol molecules are not the major feature responsible for the differential sterol - drug affinity.

  17. Testing Equilibrium Models of Molecular Gas in the Magellanic Clouds

    NASA Astrophysics Data System (ADS)

    Wong, Tony

    We propose to study the molecular gas fractions and physical conditions of diffuse molecular clouds in the Magellanic Clouds using ultraviolet (UV) and optical absorption spectra, principally from the Far Ultraviolet Spectroscopic Explorer (FUSE) and Hubble Space Telescope (HST) archives. We will use these data to constrain the abundance of molecular hydrogen (H_2) undetectable in CO emission surveys and to test equilibrium models that seek to predict the H_2 mass fraction and the H_2/HI ratio as functions of metallicity, column density, and thermal pressure. Our approach complements HI and CO surveys by providing direct estimates of HI and H_2 column densities. For sight lines where sufficiently high resolution spectra are available, we will use the excitation of CI to determine thermal pressures, allowing us to test models that assume thermodynamic equilibrium in order to determine the HI-H_2 balance. The recently completed Spitzer Legacy surveys of the MCs provide images of PAH emission on sub-parsec scales, which may provide a means to model the distribution and small-scale clumping of gas in the vicinity of the absorption sight lines, and thus connect the absorption data with the much coarser resolution radio data. We will investigate this possibility and the implications that small-scale clumping have for comparisons with theoretical models. A preliminary analysis of the FUSE and HST data is already underway, and we present a few early results. We seek support to continue this effort over the next two years and to disseminate our results. Our methodology is novel in several respects. It includes the use of high-resolution optical spectra to derive component models for the FUSE absorption spectra, in order to derive more accurate column densities, especially for the higher J transitions of H_2 which provide key diagnostics of density and radiation field strength. Such component models will also aid in the analysis of the CI spectra. We will work to increase

  18. A Student Evaluation of Molecular Modeling in First Year College Chemistry.

    ERIC Educational Resources Information Center

    Ealy, Julie B.

    1999-01-01

    Evaluates first-year college students' perceptions of molecular modeling. Examines the effectiveness, integration with course content, interests, benefits, advantages, and disadvantages of molecular modeling. (Author/CCM)

  19. Investigation of the silicon ion density during molecular beam epitaxy growth

    NASA Astrophysics Data System (ADS)

    Eifler, G.; Kasper, E.; Ashurov, Kh.; Morozov, S.

    2002-05-01

    Ions impinging on a surface during molecular beam epitaxy influence the growth and the properties of the growing layer, for example, suppression of dopant segregation and the generation of crystal defects. The silicon electron gun in the molecular beam epitaxy (MBE) equipment is used as a source for silicon ions. To use the effect of ion bombardment the mechanism of generation and distribution of ions was investigated. A monitoring system was developed and attached at the substrate position in the MBE growth chamber to measure the ion and electron densities towards the substrate. A negative voltage was applied to the substrate to modify the ion energy and density. Furthermore the current caused by charge carriers impinging on the substrate was measured and compared with the results of the monitoring system. The electron and ion densities were measured by varying the emission current of the e-gun achieving silicon growth rates between 0.07 and 0.45 nm/s and by changing the voltage applied to the substrate between 0 to -1000 V. The dependencies of ion and electron densities were shown and discussed within the framework of a simple model. The charged carrier densities measured with the monitoring system enable to separate the ion part of the substrate current and show its correlation to the generation rate. Comparing the ion density on the whole substrate and in the center gives a hint to the ion beam focusing effect. The maximum ion and electron current densities obtained were 0.40 and 0.61 μA/cm2, respectively.

  20. Molecular Recognition in a Lattice Model: An Enumeration Study

    NASA Astrophysics Data System (ADS)

    Bogner, Thorsten; Degenhard, Andreas; Schmid, Friederike

    2004-12-01

    We investigate the mechanisms underlying selective molecular recognition of single heteropolymers at chemically structured planar surfaces. To this end, we study systems with two-letter (HP) lattice heteropolymers by exact enumeration techniques. Selectivity for a particular surface is defined by an adsorption energy criterion. We analyze the distributions of selective sequences and the role of mutations. A particularly important factor for molecular recognition is the small-scale structure on the polymers.

  1. Molecular Modeling on the PC (by Matthew F. Schlecht)

    NASA Astrophysics Data System (ADS)

    Rioux, Reviewed Frank

    2000-06-01

    "Computeraided molecular modeling doesn't exist for its own sake, but to contribute to scientific endeavor, and enable the scientist to work smarter." This is the last sentence of Schlecht's preface and it says something very important about contemporary scientific research in the academic and industrial venues. Owing to the accelerating improvement in computer technology (hardware and software) and its widespread availability, molecular modeling has become a reliable and important tool in chemical research. Consequently, experimentalists have incorporated molecular modeling techniques in their research, and partnerships with computational chemists have become common. This is a wellorganized and thorough monograph that devotes its attention to one type of molecular modeling, molecular mechanics, and one molecular modeling software package, PCMODEL. Schlecht targets two reader-user groups, the novice and the journeyman modeler, and articulates three goals. He wants to provide the novice with an introduction to molecular mechanics, and after that with some practical examples of the use of empirical force field calculations. His third goal is to provide the journeyman modeler with a reference work that will aid "further study and practice". These are potentially conflicting goals, but Schlecht is, in my opinion, successful because of the way his book is organized. A comprehensive treatment such as this one is not meant to be read from cover to cover, because it is both an exposition of basic principles and a user's manual. Therefore, the novice and the experienced modeler will undoubtedly use this book in different ways. For example, a novice modeler might be advised to read the Preface and Chapter 1, which together provide a broad introduction to the historical development and goals of molecular mechanics. From there the novice could go to Chapter 5 and read section 5.1 on the components of the molecular mechanics force field, which is presented in 22 pages with

  2. A molecular diffusion based utility model for Drosophila larval phototaxis

    PubMed Central

    2012-01-01

    Background Generally, utility based decision making models focus on experimental outcomes. In this paper we propose a utility model based on molecular diffusion to simulate the choice behavior of Drosophila larvae exposed to different light conditions. Methods In this paper, light/dark choice-based Drosophila larval phototaxis is analyzed with our molecular diffusion based model. An ISCEM algorithm is developed to estimate the model parameters. Results By applying this behavioral utility model to light intensity and phototaxis data, we show that this model fits the experimental data very well. Conclusions Our model provides new insights into decision making mechanisms in general. From an engineering viewpoint, we propose that the model could be applied to a wider range of decision making practices. PMID:22300450

  3. Investigation on the binding interaction between silybin and pepsin by spectral and molecular docking.

    PubMed

    Zeng, Hua-jin; You, Jing; Liang, Hui-li; Qi, Tingting; Yang, Ran; Qu, Ling-bo

    2014-06-01

    In this study, the binding mode of silybin with pepsin was investigated by spectroscopic and molecular docking methods. Silybin can interact with pepsin to form a silybin-pepsin complex. The binding constant, number of binding sites and thermodynamic parameters were measured, which indicated that silybin could spontaneously bind with pepsin mainly through hydrophobic interaction with one binding site. Molecular docking results revealed that silybin bound into the pepsin cavity site. Synchronous fluorescence and three-dimensional fluorescence results provide data concerning conformational and some micro-environmental changes of pepsin. Furthermore, in order to reveal whether the binding process can inhibit the activity of pepsin in vivo, the effect of silybin on pepsin activity in rat was investigated. The present study provides direct evidence at a molecular level to show that exposure to silybin could induce changes in the enzyme pepsin structure and function.

  4. Investigating System Dependability Modeling Using AADL

    NASA Technical Reports Server (NTRS)

    Hall, Brendan; Driscoll, Kevin R.; Madl, Gabor

    2013-01-01

    This report describes Architecture Analysis & Design Language (AADL) models for a diverse set of fault-tolerant, embedded data networks and describes the methods and tools used to created these models. It also includes error models per the AADL Error Annex. Some networks were modeled using Error Detection Isolation Containment Types (EDICT). This report gives a brief description for each of the networks, a description of its modeling, the model itself, and evaluations of the tools used for creating the models. The methodology includes a naming convention that supports a systematic way to enumerate all of the potential failure modes.

  5. Molecular modeling of amorphous, non-woven polymer networks.

    PubMed

    Krausse, Constantin A; Milek, Theodor; Zahn, Dirk

    2015-10-01

    We outline a simple and efficient approach to generating molecular models of amorphous polymer networks. Similar to established techniques of preparing woven polymer networks from quenching high-temperature molecular simulation runs, we use a molecular dynamics simulations of a generic melt as starting points. This generic melt is however only used to describe parts of the polymers, namely the cross-linker units which positions are adopted from particle positions of the quenched melt. Specific degrees of network connectivity are tuned by geometric criteria for linker-linker connections and by suitable multi-body interaction potentials applied to the generic melt simulations. Using this technique we demonstrate adjusting fourfold linker coordination in amorphous polymer networks comprising 10-20% under-coordinated linkers. Graphical Abstract Molecular modeling of amorphous, non-woven polymer networks.

  6. Solid-State Spectroscopic Investigation of Molecular Interactions between Clofazimine and Hypromellose Phthalate in Amorphous Solid Dispersions.

    PubMed

    Nie, Haichen; Su, Yongchao; Zhang, Mingtao; Song, Yang; Leone, Anthony; Taylor, Lynne S; Marsac, Patrick J; Li, Tonglei; Byrn, Stephen R

    2016-11-07

    It has been technically challenging to specify the detailed molecular interactions and binding motif between drugs and polymeric inhibitors in the solid state. To further investigate drug-polymer interactions from a molecular perspective, a solid dispersion of clofazimine (CLF) and hypromellose phthalate (HPMCP), with reported superior amorphous drug loading capacity and physical stability, was selected as a model system. The CLF-HPMCP interactions in solid dispersions were investigated by various solid state spectroscopic methods including ultraviolet-visible (UV-vis), infrared (IR), and solid-state NMR (ssNMR) spectroscopy. Significant spectral changes suggest that protonated CLF is ionically bonded to the carboxylate from the phthalyl substituents of HPMCP. In addition, multivariate analysis of spectra was applied to optimize the concentration of polymeric inhibitor used to formulate the amorphous solid dispersions. Most interestingly, proton transfer between CLF and carboxylic acid was experimentally investigated from 2D (1)H-(1)H homonuclear double quantum NMR spectra by utilizing the ultrafast magic-angle spinning (MAS) technique. The molecular interaction pattern and the critical bonding structure in CLF-HPMCP dispersions were further delineated by successfully correlating ssNMR findings with quantum chemistry calculations. These high-resolution investigations provide critical structural information on active pharmaceutical ingredient-polymer interaction, which can be useful for rational selection of appropriate polymeric carriers, which are effective crystallization inhibitors for amorphous drugs.

  7. Molecular Interaction between Magainin 2 and Model Membranes in Situ

    PubMed Central

    Nguyen, Khoi; Le Clair, Stéphanie V.; Ye, Shuji; Chen, Zhan

    2009-01-01

    In this paper, we investigated the molecular interactions of Magainin 2 with model cell membranes using Sum Frequency Generation (SFG) vibrational spectroscopy and Attenuated Total Reflectance – Fourier Transform Infrared spectroscopy (ATR-FTIR). Symmetric 1-Palmitoyl-2-Oleoyl-sn-Glycero-3-[Phospho-rac-(1-glycerol)] (POPG) and 1-Palmitoyl-2-Oleoyl-sn-Glycero-3-Phosphocholine (POPC) bilayers, which model the bacterial and mammalian cell membranes respectively, were used in the studies. It was observed by SFG that Magainin 2 orients relatively parallel to the POPG lipid bilayer surface at low solution concentrations, around 200 nM. When increasing the Magainin 2 concentration to 800 nM, both SFG and ATR-FTIR results indicate that Magainin 2 molecules insert into the POPG bilayer and adopt a transmembrane orientation with an angle of about 20 degrees from the POPG bilayer normal. For the POPC bilayer, even at a much higher peptide concentration of 2.0 µM, no ATR-FTIR signal was detected. For this concentration on POPC, SFG studies indicated that Magainin 2 molecules adopt an orientation nearly parallel to the bilayer surface, with an orientation angle of 75 degrees from the surface normal. This shows that SFG has a much better detection limit than ATR-FTIR and can therefore be applied to study interfacial molecules with much lower surface coverage. This Magainin 2 orientation study and further investigation of the lipid bilayer SFG signals support the proposed toroidal pore model for the antimicrobial activity of Magainin 2. PMID:19728722

  8. Reasoning with Atomic-Scale Molecular Dynamic Models

    ERIC Educational Resources Information Center

    Pallant, Amy; Tinker, Robert F.

    2004-01-01

    The studies reported in this paper are an initial effort to explore the applicability of computational models in introductory science learning. Two instructional interventions are described that use a molecular dynamics model embedded in a set of online learning activities with middle and high school students in 10 classrooms. The studies indicate…

  9. The Electron-Pair Repulsion Model for Molecular Geometry

    ERIC Educational Resources Information Center

    Gillespie, R. J.

    1970-01-01

    Describes how the electron-pair repulsion model qualitatively explains the size and shape of molecular orbitals. Briefly discusses trigonal bipyramidal molecules, three-center bonds, and transition elements. Describes cluster compounds and finishes with a discussion of the exceptions to the model and effects of ligand-ligand repulsions. (RR)

  10. Molecular Models for DNA Damaged by Photoreaction

    NASA Astrophysics Data System (ADS)

    Pearlman, David A.; Holbrook, Stephen R.; Pirkle, David H.; Kim, Sung-Hou

    1985-03-01

    Structural models of a DNA molecule containing a radiation-induced psoralen cross-link and of a DNA containing a thymine photodimer were constructed by applying energy-minimization techniques and model-building procedures to data from x-ray crystallographic studies. The helical axes of the models show substantial kinking and unwinding at the sites of the damage, which may have long-range as well as local effects arising from the concomitant changes in the supercoiling and overall structure of the DNA. The damaged areas may also serve as recognition sites for repair enzymes. These results should help in understanding the biologic effects of radiation-induced damage on cells.

  11. Molecular models for DNA damaged by photoreaction

    SciTech Connect

    Pearlman, D.A.; Holbrook, S.R.; Pirkle, D.H.; Kim, S.H.

    1985-03-15

    Structural models of a DNA molecule containing a radiation-induced psoralen cross-link and of a DNA containing a thymine photodimer were constructed by applying energy-minimization techniques and model-building procedures to data from x-ray crystallographic studies. The helical axes of the models show substantial kinking and unwinding at the sites of the damage, which may have long-range as well as local effects arising from the concomitant changes in the supercoiling and overall structure of the DNA. The damaged areas may also serve as recognition sites for repair enzymes. These results should help in understanding the biologic effects of radiation-induced damage on cells.

  12. Relating Macroscopic Thermal Phenomena with Molecular Models

    NASA Astrophysics Data System (ADS)

    Laws, Priscilla W.

    2002-03-01

    A series of observations and activities have been developed to help students enrich their understanding of how physicists can use model building to construct self-consistent models of physical reality.* This talk will describe the instructional use of integrated microcomputer-based laboratory measurements of macroscopic phenomena and digital video analysis of simulated microscopic events to help students understand the ideal gas law, the first law of thermodynamics, and heat engines. *Workshop Physics Activity Guide (Module 3), P. Laws, (John Wiley and Sons, Inc., NY, 1997).

  13. Experimental and molecular mechanics and ab initio investigation of activated adsorption and desorption of trichloroethylene in mineral micropores.

    PubMed

    Farrell, James; Luo, Jing; Blowers, Paul; Curry, Joan

    2002-04-01

    This research investigated activated adsorption of a hydrophobic organic contaminant(HOC) in mineral micropores using experimental and molecular modeling techniques. Adsorption of trichloroethylene (TCE) on a silica gel adsorbent was measured using a frontal analysis chromatography technique at atmospheric and elevated fluid pressures. Increasing the fluid pressure yielded increased TCE uptake that was not released upon lowering the pressure back to atmospheric conditions. This showed that the increase in pressure was able to rapidly induce the formation of a desorption-resistant fraction that previous investigations have shown requires months to develop at atmospheric pressure. Grand Canonical Monte Carlo (GCMC) modeling was then used to elucidate the nature of water and TCE behavior within silica micropores. The GCMC modeling showed that molecular scale packing restrictions resulted in pore fluid densities that ranged from 0.28 to 0.78 of those in the bulk solution. The modeling also showed that TCE was able to displace water from hydrophilic mineral pores due to molecular scale packing restrictions. Exothermic isosteric heats for TCE adsorption up to -27 kJ/mol were observed and were greatest in pores of 7 and 8 A. This indicated that TCE adsorption was energetically most favorable in pores that were minimally large enough to accommodate a TCE molecule. The pressure-induced uptake appeared to result primarily from an increase in the packing density in the smallest pores. Ab initio calculations showed that small distortions of a TCE molecule from its low energy conformation require high activation energies. Results from this study indicate that activated adsorption requiring bond angle distortions in the adsorbate may be responsible forthe slow attainment of adsorptive equilibrium of HOCs on microporous solids. Likewise, activated desorption from molecular-sized adsorption sites may contribute to the slow release of HOCs from aquifer sediments.

  14. Molecular modeling: An open invitation for applied mathematics

    NASA Astrophysics Data System (ADS)

    Mezey, Paul G.

    2013-10-01

    Molecular modeling methods provide a very wide range of challenges for innovative mathematical and computational techniques, where often high dimensionality, large sets of data, and complicated interrelations imply a multitude of iterative approximations. The physical and chemical basis of these methodologies involves quantum mechanics with several non-intuitive aspects, where classical interpretation and classical analogies are often misleading or outright wrong. Hence, instead of the everyday, common sense approaches which work so well in engineering, in molecular modeling one often needs to rely on rather abstract mathematical constraints and conditions, again emphasizing the high level of reliance on applied mathematics. Yet, the interdisciplinary aspects of the field of molecular modeling also generates some inertia and perhaps too conservative reliance on tried and tested methodologies, that is at least partially caused by the less than up-to-date involvement in the newest developments in applied mathematics. It is expected that as more applied mathematicians take up the challenge of employing the latest advances of their field in molecular modeling, important breakthroughs may follow. In this presentation some of the current challenges of molecular modeling are discussed.

  15. Application of molecular modeling to polymer grafted nanostructures

    NASA Astrophysics Data System (ADS)

    Adiga, Shashishekar P.

    Polymer chains undergo conformational transitions in response to a change in solvent quality of their environment, making them strong candidates to be used in smart nanometer-scale devices. In the present work molecular modeling is used to explore grafted polymer structures with various functionalities. The first part of this research focuses on two examples of selective transport through nanopores modified with polymer brush structures. The first is the investigation of solvent flow through nanopores grafted with linear chains. Molecular dynamics (MD) simulations are used to demonstrate how a stretch-collapse transition in grafted polymer chains can be used to control solvent flow rate through a nanopore in response to environmental stimuli. A continuum fluid dynamics method based on porous layer model for describing flow through the smart nanopore is described and its accuracy is analyzed by comparing with the results from MD simulations. The continuum method is then applied to determine regulation of water permeation in response to pH through a poly(L-glutamic acid) grafted nanoporous membrane. A second example is use of a rod-coil transition in "bottle brush" molecules that are grafted to the inside of a nanopore to size select macromolecules as they diffuse through the functionalized nanopores. These stimuli-responsive nanopores have a variety of potential applications including molecular sorting, smart drug delivery, and ultrafiltration, as well as controlled chemical release. Tethered polymers play an important role in biological structures as well. In the second part of the research, application of atomistic simulations to characterize the effect of phosphorylation on neurofilament structure is presented. Neurofilaments are intermediate filaments that regulate axonal diameter through their long, flexible side arms extending from the central core. Their functionality is imparted by polymer brush like structure that causes steric repulsion between the

  16. Extracting Structure Parameters of Dimers for Molecular Tunneling Ionization Model

    NASA Astrophysics Data System (ADS)

    Song-Feng, Zhao; Fang, Huang; Guo-Li, Wang; Xiao-Xin, Zhou

    2016-03-01

    We determine structure parameters of the highest occupied molecular orbital (HOMO) of 27 dimers for the molecular tunneling ionization (so called MO-ADK) model of Tong et al. [Phys. Rev. A 66 (2002) 033402]. The molecular wave functions with correct asymptotic behavior are obtained by solving the time-independent Schrödinger equation with B-spline functions and molecular potentials which are numerically created using the density functional theory. We examine the alignment-dependent tunneling ionization probabilities from MO-ADK model for several molecules by comparing with the molecular strong-field approximation (MO-SFA) calculations. We show the molecular Perelomov-Popov-Terent'ev (MO-PPT) can successfully give the laser wavelength dependence of ionization rates (or probabilities). Based on the MO-PPT model, two diatomic molecules having valence orbital with antibonding systems (i.e., Cl2, Ne2) show strong ionization suppression when compared with their corresponding closest companion atoms. Supported by National Natural Science Foundation of China under Grant Nos. 11164025, 11264036, 11465016, 11364038, the Specialized Research Fund for the Doctoral Program of Higher Education of China under Grant No. 20116203120001, and the Basic Scientific Research Foundation for Institution of Higher Learning of Gansu Province

  17. Molecular road ecology: exploring the potential of genetics for investigating transportation impacts on wildlife.

    PubMed

    Balkenhol, Niko; Waits, Lisette P

    2009-10-01

    Transportation infrastructures such as roads, railroads and canals can have major environmental impacts. Ecological road effects include the destruction and fragmentation of habitat, the interruption of ecological processes and increased erosion and pollution. Growing concern about these ecological road effects has led to the emergence of a new scientific discipline called road ecology. The goal of road ecology is to provide planners with scientific advice on how to avoid, minimize or mitigate negative environmental impacts of transportation. In this review, we explore the potential of molecular genetics to contribute to road ecology. First, we summarize general findings from road ecology and review studies that investigate road effects using genetic data. These studies generally focus only on barrier effects of roads on local genetic diversity and structure and only use a fraction of available molecular approaches. Thus, we propose additional molecular applications that can be used to evaluate road effects across multiple scales and dimensions of the biodiversity hierarchy. Finally, we make recommendations for future research questions and study designs that would advance molecular road ecology. Our review demonstrates that molecular approaches can substantially contribute to road ecology research and that interdisciplinary, long-term collaborations will be particularly important for realizing the full potential of molecular road ecology.

  18. Corn Storage Protein - A Molecular Genetic Model

    SciTech Connect

    Messing, Joachim

    2013-05-31

    Corn is the highest yielding crop on earth and probably the most valuable agricultural product of the United States. Because it converts sun energy through photosynthesis into starch and proteins, we addressed energy savings by focusing on protein quality. People and animals require essential amino acids derived from the digestion of proteins. If proteins are relatively low in certain essential amino acids, the crop becomes nutritionally defective and has to be supplemented. Such deficiency affects meat and fish production and countries where corn is a staple. Because corn seed proteins have relatively low levels of lysine and methionine, a diet has to be supplemented with soybeans for the missing lysine and with chemically synthesized methionine. We therefore have studied genes expressed during maize seed development and their chromosomal organization. A critical technical requirement for the understanding of the molecular structure of genes and their positional information was DNA sequencing. Because of the length of sequences, DNA sequencing methods themselves were insufficient for this type of analysis. We therefore developed the so-called “DNA shotgun sequencing” strategy, where overlapping DNA fragments were sequenced in parallel and used to reconstruct large DNA molecules via overlaps. Our publications became the most frequently cited ones during the decade of 1981-1990 and former Associate Director of Science for the Office of Basic Energy Sciences Patricia M. Dehmer presented our work as one of the great successes of this program. A major component of the sequencing strategy was the development of bacterial strains and vectors, which were also used to develop the first biotechnology crops. These crops possessed new traits thanks to the expression of foreign genes in plants. To enable such expression, chimeric genes had to be constructed using our materials and methods by the industry. Because we made our materials and methods freely available to

  19. Homogeneous nucleation and growth in supersaturated zinc vapor investigated by molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Römer, F.; Kraska, T.

    2007-12-01

    Homogeneous nucleation and growth of zinc from supersaturated vapor are investigated by nonequilibrium molecular dynamics simulations in the temperature range from 400to800K and for a supersaturation ranging from logS =2 to 11. Argon is added to the vapor phase as carrier gas to remove the latent heat from the forming zinc clusters. A new parametrization of the embedded atom method for zinc is employed for the interaction potential model. The simulation data are analyzed with respect to the nucleation rates and the critical cluster sizes by two different methods, namely, the threshold method of Yasuoka and Matsumoto [J. Chem. Phys. 109, 8451 (1998)] and the mean first passage time method for nucleation by Wedekind et al. [J. Chem. Phys. 126, 134103 (2007)]. The nucleation rates obtained by these methods differ approximately by one order of magnitude. Classical nucleation theory fails to describe the simulation data as well as the experimental data. The size of the critical cluster obtained by the mean first passage time method is significantly larger than that obtained from the nucleation theorem.

  20. Investigation of imprinting parameters and their recognition nature for quinine-molecularly imprinted polymers

    NASA Astrophysics Data System (ADS)

    He, Jian-feng; Zhu, Quan-hong; Deng, Qin-ying

    2007-08-01

    A series of molecularly imprinted polymers (MIPs) was prepared using quinine as the template molecules by bulk polymerization. The presence of monomer-template solution complexes in non-covalent MIPs systems has been verified by both fluorescence and UV-vis spectrometric detection. The influence of different synthetic conditions (porogen, functional monomer, cross-linkers, initiation methods, monomer-template ratio, etc.) on recognition properties of the polymers was investigated. Scatchard analysis revealed that two classes of binding sites were formed in the imprinted polymer. The corresponding dissociation constants were estimated to be 45.00 μmol l -1 and 1.42 mmol l -1, respectively, by utilizing a multi-site recognition model. The binding characteristics of the imprinted polymers were explored in various solvents using equilibrium binding experiments. In the organic media, results suggested that polar interactions (hydrogen bonding, ionic interactions, etc.) between acidic monomer/polymer and template molecules were mainly responsible for the recognition, whereas in aqueous media, hydrophobic interactions had a remarkable non-specific contribution to the overall binding. The specificity of MIP was evaluated by rebinding the other structurally similar compounds. The results indicated that the imprinted polymers exhibited an excellent stereo-selectivity toward quinine.

  1. Methodology Investigation of Software Maturity Model Validation

    DTIC Science & Technology

    1989-11-13

    Cassondra Renfro provided helpful coments in the review of the report. I SEcTON 1. SUMALR 1.1 BACIRUND. Software h~s become a major part of Comuand...example, is that each software fault that is discovered is either corrected or not counted again. Brooks and Motley’s Models, on the other hand, assume...Between Error Occurrence ERROR COUNT MODELS 1 The Generalized Poisson Model 2 The Non - Homogeneous Poisson Model 3 The Brooks and Motley Model 4 The

  2. Investigating the productivity model for clinical nurses.

    PubMed

    Dehghan Nayeri, Nahid; Hooshmand Bahabadi, Abbas; Kazemnejad, Anoshirvan

    2014-01-01

    One of the main objectives of quantitative researches is assessment of models developed by qualitative studies. Models validation through their testing implies that the designed model is representative of the existed facts. Hence, this study was conducted to assess the clinical nurses' productivity model presented for Iranian nurses' productivity. The sample of the study consisted of 360 nurses of Tehran University of Medical Sciences. The research tool was a questionnaire for measuring the components of clinical nurses' productivity. After completing all steps of instrument psychometric and getting answers from the participants, the factors introduced in the questionnaire were named and then Lisrel Path Analysis tests were performed to analyze the components of the model. The results of the model test revealed there is an internal relationship among different components of the model. Regression Analysis showed that each increasing unit in components of the model was to be added to central variable of productivity model -human resource. Model components altogether explained 20 % of clinical nurses' productivity variance. This study found that the important component of productivity is human resources that are reciprocally related to other components of the model. Therefore, it can be stated that the managers can promote the productivity by using efficient strategies to correct human resource patterns.

  3. Energetics of molecular-beam epitaxy models

    NASA Technical Reports Server (NTRS)

    Krishnamurthy, Srinivasan; Berding, M. A.; Sher, A.; Chen, A.-B.

    1990-01-01

    The removal energies of constituent atoms from various unreconstructed semiconductor surfaces are calculated using a Green function method. An efficient difference-equation approach within the second-neighbor tight-binding model is employed. For a compound AB, binding energies for the A and B atoms on the (111), (-1 -1 -1), (100), and (110) surfaces are calculated. Analyses are made of the energy to remove an atom from the nearly full surface and from the nearly empty surface. Results are presented for Si, GaAs, CdTe, and HgTe; and the surface sublimation energies are found to depend on surface coverage and do not display a simple linear relationship to the number of bonds broken, as is often assumed in modeling growth by MBE.

  4. A molecular model for sporadic human aneuploidy.

    PubMed

    Warren, William D; Gorringe, Kylie L

    2006-04-01

    Aneuploidy is a leading cause of birth defects and a significant contributor to infertility in humans. Maternal age is the only well-established risk factor for gametic aneuploidy in the general population, with the underlying cause(s) yet to be identified. Here we present an extension of the 'two-hit' model for sporadic human aneuploidy. An important implication of this model is that the genetic makeup of an individual will influence the threshold where recombinationally at-risk oocytes (hit-1 events) become sensitive to the effects of advancing age (hit-2 events). Consequently, the age-related risk of gametic aneuploidy in many individuals is likely to differ significantly from the population average, and single nucleotide polymorphisms (SNPs) associated with altered risk should be identifiable.

  5. INVESTIGATIONS INTO MOLECULAR PATHWAYS IN THE POST GENOME ERA: CROSS SPECIES COMPARATIVE GENOMICS APPROACH

    EPA Science Inventory


    Genome sequencing efforts in the past decade were aimed at generating draft sequences of many prokaryotic and eukaryotic model organisms. Successful completion of unicellular eukaryotes, worm, fly and human genome have opened up the new field of molecular biology and function...

  6. Zebrafish as a Model to Investigate CNS Myelination

    PubMed Central

    Preston, Marnie A.; Macklin, Wendy B.

    2015-01-01

    Myelin plays a critical role in proper neuronal function by providing trophic and metabolic support to axons and facilitating energy-efficient saltatory conduction. Myelination is influenced by numerous molecules including growth factors, hormones, transmembrane receptors and extracellular molecules, which activate signaling cascades that drive cellular maturation. Key signaling molecules and downstream signaling cascades controlling myelination have been identified in cell culture systems. However, in vitro systems are not able to faithfully replicate the complex in vivo signaling environment that occurs during development or following injury. Currently, it remains time-consuming and expensive to investigate myelination in vivo in rodents, the most widely used model for studying mammalian myelination. As such, there is a need for alternative in vivo myelination models, particularly ones that can test molecular mechanisms without removing oligodendrocyte lineage cells from their native signaling environment or disrupting intercellular interactions with other cell types present during myelination. Here, we review the ever-increasing role of zebrafish in studies uncovering novel mechanisms controlling vertebrate myelination. These innovative studies range from observations of the behavior of single cells during in vivo myelination as well as mutagenesis- and pharmacology-based screens in whole animals. Additionally, we discuss recent efforts to develop novel models of demyelination and oligodendrocyte cell death in adult zebrafish for the study of cellular behavior in real time during repair and regeneration of damaged nervous systems. PMID:25263121

  7. The emerging role of cloud computing in molecular modelling.

    PubMed

    Ebejer, Jean-Paul; Fulle, Simone; Morris, Garrett M; Finn, Paul W

    2013-07-01

    There is a growing recognition of the importance of cloud computing for large-scale and data-intensive applications. The distinguishing features of cloud computing and their relationship to other distributed computing paradigms are described, as are the strengths and weaknesses of the approach. We review the use made to date of cloud computing for molecular modelling projects and the availability of front ends for molecular modelling applications. Although the use of cloud computing technologies for molecular modelling is still in its infancy, we demonstrate its potential by presenting several case studies. Rapid growth can be expected as more applications become available and costs continue to fall; cloud computing can make a major contribution not just in terms of the availability of on-demand computing power, but could also spur innovation in the development of novel approaches that utilize that capacity in more effective ways.

  8. An Investigation of Human Performance Model Validation

    DTIC Science & Technology

    2005-03-01

    from both models and empirical activities, and the construction of scenarios that will sufficiently exercise model and human participants. 1 Development...Soar to represent peripheral players/platforms in simulation-based exercises that are used to evaluate system design concepts and tactics.) We expect...and operational concepts can best be employed to assist them." As noted above, models used in the JSB exercise must be highly accurate and accredited

  9. Nondynamical correlation energy in model molecular systems

    NASA Astrophysics Data System (ADS)

    Chojnacki, Henryk

    The hypersurfaces for the deprotonation processes have been studied at the nonempirical level for H3O+, NH+4, PH+4, and H3S+ cations within their correlation consistent basis set. The potential energy curves were calculated and nondynamical correlation energies analyzed. We have found that the restricted Hartree-Fock wavefunction leads to the improper dissociation limit and, in the three latest cases requires multireference description. We conclude that these systems may be treated as a good models for interpretation of the proton transfer mechanism as well as for testing one-determinantal or multireference cases.

  10. The Methylazoxymethanol Acetate (MAM-E17) Rat Model: Molecular and Functional Effects in the Hippocampus

    PubMed Central

    Hradetzky, Eva; Sanderson, Thomas M; Tsang, Tsz M; Sherwood, John L; Fitzjohn, Stephen M; Lakics, Viktor; Malik, Nadia; Schoeffmann, Stephanie; O'Neill, Michael J; Cheng, Tammy MK; Harris, Laura W; Rahmoune, Hassan; Guest, Paul C; Sher, Emanuele; Collingridge, Graham L; Holmes, Elaine; Tricklebank, Mark D; Bahn, Sabine

    2012-01-01

    Administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM) on embryonic day 17 (E17) produces behavioral and anatomical brain abnormalities, which model some aspects of schizophrenia. This has lead to the premise that MAM rats are a neurodevelopmental model for schizophrenia. However, the underlying molecular pathways affected in this model have not been elucidated. In this study, we investigated the molecular phenotype of adult MAM rats by focusing on the frontal cortex and hippocampal areas, as these are known to be affected in schizophrenia. Proteomic and metabonomic analyses showed that the MAM treatment on E17 resulted primarily in deficits in hippocampal glutamatergic neurotransmission, as seen in some schizophrenia patients. Most importantly, these results were consistent with our finding of functional deficits in glutamatergic neurotransmission, as identified using electrophysiological recordings. Thus, this study provides the first molecular evidence, combined with functional validation, that the MAM-E17 rat model reproduces hippocampal deficits relevant to the pathology of schizophrenia. PMID:21956444

  11. 2D IR spectra of cyanide in water investigated by molecular dynamics simulations

    USGS Publications Warehouse

    Lee, Myung Won; Carr, Joshua K.; Göllner, Michael; Hamm, Peter; Meuwly, Markus

    2013-01-01

    Using classical molecular dynamics simulations, the 2D infrared (IR) spectroscopy of CN− solvated in D2O is investigated. Depending on the force field parametrizations, most of which are based on multipolar interactions for the CN− molecule, the frequency-frequency correlation function and observables computed from it differ. Most notably, models based on multipoles for CN− and TIP3P for water yield quantitatively correct results when compared with experiments. Furthermore, the recent finding that T 1 times are sensitive to the van der Waals ranges on the CN− is confirmed in the present study. For the linear IR spectrum, the best model reproduces the full widths at half maximum almost quantitatively (13.0 cm−1 vs. 14.9 cm−1) if the rotational contribution to the linewidth is included. Without the rotational contribution, the lines are too narrow by about a factor of two, which agrees with Raman and IR experiments. The computed and experimental tilt angles (or nodal slopes) α as a function of the 2D IR waiting time compare favorably with the measured ones and the frequency fluctuation correlation function is invariably found to contain three time scales: a sub-ps, 1 ps, and one on the 10-ps time scale. These time scales are discussed in terms of the structural dynamics of the surrounding solvent and it is found that the longest time scale (≈10 ps) most likely corresponds to solvent exchange between the first and second solvation shell, in agreement with interpretations from nuclear magnetic resonance measurements.

  12. Development of Laser Desorption Imaging Mass Spectrometry Methods to Investigate the Molecular Composition of Latent Fingermarks

    NASA Astrophysics Data System (ADS)

    Lauzon, Nidia; Dufresne, Martin; Chauhan, Vinita; Chaurand, Pierre

    2015-06-01

    For a century, fingermark analysis has been one of the most important and common methods in forensic investigations. Modern chemical analysis technologies have added the potential to determine the molecular composition of fingermarks and possibly identify chemicals a suspect may have come into contact with. Improvements in analytical detection of the molecular composition of fingermarks is therefore of great importance. In this regard, matrix-assisted laser desorption ionization (MALDI) and laser desorption ionization (LDI) imaging mass spectrometry (IMS) have proven to be useful technologies for fingermark analysis. In these analyses, the choice of ionizing agent and its mode of deposition are critical steps for the identification of molecular markers. Here we propose two novel and complementary IMS approaches for endogenous and exogenous substance detection in fingermarks: sublimation of 2-mercaptobenzothiazol (2-MBT) matrix and silver sputtering.

  13. A general two-cycle network model of molecular motors

    NASA Astrophysics Data System (ADS)

    Zhang, Yunxin

    2009-09-01

    Molecular motors are single macromolecules that generate forces at the piconewton range and nanometer scale. They convert chemical energy into mechanical work by moving along filamentous structures. In this paper, we study the velocity of two-head molecular motors in the framework of a mechanochemical network theory. The network model, a generalization of the recently work of Liepelt and Lipowsky [Steffen Liepelt, Reinhard Lipowsky, Kinesins network of chemomechanical motor cycles, Physical Review Letters 98 (25) (2007) 258102], is based on the discrete mechanochemical states of a molecular motor with multiple cycles. By generalizing the mathematical method developed by Fisher and Kolomeisky for a single cycle motor [Michael E. Fisher, Anatoly B. Kolomeisky, Simple mechanochemistry describes the dynamics of kinesin molecules, Proceedings of the National Academy of Sciences 98 (14) (2001) 7748-7753], we are able to obtain an explicit formula for the velocity of a molecular motor.

  14. Molecular cluster model for magnetic iron

    NASA Astrophysics Data System (ADS)

    Pavo, A. C.; Taft, C. A.; Hammond, B. L.; Lester, W. A., Jr.

    1989-08-01

    Ab initio Hartree-Fock calculations were performed on the quintet spin state of the Fe2 molecule in order to study the electronic, magnetic, and chemical bonding properties as well as the hyperfine interactions. Good agreement is found with band-theoretical and experimental parameters. The calculations support Pauling's model of occupation and bonding of valence orbitals, resonance of covalent bonds, and conduction-band metallic orbitals. A strong charge-polarization effect is found that is not observed in the septet ground state. The participation of s and d electrons in bonding is similar to that found in recent configuration-interaction (CI) calculations on the ground state. The calculated magneton number is in good agreement with experiment.

  15. Quantum interference in thermoelectric molecular junctions: A toy model perspective

    SciTech Connect

    Nozaki, Daijiro E-mail: research@nano.tu-dresden.de; Avdoshenko, Stas M.; Sevinçli, Hâldun; Cuniberti, Gianaurelio

    2014-08-21

    Quantum interference (QI) phenomena between electronic states in molecular circuits offer a new opportunity to design new types of molecular devices such as molecular sensors, interferometers, and thermoelectric devices. Controlling the QI effect is a key challenge for such applications. For the development of single molecular devices employing QI effects, a systematic study of the relationship between electronic structure and the quantum interference is needed. In order to uncover the essential topological requirements for the appearance of QI effects and the relationship between the QI-affected line shape of the transmission spectra and the electronic structures, we consider a homogeneous toy model where all on-site energies are identical and model four types of molecular junctions due to their topological connectivities. We systematically analyze their transmission spectra, density of states, and thermoelectric properties. Even without the degree of freedom for on-site energies an asymmetric Fano peak could be realized in the homogeneous systems with the cyclic configuration. We also calculate the thermoelectric properties of the model systems with and without fluctuation of on-site energies. Even under the fluctuation of the on-site energies, the finite thermoelectrics are preserved for the Fano resonance, thus cyclic configuration is promising for thermoelectric applications. This result also suggests the possibility to detect the cyclic configuration in the homogeneous systems and the presence of the QI features from thermoelectric measurements.

  16. VCMM: a visual tool for continuum molecular modeling.

    PubMed

    Bai, Shiyang; Lu, Benzhuo

    2014-05-01

    This paper describes the design and function of a visualization tool, VCMM, for visualizing and analyzing data, and interfacing solvers for generic continuum molecular modeling. In particular, an emphasis of the program is to treat the data set based on unstructured mesh as used in finite/boundary element simulations, which largely enhances the capabilities of current visualization tools in this area that only support structured mesh. VCMM is segmented into molecular, meshing and numerical modules. The capabilities of molecular module include molecular visualization and force field assignment. Meshing module contains mesh generation, analysis and visualization tools. Numerical module currently provides a few finite/boundary element solvers of continuum molecular modeling, and contains several common visualization tools for the numerical result such as line and plane interpolations, surface probing, volume rendering and stream rendering. Three modules can exchange data with each other and carry out a complete process of modeling. Interfaces are also designed in order to facilitate usage of other mesh generation tools and numerical solvers. We develop a technique to accelerate data retrieval and have combined many graphical techniques in visualization. VCMM is highly extensible, and users can obtain more powerful functions by introducing relevant plug-ins. VCMM can also be useful in other fields such as computational quantum chemistry, image processing, and material science.

  17. Interaction of methotrexate with trypsin analyzed by spectroscopic and molecular modeling methods

    NASA Astrophysics Data System (ADS)

    Wang, Yanqing; Zhang, Hongmei; Cao, Jian; Zhou, Qiuhua

    2013-11-01

    Trypsin is one of important digestive enzymes that have intimate correlation with human health and illness. In this work, the interaction of trypsin with methotrexate was investigated by spectroscopic and molecular modeling methods. The results revealed that methotrexate could interact with trypsin with about one binding site. Methotrexate molecule could enter into the primary substrate-binding pocket, resulting in inhibition of trypsin activity. Furthermore, the thermodynamic analysis implied that electrostatic force, hydrogen bonding, van der Waals and hydrophobic interactions were the main interactions for stabilizing the trypsin-methotrexate system, which agreed well with the results from the molecular modeling study.

  18. Simple Validation of Transient Plume Models Using Molecular Beam-Related Applications

    SciTech Connect

    Woronowicz, M. S.

    2008-12-31

    A simple effort using molecular beam data to compare the results of two different transient free molecule point source models was performed, motivated by a desire to determine the utility of such formulations for a variety of time-dependent applications. These models are evaluated against effusive molecular beam time-of-flight data, as well as behavior observed in pulsed laser ablation experiments and high-fidelity direct simulation Monte Carlo results. Such comparisons indicate that the physical behavior of these time-dependent expansions require taking a surface-enforced directional bias into account. This bias has been absent in a number of investigative formulations, both historical and current.

  19. Molecular interactions of organic molecules at the air/water interface investigated by sum frequency generation vibrational spectroscopy.

    PubMed

    Wang, Wenting; Ye, Shuji

    2017-02-08

    The molecular structure and dynamics of organic molecules at the aqueous interface have attracted a number of investigations owing to their importance and specific nature. However, there are relatively few studies on the direct characterization of the molecular interactions at the air/water interface because they are extremely difficult to measure in experiments. In this study, we use dibutyl ester molecules (R1CO2R2O2CR1) as a model of organic molecules, and investigate their molecular structure and interactions using sum frequency generation vibrational spectroscopy. We demonstrate that the molecular interactions can be estimated by measuring the intensity ratio of the symmetric stretching (ν1) and Fermi resonant bands (2ν2) of methyl groups. Here, dibutyl ester molecules are widely used as plasticizers in polymers to improve the properties of the plastics and polymers. It is found that the orientation angles of the tailed methyl groups at the air/water interface decrease from 34° to 19° when the chain length of R2 increases from 0 to 8. The total intermolecular interactions of the dibutyl ester molecules decrease as the chain length of R2 increases because the van der Waals interactions between the hydrocarbon chains increase, while the hydrogen bond interactions between the carbonyl group and water molecules decrease. Our study demonstrates the stability of ester-based plasticizers in polymers can be well predicted from the intensity ratio of the ν1 and 2ν2 bands of methyl group. Such an intensity ratio can be thus used as an effective vibrational optical ruler for characterizing molecular interactions between plasticizers and polymers.

  20. Molecular interaction of ctDNA and HSA with sulfadiazine sodium by multispectroscopic methods and molecular modeling.

    PubMed

    Geng, Shaoguang; Liu, Guosheng; Li, Wei; Cui, Fengling

    2013-01-01

    Interactions of sulfadiazine sodium (SD-Na) with calf thymus DNA (ctDNA) and human serum albumin (HSA) were studied using fluorescence spectroscopy, UV absorption spectroscopy and molecular modeling. The fluorescence experiments showed that the processes were static quenching. The results of UV spectra and molecular modeling of the interaction between SD-Na and ctDNA indicated that the binding mode might be groove binding. In addition, the interaction of SD-Na with HSA under simulative physiological conditions was also investigated. The binding constants (K) and the number of binding sites (n) at different temperatures (292, 302, 312 K) were 5.23 × 10(3) L/mol, 2.18; 4.50 × 10(3) L/mol, 2.35; and 4.08 × 10(3) L/mol, 2.47, respectively. Thermodynamic parameters including enthalpy change (ΔH) and entropy change (ΔS) were calculated, the results suggesting that hydrophobic force played a very important role in SD-Na binding to HSA, which was in good agreement with the molecular modeling study. Moreover, the effect of SD-Na on the conformation of HSA was analyzed using three-dimensional fluorescence spectra.

  1. The Immediate Exchange model: an analytical investigation

    NASA Astrophysics Data System (ADS)

    Katriel, Guy

    2015-01-01

    We study the Immediate Exchange model, recently introduced by Heinsalu and Patriarca [Eur. Phys. J. B 87, 170 (2014)], who showed by simulations that the wealth distribution in this model converges to a Gamma distribution with shape parameter 2. Here we justify this conclusion analytically, in the infinite-population limit. An infinite-population version of the model is derived, describing the evolution of the wealth distribution in terms of iterations of a nonlinear operator on the space of probability densities. It is proved that the Gamma distributions with shape parameter 2 are fixed points of this operator, and that, starting with an arbitrary wealth distribution, the process converges to one of these fixed points. We also discuss the mixed model introduced in the same paper, in which exchanges are either bidirectional or unidirectional with fixed probability. We prove that, although, as found by Heinsalu and Patriarca, the equilibrium distribution can be closely fit by Gamma distributions, the equilibrium distribution for this model is not a Gamma distribution.

  2. First principles modelling of contact resistance in molecular electronic devices.

    NASA Astrophysics Data System (ADS)

    Stokbro, Kurt; Taylor, Jeremy; Brandbyge, Mads

    2002-03-01

    We have used the TranSIESTA package[1,2] to investigate the contact resistance of gold-thiol bonds. The TranSIESTA package is a new density functional code employing local basis sets[3], combined with a non-equilibrium Greens function transport scheme. With this package we can calculate the selfconsistent electronic structure of a nanostructure coupled to 3-dimensional electrodes with different electrochemical potentials, using the same level of model chemistry for the electrodes as for the nanostructure. We have used the method to calculate the electron transport through DiThiol-Benzene (DTB) connected to gold electrodes. The transport properties have been calculated for a range of different molecule-electrode couplings, and I will discuss the influence of the coupling on the molecular conductance, and compare with experimental data. [1] M. Brandbyge, K. Stokbro, J. Taylor, J. L. Mozos, P. Ordejon, Material Research Society symposium proceedings volume 636, D9.25 (2000). [2] M. Brandbyge, K. Stokbro, J. Taylor, J. L. Mozos, P. Ordejon, Condmat 0110650 [3] SIESTA: D. Sanchez-Portal, P. Ordejon, E. Artacho and J. Soler, Int. J. Quantum Chem. 65, 453 (1997).

  3. A molecular dynamics model for the Coulomb explosion

    NASA Astrophysics Data System (ADS)

    Smith, Roger; Ramasawmy, D.; Kenny, S. D.

    2005-01-01

    The impact of positively charged Arn+ ions, n = 1, 4, 8, incident normally on the (1 0 0) surface of NaCl is studied by Molecular Dynamics (MD) simulations for energies up to 1 keV. The model assumes fixed charges on the ions and the effect of projectile charge is investigated as a function of energy. It is shown that there is a significant enhancement in the sputtering yield at low impact energies due to the attachment of Cl ions to the impacting Ar, which is subsequently ejected from the lattice. The low energy Ar ions can also experience acceleration towards the NaCl crystal due to Coulombic attraction. At energies greater than a few hundred eV the Ar ions implant within the crystal which accommodates the extra charge from these ions. As a result the sputtering yield from the initial impact is reduced but as the dose increases, the yield rises as Na+ ions are preferentially ejected from the lattice. A large proportion of the ejected material is in the form of clusters.

  4. Early molecular investigations of lichen-forming symbionts: 1986-2001*.

    PubMed

    DePriest, Paula T

    2004-01-01

    From the mid-1980s the symbionts in lichen associations, heterotrophic fungi and photosynthetic algae or cyanobacteria, were the subject of increasing numbers of molecular investigations. Many of the studies examined the phylogenetic placement of the individual symbiotic partners with their free-living relatives, refining their nomenclature and classification. Resulting phylogenies permitted the mapping of transitions to and from lichenization and stimulated discussion of the relative ease of gaining and losing symbiotic lifestyles. Comparing symbiont phylogenies both rejected strict cospeciation and mirrored phylogenies and hinted at more complex forces of coevolution, including symbiont switching and selection. Studies at the species and population levels examined patterns of species delimitation and geographic dispersion and processes such as gene flow, self-fertilization, and founder effect. Significant genetic variation often was associated with mobile elements, group I and spliceosomal introns. This review examines the influence of molecular investigation on lichenology during this first 15 years.

  5. Molecular identification of blow flies recovered from human cadavers during crime scene investigations in Malaysia.

    PubMed

    Kavitha, Rajagopal; Nazni, Wasi Ahmad; Tan, Tian Chye; Lee, Han Lim; Isa, Mohd Noor Mat; Azirun, Mohd Sofian

    2012-12-01

    Forensic entomology applies knowledge about insects associated with decedent in crime scene investigation. It is possible to calculate a minimum postmortem interval (PMI) by determining the age and species of the oldest blow fly larvae feeding on decedent. This study was conducted in Malaysia to identify maggot specimens collected during crime scene investigations. The usefulness of the molecular and morphological approach in species identifications was evaluated in 10 morphologically identified blow fly larvae sampled from 10 different crime scenes in Malaysia. The molecular identification method involved the sequencing of a total length of 2.2 kilo base pairs encompassing the 'barcode' fragments of the mitochondrial cytochrome oxidase I (COI), cytochrome oxidase II (COII) and t-RNA leucine genes. Phylogenetic analyses confirmed the presence of Chrysomya megacephala, Chrysomya rufifacies and Chrysomya nigripes. In addition, one unidentified blow fly species was found based on phylogenetic tree analysis.

  6. United polarizable multipole water model for molecular mechanics simulation

    PubMed Central

    Qi, Rui; Wang, Lee-Ping; Wang, Qiantao; Pande, Vijay S.; Ren, Pengyu

    2015-01-01

    We report the development of a united AMOEBA (uAMOEBA) polarizable water model, which is computationally 3–5 times more efficient than the three-site AMOEBA03 model in molecular dynamics simulations while providing comparable accuracy for gas-phase and liquid properties. In this coarse-grained polarizable water model, both electrostatic (permanent and induced) and van der Waals representations have been reduced to a single site located at the oxygen atom. The permanent charge distribution is described via the molecular dipole and quadrupole moments and the many-body polarization via an isotropic molecular polarizability, all located at the oxygen center. Similarly, a single van der Waals interaction site is used for each water molecule. Hydrogen atoms are retained only for the purpose of defining local frames for the molecular multipole moments and intramolecular vibrational modes. The parameters have been derived based on a combination of ab initio quantum mechanical and experimental data set containing gas-phase cluster structures and energies, and liquid thermodynamic properties. For validation, additional properties including dimer interaction energy, liquid structures, self-diffusion coefficient, and shear viscosity have been evaluated. The results demonstrate good transferability from the gas to the liquid phase over a wide range of temperatures, and from nonpolar to polar environments, due to the presence of molecular polarizability. The water coordination, hydrogen-bonding structure, and dynamic properties given by uAMOEBA are similar to those derived from the all-atom AMOEBA03 model and experiments. Thus, the current model is an accurate and efficient alternative for modeling water. PMID:26156485

  7. United polarizable multipole water model for molecular mechanics simulation

    SciTech Connect

    Qi, Rui; Wang, Qiantao; Ren, Pengyu; Wang, Lee-Ping; Pande, Vijay S.

    2015-07-07

    We report the development of a united AMOEBA (uAMOEBA) polarizable water model, which is computationally 3–5 times more efficient than the three-site AMOEBA03 model in molecular dynamics simulations while providing comparable accuracy for gas-phase and liquid properties. In this coarse-grained polarizable water model, both electrostatic (permanent and induced) and van der Waals representations have been reduced to a single site located at the oxygen atom. The permanent charge distribution is described via the molecular dipole and quadrupole moments and the many-body polarization via an isotropic molecular polarizability, all located at the oxygen center. Similarly, a single van der Waals interaction site is used for each water molecule. Hydrogen atoms are retained only for the purpose of defining local frames for the molecular multipole moments and intramolecular vibrational modes. The parameters have been derived based on a combination of ab initio quantum mechanical and experimental data set containing gas-phase cluster structures and energies, and liquid thermodynamic properties. For validation, additional properties including dimer interaction energy, liquid structures, self-diffusion coefficient, and shear viscosity have been evaluated. The results demonstrate good transferability from the gas to the liquid phase over a wide range of temperatures, and from nonpolar to polar environments, due to the presence of molecular polarizability. The water coordination, hydrogen-bonding structure, and dynamic properties given by uAMOEBA are similar to those derived from the all-atom AMOEBA03 model and experiments. Thus, the current model is an accurate and efficient alternative for modeling water.

  8. United polarizable multipole water model for molecular mechanics simulation

    NASA Astrophysics Data System (ADS)

    Qi, Rui; Wang, Lee-Ping; Wang, Qiantao; Pande, Vijay S.; Ren, Pengyu

    2015-07-01

    We report the development of a united AMOEBA (uAMOEBA) polarizable water model, which is computationally 3-5 times more efficient than the three-site AMOEBA03 model in molecular dynamics simulations while providing comparable accuracy for gas-phase and liquid properties. In this coarse-grained polarizable water model, both electrostatic (permanent and induced) and van der Waals representations have been reduced to a single site located at the oxygen atom. The permanent charge distribution is described via the molecular dipole and quadrupole moments and the many-body polarization via an isotropic molecular polarizability, all located at the oxygen center. Similarly, a single van der Waals interaction site is used for each water molecule. Hydrogen atoms are retained only for the purpose of defining local frames for the molecular multipole moments and intramolecular vibrational modes. The parameters have been derived based on a combination of ab initio quantum mechanical and experimental data set containing gas-phase cluster structures and energies, and liquid thermodynamic properties. For validation, additional properties including dimer interaction energy, liquid structures, self-diffusion coefficient, and shear viscosity have been evaluated. The results demonstrate good transferability from the gas to the liquid phase over a wide range of temperatures, and from nonpolar to polar environments, due to the presence of molecular polarizability. The water coordination, hydrogen-bonding structure, and dynamic properties given by uAMOEBA are similar to those derived from the all-atom AMOEBA03 model and experiments. Thus, the current model is an accurate and efficient alternative for modeling water.

  9. Molecular structural investigation of adenosine using spectroscopic and quantum computational calculations

    NASA Astrophysics Data System (ADS)

    Bakkiyaraj, D.; Periandy, S.; Xavier, S.

    2016-09-01

    In this study; spectroscopic investigation of adenosine having clinical importance was studied computationally and obtained results were compared with experimental ones. In this scope, geometric optimization and conformational analysis were studied and vibrational spectroscopic properties were studied on the most stable form. NMR and TD-DFT studies on the title compound were conducted with its experimental data. In addition atomic charge distribution, NBO, frontier molecular analysis, thermodynamic analysis and hyperpolarization features were studied.

  10. Promoting Representational Competence with Molecular Models in Organic Chemistry

    ERIC Educational Resources Information Center

    Stull, Andrew T.; Gainer, Morgan; Padalkar, Shamin; Hegarty, Mary

    2016-01-01

    Mastering the many different diagrammatic representations of molecules used in organic chemistry is challenging for students. This article summarizes recent research showing that manipulating 3-D molecular models can facilitate the understanding and use of these representations. Results indicate that students are more successful in translating…

  11. The Use of Molecular Modeling Programs in Medicinal Chemistry Instruction.

    ERIC Educational Resources Information Center

    Harrold, Marc W.

    1992-01-01

    This paper describes and evaluates the use of a molecular modeling computer program (Alchemy II) in a pharmaceutical education program. Provided are the hardware requirements and basic program features as well as several examples of how this program and its features have been applied in the classroom. (GLR)

  12. Fischer and Schrock Carbene Complexes: A Molecular Modeling Exercise

    ERIC Educational Resources Information Center

    Montgomery, Craig D.

    2015-01-01

    An exercise in molecular modeling that demonstrates the distinctive features of Fischer and Schrock carbene complexes is presented. Semi-empirical calculations (PM3) demonstrate the singlet ground electronic state, restricted rotation about the C-Y bond, the positive charge on the carbon atom, and hence, the electrophilic nature of the Fischer…

  13. Pure and Modified Co-Poly(amide-12-b-ethylene oxide) Membranes for Gas Separation Studied by Molecular Investigations

    PubMed Central

    De Lorenzo, Luana; Tocci, Elena; Gugliuzza, Annarosa; Drioli, Enrico

    2012-01-01

    This paper deals with a theoretical investigation of gas transport properties in a pure and modified PEBAX block copolymer membrane with N-ethyl-o/p-toluene sulfonamide (KET) as additive molecules. Molecular dynamics simulations using COMPASS force field, Gusev-Suter Transition State Theory (TST) and Monte Carlo methods were used. Bulk models of PEBAX and PEBAX/KET in different copolymer/additive compositions were assembled and analyzed to evaluate gas permeability and morphology to characterize structure-performance relationships. PMID:24958285

  14. Investigating Nitrogen Pollution: Activities and Models.

    ERIC Educational Resources Information Center

    Green Teacher, 2000

    2000-01-01

    Introduces activities on nitrogen, nitrogen pollution from school commuters, nitrogen response in native and introduced species, and nutrient loading models. These activities help students determine the nitrogen contribution from their parents' cars, test native plant responses to nitrogen, and experiment with the results of removing water from…

  15. Markov models of molecular kinetics: generation and validation.

    PubMed

    Prinz, Jan-Hendrik; Wu, Hao; Sarich, Marco; Keller, Bettina; Senne, Martin; Held, Martin; Chodera, John D; Schütte, Christof; Noé, Frank

    2011-05-07

    Markov state models of molecular kinetics (MSMs), in which the long-time statistical dynamics of a molecule is approximated by a Markov chain on a discrete partition of configuration space, have seen widespread use in recent years. This approach has many appealing characteristics compared to straightforward molecular dynamics simulation and analysis, including the potential to mitigate the sampling problem by extracting long-time kinetic information from short trajectories and the ability to straightforwardly calculate expectation values and statistical uncertainties of various stationary and dynamical molecular observables. In this paper, we summarize the current state of the art in generation and validation of MSMs and give some important new results. We describe an upper bound for the approximation error made by modeling molecular dynamics with a MSM and we show that this error can be made arbitrarily small with surprisingly little effort. In contrast to previous practice, it becomes clear that the best MSM is not obtained by the most metastable discretization, but the MSM can be much improved if non-metastable states are introduced near the transition states. Moreover, we show that it is not necessary to resolve all slow processes by the state space partitioning, but individual dynamical processes of interest can be resolved separately. We also present an efficient estimator for reversible transition matrices and a robust test to validate that a MSM reproduces the kinetics of the molecular dynamics data.

  16. Gradient Models in Molecular Biophysics: Progress, Challenges, Opportunities

    PubMed Central

    Bardhan, Jaydeep P.

    2014-01-01

    In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g. molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding features such as nonlocal dielectric response, and nonlinearities resulting from dielectric saturation. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost forty years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The paper concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics. PMID:25505358

  17. Gradient models in molecular biophysics: progress, challenges, opportunities

    NASA Astrophysics Data System (ADS)

    Bardhan, Jaydeep P.

    2013-12-01

    In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g., molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding nonlocal dielectric response. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain, and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost 40 years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The review concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics.

  18. An investigation of the preparation of high molecular weight perfluorocarbon polyethers

    NASA Technical Reports Server (NTRS)

    Watts, R. O.; Tarrant, P.

    1972-01-01

    High molecular weight perfluorocarbon polyether gums were obtained by photolysis of perfluorodienes and discyl fluorides containing a perfluorocarbon polyether backbond. The materials obtained are represented by chemical formulas. A method was developed whereby reactive acyl fluoride and trifluorovinyl end groups are converted into inert structures. In order to investigate the possible preparation of difunctional molecules which may be useful in polymer synthesis, the reactions of hexafluoropropene oxide (HFPO) with Grignard and organolithium reagents have been studied. Reactions of various nucleophilic reagents with HFPO were also investigated.

  19. A portable molecular beam epitaxy system for in situ x-ray investigations at synchrotron beamlines

    SciTech Connect

    Slobodskyy, T.; Schroth, P.; Grigoriev, D.; Minkevich, A. A.; Baumbach, T.; Hu, D. Z.; Schaadt, D. M.

    2012-10-15

    A portable synchrotron molecular beam epitaxy (MBE) system is designed and applied for in situ investigations. The growth chamber is equipped with all the standard MBE components such as effusion cells with shutters, main shutter, cooling shroud, manipulator, reflection high energy electron diffraction setup, and pressure gauges. The characteristic feature of the system is the beryllium windows which are used for in situ x-ray measurements. An UHV sample transfer case allows in vacuo transfer of samples prepared elsewhere. We describe the system design and demonstrate its performance by investigating the annealing process of buried InGaAs self-organized quantum dots.

  20. A portable molecular beam epitaxy system for in situ x-ray investigations at synchrotron beamlines.

    PubMed

    Slobodskyy, T; Schroth, P; Grigoriev, D; Minkevich, A A; Hu, D Z; Schaadt, D M; Baumbach, T

    2012-10-01

    A portable synchrotron molecular beam epitaxy (MBE) system is designed and applied for in situ investigations. The growth chamber is equipped with all the standard MBE components such as effusion cells with shutters, main shutter, cooling shroud, manipulator, reflection high energy electron diffraction setup, and pressure gauges. The characteristic feature of the system is the beryllium windows which are used for in situ x-ray measurements. An UHV sample transfer case allows in vacuo transfer of samples prepared elsewhere. We describe the system design and demonstrate its performance by investigating the annealing process of buried InGaAs self-organized quantum dots.

  1. Molecular polymorphism: microwave spectra, equilibrium structures, and an astronomical investigation of the HNCS isomeric family.

    PubMed

    McGuire, Brett A; Martin-Drumel, Marie-Aline; Thorwirth, Sven; Brünken, Sandra; Lattanzi, Valerio; Neill, Justin L; Spezzano, Silvia; Yu, Zhenhong; Zaleski, Daniel P; Remijan, Anthony J; Pate, Brooks H; McCarthy, Michael C

    2016-08-10

    The rotational spectra of thioisocyanic acid (HNCS), and its three energetic isomers (HSCN, HCNS, and HSNC) have been observed at high spectral resolution by a combination of chirped-pulse and Fabry-Pérot Fourier-transform microwave spectroscopy between 6 and 40 GHz in a pulsed-jet discharge expansion. Two isomers, thiofulminic acid (HCNS) and isothiofulminic acid (HSNC), calculated here to be 35-37 kcal mol(-1) less stable than the ground state isomer HNCS, have been detected for the first time. Precise rotational, centrifugal distortion, and nitrogen hyperfine coupling constants have been determined for the normal and rare isotopic species of both molecules; all are in good agreement with theoretical predictions obtained at the coupled cluster level of theory. On the basis of isotopic spectroscopy, precise molecular structures have been derived for all four isomers by correcting experimental rotational constants for the effects of rotation-vibration interaction calculated theoretically. Formation and isomerization pathways have also been investigated; the high abundance of HSCN relative to ground state HNCS, and the detection of strong lines of SH using CH3CN and H2S, suggest that HSCN is preferentially produced by the radical-radical reaction HS + CN. A radio astronomical search for HSCN and its isomers has been undertaken toward the high-mass star-forming region Sgr B2(N) in the Galactic Center with the 100 m Green Bank Telescope. While we find clear evidence for HSCN, only a tentative detection of HNCS is proposed, and there is no indication of HCNS or HSNC at the same rms noise level. HSCN, and tentatively HNCS, displays clear deviations from a single-excitation temperature model, suggesting weak masing may be occurring in some transitions in this source.

  2. Combustion of butanol isomers - A detailed molecular beam mass spectrometry investigation of their flame chemistry

    SciTech Connect

    Osswald, Patrick; Gueldenberg, Hanna; Kohse-Hoeinghaus, Katharina; Yang, Bin; Yuan, Tao; Qi, Fei

    2011-01-15

    The combustion chemistry of the four butanol isomers, 1-, 2-, iso- and tert-butanol was studied in flat, premixed, laminar low-pressure (40 mbar) flames of the respective alcohols. Fuel-rich ({phi} = 1.7) butanol-oxygen-(25%)argon flames were investigated using different molecular beam mass spectrometry (MBMS) techniques. Quantitative mole fraction profiles are reported as a function of burner distance. In total, 57 chemical compounds, including radical and isomeric species, have been unambiguously assigned and detected quantitatively in each flame using a combination of vacuum ultraviolet (VUV) photoionization (PI) and electron ionization (EI) MBMS. Synchrotron-based PI-MBMS allowed to separate isomeric combustion intermediates according to their different ionization thresholds. Complementary measurements in the same flames with a high mass-resolution EI-MBMS system provided the exact elementary composition of the involved species. Resulting mole fraction profiles from both instruments are generally in good quantitative agreement. In these flames of the four butanol isomers, temperature, measured by laser-induced fluorescence (LIF) of seeded nitric oxide, and major species profiles are strikingly similar, indicating seemingly analog global combustion behavior. However, significant variations in the intermediate species pool are observed between the fuels and discussed with respect to fuel-specific destruction pathways. As a consequence, different, fuel-specific pollutant emissions may be expected, by both their chemical nature and concentrations. The results reported here are the first of their kind from premixed isomeric butanol flames and are thought to be valuable for improving existing kinetic combustion models. (author)

  3. Memphis Harbor, Mississippi River: Model Investigation

    DTIC Science & Technology

    1950-12-01

    MEMORANDUM NO. 2 -320 CONDUCTED F OR THE PRESIDENT, MISSISSIPPI RIVER COMMISSION ARMY·MRC.VICKSBURG. MISS. CORPS OF ENGINEERS, U. S. ARMY BY...failing to comply with a collection of information if it does not display a currently valid OMB control number 1. REPORT DATE DEC 1950 2 . REPORT TYPE...second wrapper indorsement to Waterways Experiment Station letter dated 2 October 1946, subject: "Proposed Model Study, Presidents Island, Mississippi

  4. Molecular-orbital model for metal-sapphire interfacial strength

    NASA Technical Reports Server (NTRS)

    Johnson, K. H.; Pepper, S. V.

    1982-01-01

    Self-consistent-field X-Alpha scattered-wave cluster molecular-orbital models have been constructed for transition and noble metals (Fe, Ni, Cu, and Ag) in contact with a sapphire (Al2O3) surface. It is found that a chemical bond is established between the metal d-orbital electrons and the nonbonding 2p-orbital electrons of the oxygen anions on the Al2O3 surface. An increasing number of occupied metal-sapphire antibonding molecular orbitals explains qualitatively the observed decrease of contact shear strength through the series Fe, Ni, Cu, and Ag.

  5. Hidden Markov models from molecular dynamics simulations on DNA.

    PubMed

    Thayer, Kelly M; Beveridge, D L

    2002-06-25

    An enhanced bioinformatics tool incorporating the participation of molecular structure as well as sequence in protein DNA recognition is proposed and tested. Boltzmann probability models of sequence-dependent DNA structure from all-atom molecular dynamics simulations were obtained and incorporated into hidden Markov models (HMMs) that can recognize molecular structural signals as well as sequence in protein-DNA binding sites on a genome. The binding of catabolite activator protein (CAP) to cognate DNA sequences was used as a prototype case for implementation and testing of the method. The results indicate that even HMMs based on probabilistic roll/tilt dinucleotide models of sequence-dependent DNA structure have some capability to discriminate between known CAP binding and nonbinding sites and to predict putative CAP binding sites in unknowns. Restricting HMMs to sequence only in regions of strong consensus in which the protein makes base specific contacts with the cognate DNA further improved the discriminatory capabilities of the HMMs. Comparison of results with controls based on sequence only indicates that extending the definition of consensus from sequence to structure improves the transferability of the HMMs, and provides further supportive evidence of a role for dynamical molecular structure as well as sequence in genomic regulatory mechanisms.

  6. Multi-level molecular modelling for plasma medicine

    NASA Astrophysics Data System (ADS)

    Bogaerts, Annemie; Khosravian, Narjes; Van der Paal, Jonas; Verlackt, Christof C. W.; Yusupov, Maksudbek; Kamaraj, Balu; Neyts, Erik C.

    2016-02-01

    Modelling at the molecular or atomic scale can be very useful for obtaining a better insight in plasma medicine. This paper gives an overview of different atomic/molecular scale modelling approaches that can be used to study the direct interaction of plasma species with biomolecules or the consequences of these interactions for the biomolecules on a somewhat longer time-scale. These approaches include density functional theory (DFT), density functional based tight binding (DFTB), classical reactive and non-reactive molecular dynamics (MD) and united-atom or coarse-grained MD, as well as hybrid quantum mechanics/molecular mechanics (QM/MM) methods. Specific examples will be given for three important types of biomolecules, present in human cells, i.e. proteins, DNA and phospholipids found in the cell membrane. The results show that each of these modelling approaches has its specific strengths and limitations, and is particularly useful for certain applications. A multi-level approach is therefore most suitable for obtaining a global picture of the plasma-biomolecule interactions.

  7. Investigation of Terminal Group Effect on Electron Transport Through Open Molecular Structures

    NASA Astrophysics Data System (ADS)

    C. Preferencial, Kala; P. Aruna, Priya; John Thiruvadigal, D.

    2013-05-01

    The effect of terminal groups on the electron transport through metal-molecule-metal system has been investigated using nonequilibrium Green's function (NEGF) formalism combined with extended Huckel theory (EHT). Au-molecule-Au junctions are constructed with borazine and BCN unit structure as core molecule and sulphur (S), oxygen (O), selenium (Se) and cyano-group (CN) as terminal groups. The electron transport characteristics of the borazine and BCN molecular systems are analyzed through the transmission spectra and the current-voltage curve. The results demonstrate that the terminal groups modifying the transport behaviors of these systems in a controlled way. Our result shows that, selenium is the best linker to couple borazine to Au electrode and oxygen is the best one to couple BCN to Au electrode. Furthermore, the results of borazine systems are compared with that of BCN molecular systems and are discussed. Simulation results show that the conductance through BCN molecular systems is four times larger than the borazine molecular systems. Negative differential resistance behavior is observed with borazine-CN system and the saturation feature appears in BCN systems.

  8. Model investigation overthrows assumptions of watershed research

    NASA Astrophysics Data System (ADS)

    Schultz, Colin

    2012-04-01

    A 2009 study revealed serious flaws in a standard technique used by hydrological researchers to understand how changes in watershed land use affect stream flow behaviors, such as peak flows. The study caused academics and government agencies alike to rethink decades of watershed research and prompted Kuraś et al. to reinvestigate a number of long-standing assumptions in watershed research using a complex and well-validated computer model that accounts for a range of internal watershed dynamics and hydrologic processes. For the test site at 241 Creek in British Columbia, Canada, the authors found not only that deforestation increased the severity of floods but also that it had a scaling influence on both the magnitudes and frequencies of the floods. The model showed that the larger the flood, the more its magnitude was amplified by deforestation, with 10-to 100-year-return-period floods increasing in size by 9%-25%. Following a simulated removal of half of the watershed's trees, the authors found that 10-year-return-period floods occurred twice as often, while 100-year-return-period events became 5-6.7 times more frequent. This proportional relationship between the increase in flood magnitudes and frequencies following deforestation and the size of the flood runs counter to the prevailing wisdom in hydrological science.

  9. An Investigation of Item Fit Statistics for Mixed IRT Models

    ERIC Educational Resources Information Center

    Chon, Kyong Hee

    2009-01-01

    The purpose of this study was to investigate procedures for assessing model fit of IRT models for mixed format data. In this study, various IRT model combinations were fitted to data containing both dichotomous and polytomous item responses, and the suitability of the chosen model mixtures was evaluated based on a number of model fit procedures.…

  10. An Investigation of Goodness of Model Data Fit

    ERIC Educational Resources Information Center

    Onder, Ismail

    2007-01-01

    IRT models' advantages can only be realized when the model fits the data set of interest. Therefore, this study aimed to investigate which IRT model will provide the best fit to the data obtained from OZDEBYR OSS 2004 D-II Exam Science Test. In goodness-of-fit analysis, first the model assumptions and then the expected model features were checked.…

  11. Molecular orientation distributions during injection molding of liquid crystalline polymers: Ex situ investigation of partially filled moldings

    SciTech Connect

    Fang, Jun; Burghardt, Wesley R.; Bubeck, Robert A.

    2013-01-10

    The development of molecular orientation in thermotropic liquid crystalline polymers (TLCPs) during injection molding has been investigated using two-dimensional wide-angle X-ray scattering coordinated with numerical computations employing the Larson-Doi polydomain model. Orientation distributions were measured in 'short shot' moldings to characterize structural evolution prior to completion of mold filling, in both thin and thick rectangular plaques. Distinct orientation patterns are observed near the filling front. In particular, strong extension at the melt front results in nearly transverse molecular alignment. Far away from the flow front shear competes with extension to produce complex spatial distributions of orientation. The relative influence of shear is stronger in the thin plaque, producing orientation along the filling direction. Exploiting an analogy between the Larson-Doi model and a fiber orientation model, we test the ability of process simulation tools to predict TLCP orientation distributions during molding. Substantial discrepancies between model predictions and experimental measurements are found near the flow front in partially filled short shots, attributed to the limits of the Hele-Shaw approximation used in the computations. Much of the flow front effect is however 'washed out' by subsequent shear flow as mold filling progresses, leading to improved agreement between experiment and corresponding numerical predictions.

  12. Shocks, Superbubbles, and Filaments: Investigations into Large Scale Gas Motions in Giant Molecular Clouds

    NASA Astrophysics Data System (ADS)

    Pon, Andrew Richard

    2013-12-01

    Giant molecular clouds (GMCs), out of which stars form, are complex, dynamic systems, which both influence and are shaped by the process of star formation. In this dissertation, I examine three different facets of the dynamical motions within GMCs. Collapse modes in different dimensional objects. Molecular clouds contain lower dimensional substructures, such as filaments and sheets. The collapse properties of finite filaments and sheets differ from those of spherical objects as well as infinite sheets and filaments. I examine the importance of local collapse modes of small central perturbations, relative to global collapse modes, in different dimensional objects to elucidate whether strong perturbations are required for molecular clouds to fragment to form stars. I also calculate the dependence of the global collapse timescale upon the aspect ratio of sheets and filaments. I find that lower dimensional objects are more readily fragmented, and that for a constant density, lower dimensional objects and clouds with larger aspect ratios collapse more slowly. An edge-driven collapse mode also exists in sheets and filaments and is most important in elongated filaments. The failure to consider the geometry of a gas cloud is shown to lead to an overestimation of the star formation rate by up to an order of magnitude. Molecular tracers of turbulent energy dissipation. Molecular clouds contain supersonic turbulence that simulations predict will decay rapidly via shocks. I use shock models to predict which species emit the majority of the turbulent energy dissipated in shocks and find that carbon monoxide, CO, is primarily responsible for radiating away this energy. By combining these shock models with estimates for the turbulent energy dissipation rate of molecular clouds, I predict the expected shock spectra of CO from molecular clouds. I compare the results of these shock models to predictions for the emission from the unshocked gas in GMCs and show that mid

  13. Geometric investigations of a vorticity model equation

    NASA Astrophysics Data System (ADS)

    Bauer, Martin; Kolev, Boris; Preston, Stephen C.

    2016-01-01

    This article consists of a detailed geometric study of the one-dimensional vorticity model equation which is a particular case of the generalized Constantin-Lax-Majda equation. Wunsch showed that this equation is the Euler-Arnold equation on Diff (S1) when the latter is endowed with the right-invariant homogeneous H ˙ 1 / 2-metric. In this article we prove that the exponential map of this Riemannian metric is not Fredholm and that the sectional curvature is locally unbounded. Furthermore, we prove a Beale-Kato-Majda-type blow-up criterion, which we then use to demonstrate a link to our non-Fredholmness result. Finally, we extend a blow-up result of Castro-Córdoba to the periodic case and to a much wider class of initial conditions, using a new generalization of an inequality for Hilbert transforms due to Córdoba-Córdoba.

  14. Molecular dynamics studies of supercooled water using a monatomic model

    NASA Astrophysics Data System (ADS)

    Moore, Emily Brooke

    There remain many unanswered questions regarding the structure and behavior of water, particularly when cooled below the melting temperature into water's supercooled region. In this region, liquid water is metastable, and rapid crystallization makes it difficult to study experimentally the liquid and the crystallization process. Computational studies are hindered by the complexity of accurately modeling water and the computational cost of simulating processes such as crystallization. In this work, the development and validation of mW, a monatomic water model, is presented. This model is able to quantitatively reproduce the structure, dynamic anomalies and phase behavior of water without hydrogen atoms or electrostatics by reproducing water's propensity to form locally tetrahedral structures. Using the mW water model in molecular dynamics simulations, we show the evolution of the local structure of water from 300--100 K. We find that the thermodynamic and structural properties studied, density, tetrahedrality and structural correlation length, change maximally or are maximum at 202 +/- 2 K, the liquid-liquid transformation temperature. Shifting to water confined within cylindrical nanopores, we present the development of a rotationally invariant method, the CHILL algorithm, to distinguish between liquid, hexagonal and cubic ice. We analyze the process of homogeneous nucleation, growth and melting within hydrophilic pores, as well as the effect of water-pore interaction strength on the melting of ice and liquid-ice coexistence within pores. Crystallization within the nanopores results in cubic ice with hexagonal stacking faults in agreement with experiments. We also investigate crystallization of bulk liquid within water's experimentally inaccessible "no man's land." Crystallization occurs through rapid development of ice nuclei that grow and consolidate, precluding the measurement of diffusion within the liquid. Analysis of how ice structure develops shows that

  15. Investigation of Statistical Inference Methodologies Through Scale Model Propagation Experiments

    DTIC Science & Technology

    2015-09-30

    Investigation of Statistical Inference Methodologies Through Scale Model Propagation Experiments Jason D. Sagers Applied Research Laboratories...statistical inference methodologies for ocean-acoustic problems by investigating and applying statistical methods to data collected from scale -model...experiments over a translationally invariant wedge, (2) to plan and conduct 3D propagation experiments over the Hudson Canyon scale -model bathymetry, and (3

  16. SWIFT MODELLER: a Java based GUI for molecular modeling.

    PubMed

    Mathur, Abhinav; Shankaracharya; Vidyarthi, Ambarish S

    2011-10-01

    MODELLER is command line argument based software which requires tedious formatting of inputs and writing of Python scripts which most people are not comfortable with. Also the visualization of output becomes cumbersome due to verbose files. This makes the whole software protocol very complex and requires extensive study of MODELLER manuals and tutorials. Here we describe SWIFT MODELLER, a GUI that automates formatting, scripting and data extraction processes and present it in an interactive way making MODELLER much easier to use than before. The screens in SWIFT MODELLER are designed keeping homology modeling in mind and their flow is a depiction of its steps. It eliminates the formatting of inputs, scripting processes and analysis of verbose output files through automation and makes pasting of the target sequence as the only prerequisite. Jmol (3D structure visualization tool) has been integrated into the GUI which opens and demonstrates the protein data bank files created by the MODELLER software. All files required and created by the software are saved in a folder named after the work instance's date and time of execution. SWIFT MODELLER lowers the skill level required for the software through automation of many of the steps in the original software protocol, thus saving an enormous amount of time per instance and making MODELLER very easy to work with.

  17. Investigation of Y/SBA Composite Molecular Sieves Morphology Control and Catalytic Performance for n-Pentane Aromatization

    PubMed Central

    Shi, Chun-Wei; Wu, Wen-Yuan; Li, Shuai; Bian, Xue; Zhao, Shan-lin; Pei, Ming-Yuan

    2016-01-01

    Using Y molecular sieve as the core, Y/SBA-15 composite molecular sieves were prepared by different crystallization methods in the paper. The growth process and morphologies of the composite molecular sieves were controlled by adjusting the synthesis factors. The structures and acidity of two kinds of composite molecular sieves were characterized by X-ray diffraction (XRD), N2 adsorption/desorption, transmission electron microscopy (TEM), and NH3-TPD. The catalysis performances of the composite molecular sieves were investigated in the aromatization reaction of n-pentane. The results indicated that the desired core-shell composite molecular sieves were obtained when the crystallization conditions were 36 hours, 100 °C and secondary crystallization. The aromatization results showed that core-shell composite molecular sieves had better selectivity for producing high application value xylenes compared to mixed-crystal composite molecular sieves. PMID:27029526

  18. An ion mobility mass spectrometer for investigating photoisomerization and photodissociation of molecular ions.

    PubMed

    Adamson, B D; Coughlan, N J A; Markworth, P B; Continetti, R E; Bieske, E J

    2014-12-01

    An ion mobility mass spectrometry apparatus for investigating the photoisomerization and photodissociation of electrosprayed molecular ions in the gas phase is described. The device consists of a drift tube mobility spectrometer, with access for a laser beam that intercepts the drifting ion packet either coaxially or transversely, followed by a quadrupole mass filter. An ion gate halfway along the drift region allows the instrument to be used as a tandem ion mobility spectrometer, enabling mobility selection of ions prior to irradiation, with the photoisomer ions being separated over the second half of the drift tube. The utility of the device is illustrated with photoisomerization and photodissociation action spectra of carbocyanine molecular cations. The mobility resolution of the device for singly charged ions is typically 80 and it has a mass range of 100-440 Da, with the lower limit determined by the drive frequency for the ion funnels, and the upper limit by the quadrupole mass filter.

  19. An ion mobility mass spectrometer for investigating photoisomerization and photodissociation of molecular ions

    SciTech Connect

    Adamson, B. D.; Coughlan, N. J. A.; Markworth, P. B.; Bieske, E. J.; Continetti, R. E.

    2014-12-15

    An ion mobility mass spectrometry apparatus for investigating the photoisomerization and photodissociation of electrosprayed molecular ions in the gas phase is described. The device consists of a drift tube mobility spectrometer, with access for a laser beam that intercepts the drifting ion packet either coaxially or transversely, followed by a quadrupole mass filter. An ion gate halfway along the drift region allows the instrument to be used as a tandem ion mobility spectrometer, enabling mobility selection of ions prior to irradiation, with the photoisomer ions being separated over the second half of the drift tube. The utility of the device is illustrated with photoisomerization and photodissociation action spectra of carbocyanine molecular cations. The mobility resolution of the device for singly charged ions is typically 80 and it has a mass range of 100-440 Da, with the lower limit determined by the drive frequency for the ion funnels, and the upper limit by the quadrupole mass filter.

  20. Molecular arrangement investigation of copper phthalocyanine grown on hydrogen passivated Si(1 1 1) surfaces

    NASA Astrophysics Data System (ADS)

    Arbi, I.; Ben Hamada, B.; Souissi, A.; Menzli, S.; Ben Azzouz, C.; Laribi, A.; Akremi, A.; Chefi, C.

    2014-06-01

    Chemical, electronic and structural properties of ultra thin films of copper phthalocyanine (CuPc) grown on hydrogen passivated silicon (1 1 1) surfaces were investigated in situ by X-ray photoelectron spectroscopy (XPS), ultraviolet photoemission spectroscopy (UPS), X-ray photoelectron diffraction (XPD) and electron diffraction (LEED). The early stages of copper phthalocyanine adsorption (1-2) were characterized by the saturation of surface defects and by a flat lying disposition on the surface. Upon further CuPc coverage, the passivation of Si surfaces resulted in the molecule taking a standing position in films. The molecular packing deduced from these studies appears very close to the one in the bulk α phase of CuPc. The work function of the films was found to be decreasing during the growth and was correlated with the molecular orientation.

  1. Spectroscopic and structural investigation of interaction product of 8-mercaptoquinoline with molecular iodine

    NASA Astrophysics Data System (ADS)

    Chernov'yants, Margarita S.; Starikova, Zoya A.; Karginova, Anastasia O.; Kolesnikova, Tatiana S.; Tereznikov, Alexander Yu.

    2013-11-01

    The behavior of 8-mercaptoquinoline, which is a potential antithyroid drug toward molecular iodine was investigated. The ability of 8-mercaptoquinoline to form the outer-sphere charge-transfer complex C9H7NS·I2 with iodine molecular in dilute chloroform solution has been studied by UV/vis spectroscopy (lg β = 3.14). The crystal structure of the new salt 8-(quinoline-8-yldisulfonyl)quinolinium triiodide - product of irreversible oxidation of 8-mercaptoquinoline was determined by X-ray diffraction. Intramolecular hydrogen bond of N-H⋯N type is presented in the organic cation. The triiodide ion is the nearly centrosymmetrical anion. The 8-(quinoline-8-yldisulfanyl)quinolinium cations form dimers through π-π-stacking interaction between quinolinium rings. The reduced intramolecular interactions are observed between iodine - sulfur atoms and iodine-hydrogen atoms with shortened contacts (less of sum of van-der-waals contacts).

  2. Coupling lattice Boltzmann and molecular dynamics models for dense fluids

    NASA Astrophysics Data System (ADS)

    Dupuis, A.; Kotsalis, E. M.; Koumoutsakos, P.

    2007-04-01

    We propose a hybrid model, coupling lattice Boltzmann (LB) and molecular dynamics (MD) models, for the simulation of dense fluids. Time and length scales are decoupled by using an iterative Schwarz domain decomposition algorithm. The MD and LB formulations communicate via the exchange of velocities and velocity gradients at the interface. We validate the present LB-MD model in simulations of two- and three-dimensional flows of liquid argon past and through a carbon nanotube. Comparisons with existing hybrid algorithms and with reference MD solutions demonstrate the validity of the present approach.

  3. Coupling lattice Boltzmann and molecular dynamics models for dense fluids.

    PubMed

    Dupuis, A; Kotsalis, E M; Koumoutsakos, P

    2007-04-01

    We propose a hybrid model, coupling lattice Boltzmann (LB) and molecular dynamics (MD) models, for the simulation of dense fluids. Time and length scales are decoupled by using an iterative Schwarz domain decomposition algorithm. The MD and LB formulations communicate via the exchange of velocities and velocity gradients at the interface. We validate the present LB-MD model in simulations of two- and three-dimensional flows of liquid argon past and through a carbon nanotube. Comparisons with existing hybrid algorithms and with reference MD solutions demonstrate the validity of the present approach.

  4. Modeling of Switching and Hysteresis in Molecular Transport

    NASA Technical Reports Server (NTRS)

    Samanta, Manoj P.; Partridge, Harry (Technical Monitor)

    2002-01-01

    The conventional way of modeling current transport in two and three terminal molecular devices could be inadequate for certain cases involving switching and hysteresis. Here we present an alternate approach. Contrary to the regular way where applied bias directly modulates the conducting energy levels of the molecule, our method introduces a nonlinear potential energy surface varying with the applied bias as a control parameter. A time-dynamics is also introduced properly accounting for switching and hysteresis behavior. Although the model is phenomenological at this stage, we believe any detailed model would contain similar descriptions at its core.

  5. A new molecular thermodynamic model for multicomponent Ising lattice

    NASA Astrophysics Data System (ADS)

    Yang, Jianyong; Xin, Qin; Sun, Lei; Liu, Honglai; Hu, Ying; Jiang, Jianwen

    2006-10-01

    A new molecular thermodynamic model is developed for multicomponent Ising lattice based on a generalized nonrandom factor from binary system. Predictions of the nonrandom factor and the internal energy of mixing for ternary and quaternary systems match accurately with simulation results. Predictions of liquid-liquid phase equilibrium for ternary systems are in nearly perfect agreement with simulation results, and substantially improved from Flory-Huggins theory and the lattice-cluster theory. The model also satisfactorily correlates the experimental data of real ternary systems. The concise expression and the accuracy of the new model make it well suited for practical engineering applications.

  6. Molecular Code Division Multiple Access: Gaussian Mixture Modeling

    NASA Astrophysics Data System (ADS)

    Zamiri-Jafarian, Yeganeh

    Communications between nano-devices is an emerging research field in nanotechnology. Molecular Communication (MC), which is a bio-inspired paradigm, is a promising technique for communication in nano-network. In MC, molecules are administered to exchange information among nano-devices. Due to the nature of molecular signals, traditional communication methods can't be directly applied to the MC framework. The objective of this thesis is to present novel diffusion-based MC methods when multi nano-devices communicate with each other in the same environment. A new channel model and detection technique, along with a molecular-based access method, are proposed in here for communication between asynchronous users. In this work, the received molecular signal is modeled as a Gaussian mixture distribution when the MC system undergoes Brownian noise and inter-symbol interference (ISI). This novel approach demonstrates a suitable modeling for diffusion-based MC system. Using the proposed Gaussian mixture model, a simple receiver is designed by minimizing the error probability. To determine an optimum detection threshold, an iterative algorithm is derived which minimizes a linear approximation of the error probability function. Also, a memory-based receiver is proposed to improve the performance of the MC system by considering previously detected symbols in obtaining the threshold value. Numerical evaluations reveal that theoretical analysis of the bit error rate (BER) performance based on the Gaussian mixture model match simulation results very closely. Furthermore, in this thesis, molecular code division multiple access (MCDMA) is proposed to overcome the inter-user interference (IUI) caused by asynchronous users communicating in a shared propagation environment. Based on the selected molecular codes, a chip detection scheme with an adaptable threshold value is developed for the MCDMA system when the proposed Gaussian mixture model is considered. Results indicate that the

  7. Molecular dynamics modeling of a nanomaterials-water surface interaction

    NASA Astrophysics Data System (ADS)

    Nejat Pishkenari, Hossein; Keramati, Ramtin; Abdi, Ahmad; Minary-Jolandan, Majid

    2016-04-01

    In this article, we study the formation of nanomeniscus around a nanoneedle using molecular dynamics simulation approach. The results reveal three distinct phases in the time-evolution of meniscus before equilibrium according to the contact angle, meniscus height, and potential energy. In addition, we investigated the correlation between the nanoneedle diameter and nanomeniscus characteristics. The results have applications in various fields such as scanning probe microscopy and rheological measurements.

  8. In Silico Modeling of the Immune System: Cellular and Molecular Scale Approaches

    PubMed Central

    Belfiore, Mariagrazia; Aricò, Giuseppina; Ronsisvalle, Simone

    2014-01-01

    The revolutions in biotechnology and information technology have produced clinical data, which complement biological data. These data enable detailed descriptions of various healthy and diseased states and responses to therapies. For the investigation of the physiology and pathology of the immune responses, computer and mathematical models have been used in the last decades, enabling the representation of biological processes. In this modeling effort, a major issue is represented by the communication between models that work at cellular and molecular level, that is, multiscale representation. Here we sketch some attempts to model immune system dynamics at both levels. PMID:24804217

  9. In silico modeling of the immune system: cellular and molecular scale approaches.

    PubMed

    Belfiore, Mariagrazia; Pennisi, Marzio; Aricò, Giuseppina; Ronsisvalle, Simone; Pappalardo, Francesco

    2014-01-01

    The revolutions in biotechnology and information technology have produced clinical data, which complement biological data. These data enable detailed descriptions of various healthy and diseased states and responses to therapies. For the investigation of the physiology and pathology of the immune responses, computer and mathematical models have been used in the last decades, enabling the representation of biological processes. In this modeling effort, a major issue is represented by the communication between models that work at cellular and molecular level, that is, multiscale representation. Here we sketch some attempts to model immune system dynamics at both levels.

  10. Computational models of molecular self-organization in cellular environments.

    PubMed

    LeDuc, Philip; Schwartz, Russell

    2007-01-01

    The cellular environment creates numerous obstacles to efficient chemistry, as molecular components must navigate through a complex, densely crowded, heterogeneous, and constantly changing landscape in order to function at the appropriate times and places. Such obstacles are especially challenging to self-organizing or self-assembling molecular systems, which often need to build large structures in confined environments and typically have high-order kinetics that should make them exquisitely sensitive to concentration gradients, stochastic noise, and other non-ideal reaction conditions. Yet cells nonetheless manage to maintain a finely tuned network of countless molecular assemblies constantly forming and dissolving with a robustness and efficiency generally beyond what human engineers currently can achieve under even carefully controlled conditions. Significant advances in high-throughput biochemistry and genetics have made it possible to identify many of the components and interactions of this network, but its scale and complexity will likely make it impossible to understand at a global, systems level without predictive computational models. It is thus necessary to develop a clear understanding of how the reality of cellular biochemistry differs from the ideal models classically assumed by simulation approaches and how simulation methods can be adapted to accurately reflect biochemistry in the cell, particularly for the self-organizing systems that are most sensitive to these factors. In this review, we present approaches that have been undertaken from the modeling perspective to address various ways in which self-organization in the cell differs from idealized models.

  11. The activation strain model and molecular orbital theory

    PubMed Central

    Wolters, Lando P; Bickelhaupt, F Matthias

    2015-01-01

    The activation strain model is a powerful tool for understanding reactivity, or inertness, of molecular species. This is done by relating the relative energy of a molecular complex along the reaction energy profile to the structural rigidity of the reactants and the strength of their mutual interactions: ΔE(ζ) = ΔEstrain(ζ) + ΔEint(ζ). We provide a detailed discussion of the model, and elaborate on its strong connection with molecular orbital theory. Using these approaches, a causal relationship is revealed between the properties of the reactants and their reactivity, e.g., reaction barriers and plausible reaction mechanisms. This methodology may reveal intriguing parallels between completely different types of chemical transformations. Thus, the activation strain model constitutes a unifying framework that furthers the development of cross-disciplinary concepts throughout various fields of chemistry. We illustrate the activation strain model in action with selected examples from literature. These examples demonstrate how the methodology is applied to different research questions, how results are interpreted, and how insights into one chemical phenomenon can lead to an improved understanding of another, seemingly completely different chemical process. WIREs Comput Mol Sci 2015, 5:324–343. doi: 10.1002/wcms.1221 PMID:26753009

  12. Computational Protocol for Modeling Thermochromic Molecular Crystals: Salicylidene Aniline As a Case Study.

    PubMed

    Presti, Davide; Labat, Fréderic; Pedone, Alfonso; Frisch, Michael J; Hratchian, Hrant P; Ciofini, Ilaria; Menziani, Maria Cristina; Adamo, Carlo

    2014-12-09

    A computational protocol that combines periodic and QM/QM' calculations has been applied to investigate the structural (geometrical and electronic) and photophysical absorption properties of the salicylidene aniline (SA) thermochromic molecular crystal. The protocol consists of three different steps, namely (i) the description of the molecular crystal using a periodic approach taking into account dispersion interactions, (ii) the identification of reliable finite models (clusters), and (iii) the calculation of vertical transition energies including environmental effects through the use of an electronic embedding model (QM/QM' ONIOM approach). The encouraging results obtained in this work for the β polymorph of SA, both in terms of accuracy and computational cost, open the way to the simulation and the prediction of the photophysical behavior of other molecular crystals, especially those much less well characterized experimentally.

  13. Multiscale modelling of transport in clays from the molecular to the sample scale

    NASA Astrophysics Data System (ADS)

    Rotenberg, Benjamin; Marry, Virginie; Salanne, Mathieu; Jardat, Marie; Turq, Pierre

    2014-11-01

    We report some recent applications of multiscale modelling to the transport of ions, water and CO2 in clays. On the one hand, simulations on different scales allow us to investigate the physicochemical processes underlying the geochemical and transport behaviour of these fluids in the interparticle pores and at the surface of clay minerals. We discuss more specifically the insights gained from molecular simulations into the acidity of surface edge sites, ion exchange and the behaviour of clay interlayers in contact with a CO2 reservoir. On the other hand, upscaling the descriptions from the molecular level to the macroscopic scale without forgetting the fundamental role of interfaces on the mesoscopic scale provides a means to capture complex phenomena such as electrokinetic couplings. We illustrate the complementarity of molecular dynamics, lattice-based mesoscopic simulations and Pore Network Models to address this issue.

  14. Molecular modeling of sigma 1 receptor ligands: a model of binding conformational and electrostatic considerations.

    PubMed

    Gund, Tamara M; Floyd, Jie; Jung, Dawoon

    2004-01-01

    We have performed molecular modeling studies on several sigma 1 specific ligands, including PD144418, spipethiane, haloperidol, pentazocine, and others to develop a pharmacophore for sigma 1 receptor-ligand binding, under the assumption that all the compounds interact at the same receptor binding site. The modeling studies have investigated the conformational and electrostatic properties of the ligands. Superposition of active molecules gave the coordinates of the hypothetical 5-point sigma 1 pharmacophore, as follows: R1 (0.85, 7.26, 0.30); R2 (5.47, 2.40, -1.51); R3 (-2.57, 4.82, -7.10); N (-0.71, 3.29, -6.40); carbon centroid (3.16, 4.83, -0.60), where R1, R2 were constructed onto the aromatic ring of each compound to represent hydrophobic interactions with the receptor; and R3 represents a hydrogen bond between the nitrogen atom and the receptor. Additional analyses were used to describe secondary binding sites to electronegative groups such as oxygen or sulfur atom. Those coordinates are (2.34, 5.08, -4.18). The model was verified by fitting other sigma 1 receptor ligands. This model may be used to search conformational databases for other possibly active ligands. In conjunction with rational drug design techniques the model may be useful in design and synthesis of novel sigma 1 ligands of high selectivity and potency. Calculations were performed using Sybyl 6.5.

  15. Assessing High School Chemistry Students' Modeling Sub-Skills in a Computerized Molecular Modeling Learning Environment

    ERIC Educational Resources Information Center

    Dori, Yehudit Judy; Kaberman, Zvia

    2012-01-01

    Much knowledge in chemistry exists at a molecular level, inaccessible to direct perception. Chemistry instruction should therefore include multiple visual representations, such as molecular models and symbols. This study describes the implementation and assessment of a learning unit designed for 12th grade chemistry honors students. The organic…

  16. Nitrogen Substituted Phenothiazine Derivatives: Modelling of Molecular Self-Assembling

    PubMed Central

    Bende, Attila; Turcu, Ioan

    2011-01-01

    The study aims to present a detailed theoretical investigation of noncovalent intermolecular interactions between different π–π stacking nitrogen substituted phenothiazine derivatives by applying second-order Møller-Plesset perturbation (MP2), density functional (DFT) and semiempirical theories. The conformational stability of these molecular systems is mainly given by the dispersion-type electron correlation effects. The density functional tight-binding (DFTB) method applied for dimer structures are compared with the results obtained by the higher level theoretical methods. Additionally, the optimal configuration of the investigated supramolecular systems and their self-assembling properties are discussed. PMID:21686172

  17. The Role of Molecular Modeling in TiO₂ Photocatalysis.

    PubMed

    Cinar, Zekiye

    2017-03-30

    Molecular Modeling methods play a very important role in TiO₂ photocatalysis. Recent advances in TiO₂ photocatalysis have produced a number of interesting surface phenomena, reaction products, and various novel visible light active photocatalysts with improved properties. Quantum mechanical calculations appear promising as a means of describing the mechanisms and the product distributions of the photocatalytic degradation reactions of organic pollutants in both gas and aqueous phases. Since quantum mechanical methods utilize the principles of particle physics, their use may be extended to the design of new photocatalysts. This review introduces molecular modeling methods briefly and emphasizes the use of these methods in TiO₂ photocatalysis. The methods used for obtaining information about the degradabilities of the pollutant molecules, predicting reaction mechanisms, and evaluating the roles of the dopants and surface modifiers are explained.

  18. Theoretical study on electromagnetically induced transparency in molecular aggregate models using quantum Liouville equation method

    SciTech Connect

    Minami, Takuya; Nakano, Masayoshi

    2015-01-22

    Electromagnetically induced transparency (EIT), which is known as an efficient control method of optical absorption property, is investigated using the polarizability spectra and population dynamics obtained by solving the quantum Liouville equation. In order to clarify the intermolecular interaction effect on EIT, we examine several molecular aggregate models composed of three-state monomers with the dipole-dipole coupling. On the basis of the present results, we discuss the applicability of EIT in molecular aggregate systems to a new type of optical switch.

  19. "Zwitterionic Proton Sponge" Hydrogen Bonding Investigations on the Basis of Car-Parrinello Molecular Dynamics.

    PubMed

    Jezierska, Aneta; Panek, Jarosław J

    2015-06-22

    1,8-Bis(dimethylamino)-4,5-dihydroxynaphthalene has been investigated on the basis of static DFT computations and Car-Parrinello molecular dynamics. The simulations were performed in the gas phase and in the solid state. The studied "zwitterionic proton sponge" possesses two, short intramolecular hydrogen bonds (O-H···O and N-H···N) classified as Low Barrier Hydrogen Bonds (LBHBs); therefore, the system studied is strongly anharmonic. In addition, the compound exists as a "zwitterion" in solution and in the solid state, thus the intramolecular hydrogen bonds belong to the class of charge-assisted interactions. The applied quantum-chemical methods enabled investigations of metric and spectroscopic parameters of the molecule. The time-evolution investigations of the H-bonding showed a strong delocalization of the bridge protons and their high mobility, reflected in the low barriers on the free energy surfaces. Frequent proton transfer phenomena were noticed. The power spectra of atomic velocity were computed to analyze the vibrational features associated with O-H and N-H stretching. A broad absorption was indicated for both hydrogen bridges. For the first time, Car-Parrinello molecular dynamics results are reported for the compound, and they indicate a broad, shallow but not barrierless, potential well for each of the bridge protons.

  20. Optimal conditions for mycelial growth of Schizosaccharomyces japonicus cells in liquid medium: it enables the molecular investigation of dimorphism.

    PubMed

    Papp, László; Sipiczki, Matthias; Holb, Imre J; Miklós, Ida

    2014-12-01

    The non-pathogenic dimorphic fission yeast, Schizosaccharomyces japonicus, could be a suitable model organism for investigation of the genetic background of mycelial growth, as it has a haploid chromosome set and its genome is sequenced. Since earlier results have suggested that its morphological transition required solid substrates, but molecular biological experiments would require hyphae production in a liquid medium, we wanted to find circumstances which would enable hyphae production in liquid media. Several external conditions were investigated, but the strongest inducer was fetal bovine serum (FBS). Its positive effect could be hampered by heat and was dependent on pH, temperature and concentration of the serum. Other protein-containing compounds, such as peptone and bovine serum albumin or amino acids, proved to be ineffective or weak. Generally, the uninduced and induced mycelial growth of Sz. japonicus could be improved by lower external pH and higher temperature.

  1. Modeling large RNAs and ribonucleoprotein particles using molecular mechanics techniques.

    PubMed Central

    Malhotra, A; Tan, R K; Harvey, S C

    1994-01-01

    There is a growing body of low-resolution structural data that can be utilized to devise structural models for large RNAs and ribonucleoproteins. These models are routinely built manually. We introduce an automated refinement protocol to utilize such data for building low-resolution three-dimensional models using the tools of molecular mechanics. In addition to specifying the positions of each nucleotide, the protocol provides quantitative estimates of the uncertainties in those positions, i.e., the resolution of the model. In typical applications, the resolution of the models is about 10-20 A. Our method uses reduced representations and allows us to refine three-dimensional structures of systems as big as the 16S and 23S ribosomal RNAs, which are about one to two orders of magnitude larger than nucleic acids that can be examined by traditional all-atom modeling methods. Nonatomic resolution structural data--secondary structure, chemical cross-links, chemical and enzymatic footprinting patterns, protein positions, solvent accessibility, and so on--are combined with known motifs in RNA structure to predict low-resolution models of large RNAs. These structural constraints are imposed on the RNA chain using molecular mechanics-type potential functions with parameters based on the quality of experimental data. Surface potential functions are used to incorporate shape and positional data from electron microscopy image reconstruction experiments into our models. The structures are optimized using techniques of energy refinement to get RNA folding patterns. In addition to providing a consensus model, the method finds the range of models consistent with the data, which allows quantitative evaluation of the resolution of the model. The method also identifies conflicts in the experimental data. Although our protocol is aimed at much larger RNAs, we illustrate these techniques using the tRNA structure as an example and test-bed. Images FIGURE 7 FIGURE 8 PMID:7521223

  2. Modeling molecular hydrogen emission in M dwarf exoplanetary systems

    NASA Astrophysics Data System (ADS)

    Evonosky, William; France, Kevin; Kruczek, Nick E.; Youngblood, Allison; Measurements of the Ultraviolet Spectral Characteristics of Low-mass Exoplanet host Stars (MUSCLES)

    2017-01-01

    Exoplanets orbiting low-mass stars are prime candidates for atmospheric characterization due to their astronomical abundance and short orbital periods. These planets orbit stars that are often more active than main sequence solar-type stars. They are exposed to differing levels of ultraviolet radiation which can cause traditional “biosignature” gases to be generated abiotically, potentially causing false-positive identifications of life. We modeled the recently discovered molecular hydrogen emission in the ultraviolet spectra (1350 - 1650 Å) as arising from the stellar surface, excited by radiation generated in the upper chromosphere. The model was compared with observed hydrogen emission from the “Measurements of the Ultraviolet Spectral Characteristics of Low-mass Exoplanet host Stars” (MUSCLES) survey by conducting a grid search and implementing a chi-squared minimization routine. We considered only progressions from the [1, 4] and [1, 7] first excited electronic levels. Our modeling procedure varied the atomic hydrogen column density (in the chromosphere) as well as the photospheric molecular hydrogen column density and temperature. The model required as an input a reconstructed intrinsic Lyman α profile which served as the pumping radiation for the molecular hydrogen. We found that an atomic hydrogen column density of log10N(H I) = 14.13 ± 0.16 cm-2 represents a breaking point above which there is not enough Lyman α flux available to excite a significant molecular hydrogen population into the [1, 7] state. We also present H2 temperatures which may suggest that star spots on low mass stars persist longer, and encompass more area than star spots on solar-type stars.

  3. Kinetic modelling of molecular hydrogen transport in microporous carbon materials.

    SciTech Connect

    Hankel, M.; Zhang, H.; Nguyen, T. X.; Bhatia, S. K.; Gray, S. K.; Smith, S. C.

    2011-01-01

    The proposal of kinetic molecular sieving of hydrogen isotopes is explored by employing statistical rate theory methods to describe the kinetics of molecular hydrogen transport in model microporous carbon structures. A Lennard-Jones atom-atom interaction potential is utilized for the description of the interactions between H{sub 2}/D{sub 2} and the carbon framework, while the requisite partition functions describing the thermal flux of molecules through the transition state are calculated quantum mechanically in view of the low temperatures involved in the proposed kinetic molecular sieving application. Predicted kinetic isotope effects for initial passage from the gas phase into the first pore mouth are consistent with expectations from previous modeling studies, namely, that at sufficiently low temperatures and for sufficiently narrow pore mouths D{sub 2} transport is dramatically favored over H{sub 2}. However, in contrast to expectations from previous modeling, the absence of any potential barrier along the minimum energy pathway from the gas phase into the first pore mouth yields a negative temperature dependence in the predicted absolute rate coefficients - implying a negative activation energy. In pursuit of the effective activation barrier, we find that the minimum potential in the cavity is significantly higher than in the pore mouth for nanotube-shaped models, throwing into question the common assumption that passage through the pore mouths should be the rate-determining step. Our results suggest a new mechanism that, depending on the size and shape of the cavity, the thermal activation barrier may lie in the cavity rather than at the pore mouth. As a consequence, design strategies for achieving quantum-mediated kinetic molecular sieving of H{sub 2}/D{sub 2} in a microporous membrane will need, at the very least, to take careful account of cavity shape and size in addition to pore-mouth size in order to ensure that the selective step, namely passage

  4. Tools for Modeling & Simulation of Molecular and Nanoelectronics Devices

    DTIC Science & Technology

    2012-06-14

    1) Tools for Modeling & Simulation of Molecular and Nanoelectronics Devices 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...parallel algorithms to allow for simulations of realistic device structures. In Phase II, these methods will be developed and will be integrated into...the integration of other simulation engines into the ATK package. This allows these codes, which are all of academic origin to date, to be driven from

  5. Investigating the Interaction Pattern and Structural Elements of a Drug-Polymer Complex at the Molecular Level.

    PubMed

    Nie, Haichen; Mo, Huaping; Zhang, Mingtao; Song, Yang; Fang, Ke; Taylor, Lynne S; Li, Tonglei; Byrn, Stephen R

    2015-07-06

    Strong associations between drug and polymeric carriers are expected to contribute to higher drug loading capacities and better physical stability of amorphous solid dispersions. However, molecular details of the interaction patterns and underlying mechanisms are still unclear. In the present study, a series of amorphous solid dispersions of clofazimine (CLF), an antileprosy drug, were prepared with different polymers by applying the solvent evaporation method. When using hypromellose phthalate (HPMCP) as the carrier, the amorphous solid dispersion system exhibits not only superior drug loading capacity (63% w/w) but also color change due to strong drug-polymer association. In order to further explain these experimental observations, the interaction between CLF and HPMCP was investigated in a nonpolar volatile solvent system (chloroform) prior to forming the solid dispersion. We observed significant UV/vis and (1)H NMR spectral changes suggesting the protonation of CLF and formation of ion pairs between CLF and HPMCP in chloroform. Furthermore, nuclear Overhauser effect spectroscopy (NOESY) and diffusion order spectroscopy (DOSY) were employed to evaluate the strength of associations between drug and polymers, as well as the molecular mobility of CLF. Finally, by correlating the experimental values with quantum chemistry calculations, we demonstrate that the protonated CLF is binding to the carboxylate group of HPMCP as an ion pair and propose a possible structural model of the drug-polymer complex. Understanding the drug and carrier interaction patterns from a molecular perspective is critical for the rational design of new amorphous solid dispersions.

  6. Transcriptomic and metabolomic approaches to investigate the molecular responses of human cell lines exposed to the flame retardant hexabromocyclododecane (HBCD).

    PubMed

    Zhang, Jinkang; Williams, Timothy D; Abdallah, Mohamed Abou-Elwafa; Harrad, Stuart; Chipman, James K; Viant, Mark R

    2015-12-01

    The potential for human exposure to the brominated flame retardant, hexabromocyclododecane (HBCD) has given rise to health concerns, yet there is relatively limited knowledge about its possible toxic effects and the underlying molecular mechanisms that may mediate any impacts on health. In this study, unbiased transcriptomic and metabolomic approaches were employed to investigate the potential molecular changes that could lead to the toxicity of HBCD under concentrations relevant to human exposure conditions using in vitro models. A concentration-dependent cytotoxic effect of HBCD to A549 and HepG2/C3A cells was observed based on MTT assays or CCK-8 assays with EC50 values of 27.4 μM and 63.0 μM, respectively. Microarray-based transcriptomics and mass spectrometry-based metabolomics revealed few molecular changes in A549 cells or HepG2/C3A cells following a 24-hour exposure to several sub-lethal concentrations (2 to 4000 nM) of HBCD. Quantification of the level of HBCD in the HepG2/C3A exposed cells suggested that the flame retardant was present at concentrations several orders of magnitude higher than those reported to occur in human tissues. We conclude that at the concentrations known to be achievable following exposure in humans, HBCD exhibits no detectable acute toxicity in A549 cells, representative of the lung, or in HepG2/C3A cells, that are hepatocytes with some xenobiotic metabolic capacity.

  7. Mechanism of diffusive transport in molecular spider models

    NASA Astrophysics Data System (ADS)

    Semenov, Oleg; Olah, Mark J.; Stefanovic, Darko

    2011-02-01

    Recent advances in single-molecule chemistry have led to designs for artificial multipedal walkers that follow tracks of chemicals. We investigate the motion of a class of walkers, called molecular spiders, which consist of a rigid chemically inert body and several flexible enzymatic legs. The legs can reversibly bind to chemical substrates on a surface and through their enzymatic action convert them to products. The legs can also reversibly bind to products, but at a different rate. Antal and Krapivsky have proposed a model for molecular spider motion over regular one-dimensional lattices [T. Antal and P. L. Krapivsky, Phys. Rev. ENATUAS1539-375510.1103/PhysRevE.76.021121 76, 021121 (2007).]. In the model the legs hop from site to site under constraints imposed by connection to a common body. The first time a leg visits a site, the site is an uncleaved substrate, and the leg hops from this site only once it has cleaved it into a product. This cleavage happens at a rate r<1, slower than dissociation from a product site, r=1. The effect of cleavage is to slow down the hopping rate for legs that visit a site for the first time. Along with the constraints imposed on the legs, this leads to an effective bias in the direction of unvisited sites that decreases the average time needed to visit n sites. The overall motion, however, remains diffusive in the long time limit. We have reformulated the Antal-Krapivsky model as a continuous-time Markov process and simulated many traces of this process using kinetic Monte Carlo techniques. Our simulations show a previously unpredicted transient behavior wherein spiders with small r values move superdiffusively over significant distances and times. We explain this transient period of superdiffusive behavior by describing the spider process as switching between two metastates: a diffusive state D wherein the spider moves in an unbiased manner over previously visited sites, and a boundary state B wherein the spider is on the

  8. Investigations of the Formation of Molecular Hydrogen on Dust Grain Analogues

    NASA Technical Reports Server (NTRS)

    Vidali, Gianfranco; Roser, Joseph E.; Manico, Giulio; Pirronello, Valerio

    2002-01-01

    In the last four years we have been working to investigate the formation of molecular hydrogen on surfaces of materials of astrophysical interest, such as silicates, carbonaceous particles and ices, and in conditions approximating the ones present in a variety of astrophysical environments. Our experimental studies - the first of their kind and complemented with computer simulations and theoretical analyses - have given not only hydrogen recombination rates under different ISM conditions, but they have also offered new insights into this fundamental astrophysical problem. Here we summarize our experimental methods and most significant results.

  9. Application of molecular simulation to investigate chrome(III)-crosslinked collagen problems

    NASA Astrophysics Data System (ADS)

    Ding, Yun-Qiao; Chen, Cheng-Lung; Gu, Qi-Rui; Liao, Jun-Min; Chuang, Po-Hsiang

    2014-04-01

    Molecular dynamics simulation with a modified CHARMM (Chemistry at Harvard Macromolecular Mechanics) force field was carried out to investigate the properties of chrome-tanned collagen in comparison with chrome-free collagen under hydrated and dehydrated conditions. An attempt has been made to explain the microcosmic origins of the various properties of the chromium(III)-crosslinked collagen. The present simulation describes the clear crosslinking topology of polychromiums to peptide chains, identifies the linking site and the capacity of the linkage, explains why the efficiency is not 100% in a practical tanning process and provides a new viewpoint on the crosslinking of the polychromium with the side chains of the collagen.

  10. Investigations to improve carbon dioxide control with amine and molecular sieve type sorbers

    NASA Technical Reports Server (NTRS)

    Bertrand, J. F.; Brose, H. F.; Kester, F. L.; Lunde, P. J.

    1972-01-01

    The optimization trends and operating parameters of an integral molecular sieve bed heat exchanger were investigated. The optimum combination of substrate and coating for the HS-B porous polymer was determined based on the CO2 dynamic capacity in the presence of water vapor. Full size HS-B canister performance was evaluated. An Amine CO2 Concentrator utilizing IR-45 sorber material and available Manned Orbiting Laboratory hardware was designed, fabricated and tested for use as an experiment in the NASA 90-day space simulator test of 1970. It supported four men in the simulator for 71 days out of the 90-day test duration.

  11. Virtual-Wall Model for Molecular Dynamics Simulation.

    PubMed

    Qian, Lijuan; Tu, Chengxu; Bao, Fubing; Zhang, Yonghao

    2016-12-09

    A large number of molecules are usually required to model atomic walls in molecular dynamics simulations. A virtual-wall model is proposed in this study to describe fluid-wall molecular interactions, for reducing the computational time. The infinite repetition of unit cell structures within the atomic wall causes the periodicity of the force acting on a fluid molecule from the wall molecules. This force is first calculated and then stored in the memory. A fluid molecule appearing in the wall force field is subjected to the force from the wall molecules. The force can then be determined by the position of the molecule relative to the wall. This model avoids excessive calculations of fluid-wall interactions and reduces the computational time drastically. The time reduction is significant for small fluid density and channel height. The virtual-wall model is applied to Poiseuille and Couette flows, and to a flow in a channel with a rough surface. Results of the virtual and atomic wall simulations agree well with each other, thereby indicating the usefulness of the virtual-wall model. The appropriate bin size and cut-off radius in the virtual-wall model are also discussed.

  12. Investigation of mechanical strength of 2D nanoscale structures using a molecular dynamics based computational intelligence approach

    NASA Astrophysics Data System (ADS)

    Garg, A.; Vijayaraghavan, V.; Wong, C. H.; Tai, K.; Singru, Pravin M.; Mahapatra, S. S.; Sangwan, K. S.

    2015-09-01

    A molecular dynamics (MD) based computational intelligence (CI) approach is proposed to investigate the Young modulus of two graphene sheets: Armchair and Zigzag. In this approach, the effect of aspect ratio, the temperature, the number of atomic planes and the vacancy defects on the Young modulus of two graphene sheets are first analyzed using the MD simulation. The data obtained using the MD simulation is then fed into the paradigm of a CI cluster comprising of genetic programming, which was specifically designed to formulate the explicit relationship of Young modulus of two graphene structures. We find that the MD-based-CI model is able to model the Young modulus of two graphene structures very well, which compiles in good agreement with that of experimental results obtained from the literature. Additionally, we also conducted sensitivity and parametric analysis and found that the number of defects has the most dominating influence on the Young modulus of two graphene structures.

  13. Model of self assembled monolayer based molecular diodes made of ferrocenyl-alkanethiols

    NASA Astrophysics Data System (ADS)

    Duche, David; Planchoke, Ujwol; Dang, Florian-Xuan; Le Rouzo, Judikael; Bescond, Marc; Simon, Jean-Jacques; Balaban, Teodor Silviu; Escoubas, Ludovic

    2017-03-01

    There has been significant work investigating the use of self assembled monolayers (SAMs) made of ferrocenyl terminated alkanethiols for realizing molecular diodes, leading to remarkably large forward-to-reverse current rectification ratios. In this study, we use a multiband barrier tunneling model to examine the electrical properties of SAM-based molecular diodes made of HSC9Fc, HSC11Fc, and HSCiFcC13-i (0 ≤ i ≤ 13). Using our simple physical model, we reproduce the experimental data of charge transport across various ferrocenyl substituted alkanethiols performed by Nijhuis, Reus, and Whitesides [J. Am. Chem. Soc. 132, 18386-184016 (2010)] and Yuan et al. [Nat. Commun. 6, 6324 (2015)]. Especially, the model allows predicting the rectification direction in HSCiFcC13-i (0 ≤ i ≤ 13) based molecular diodes depending on the position of the ferrocenyl (Fc) moiety within the molecules. We show that the asymmetry of the barrier length at both sides of the Highest Occupied Molecular Orbital of the ferrocenyl moiety strongly contributes to the rectifying properties of ferrocenyl-alkanethiol based molecular junctions. Furthermore, our results reveal that bound and quasi-bound states play an important role in the charge transport.

  14. A Self-Assisting Protein Folding Model for Teaching Structural Molecular Biology.

    PubMed

    Davenport, Jodi; Pique, Michael; Getzoff, Elizabeth; Huntoon, Jon; Gardner, Adam; Olson, Arthur

    2017-04-04

    Structural molecular biology is now becoming part of high school science curriculum thus posing a challenge for teachers who need to convey three-dimensional (3D) structures with conventional text and pictures. In many cases even interactive computer graphics does not go far enough to address these challenges. We have developed a flexible model of the polypeptide backbone using 3D printing technology. With this model we have produced a polypeptide assembly kit to create an idealized model of the Triosephosphate isomerase mutase enzyme (TIM), which forms a structure known as TIM barrel. This kit has been used in a laboratory practical where students perform a step-by-step investigation into the nature of protein folding, starting with the handedness of amino acids to the formation of secondary and tertiary structure. Based on the classroom evidence we collected, we conclude that these models are valuable and inexpensive resource for teaching structural molecular biology.

  15. Investigation of the torsional barrier of EDOT using molecular mechanics and DFT methods.

    PubMed

    Durães, Jussara A; da Silva Filho, Demétrio A; Ceschin, Artemis M; Sales, Maria J A; Martins, João B L

    2014-08-01

    When heterocyclic monomers are polymerized by electrochemical or chemical methods, they form fully conjugated polymers which have a wide range of applications due to their outstanding electronic properties. Among this class of compounds, thiophene derivatives are widely used due to their chemical stability and synthesis flexibility. With the goal to investigate the torsion barrier of polymer chains, a few units of 3,4-ethylenedioxythiophene (EDOT) were chosen and submitted to molecular mechanics (MM), density functional theory (DFT) and coupled cluster CCSD(T) calculations. This study helps to understand the performance and transferability of force fields used in molecular mechanics and molecular dynamics simulations often used to describe structure-property relationships of those systems. Determination of inter-ring torsion angle was performed in a comparative study using both force field, DFT and CCSD(T) methods. A good agreement was noticed between MM and QC results and highlights the importance of the description of the interactions involving the oxygen atoms present in the structure of EDOT. These observations are related to the α,α-coupling that occurs between the monomer units and yields a linear polymer. DFT HOMO and LUMO orbitals were also presented. Finally, UV-vis spectra of EDOT units were obtained using several levels of theory by means of time-dependent DFT calculations (TD-DFT).

  16. Using solvents with different molecular sizes to investigate the structure of Antheraea pernyi silk.

    PubMed

    Wang, Yu; Porter, David; Shao, Zhengzhong

    2013-11-11

    The interaction between silk and polar solvents of different molecular size can be an important tool for understanding the structural features of natural silk; in particular, the disordered regions associated with the key property of mechanical toughness. In this work, we investigate the transitions induced in the tensile performance and structure of as-reeled Antheraea pernyi silks from different silkworms by a range of solvents that can only soften the protein chains in the amorphous regions. The results indicate that polar solvents with different molecular sizes affect the silk to different degrees, and silks with slightly different structures display significantly different tensile performance in the same solvent. The solvent molecular size is quantitatively correlated with the accessible volume in the amorphous regions before and after the yield point, which suggests that the volume accessible to the solvent molecules decreases as the solvent radius increases. Moreover, silks with more ordered structure (less free volume) in the amorphous regions are less sensitive to solvents than those with more disordered structures. However, silks with higher free volume have higher toughness due to the greater strain to failure.

  17. Mechanistic modeling confronts the complexity of molecular cell biology.

    PubMed

    Phair, Robert D

    2014-11-05

    Mechanistic modeling has the potential to transform how cell biologists contend with the inescapable complexity of modern biology. I am a physiologist-electrical engineer-systems biologist who has been working at the level of cell biology for the past 24 years. This perspective aims 1) to convey why we build models, 2) to enumerate the major approaches to modeling and their philosophical differences, 3) to address some recurrent concerns raised by experimentalists, and then 4) to imagine a future in which teams of experimentalists and modelers build-and subject to exhaustive experimental tests-models covering the entire spectrum from molecular cell biology to human pathophysiology. There is, in my view, no technical obstacle to this future, but it will require some plasticity in the biological research mind-set.

  18. Two Models of Magnetic Support for Photoevaporated Molecular Clouds

    SciTech Connect

    Ryutov, D; Kane, J; Mizuta, A; Pound, M; Remington, B

    2004-05-05

    The thermal pressure inside molecular clouds is insufficient for maintaining the pressure balance at an ablation front at the cloud surface illuminated by nearby UV stars. Most probably, the required stiffness is provided by the magnetic pressure. After surveying existing models of this type, we concentrate on two of them: the model of a quasi-homogeneous magnetic field and the recently proposed model of a ''magnetostatic turbulence''. We discuss observational consequences of the two models, in particular, the structure and the strength of the magnetic field inside the cloud and in the ionized outflow. We comment on the possible role of reconnection events and their observational signatures. We mention laboratory experiments where the most significant features of the models can be tested.

  19. Investigating the binding behaviour of two avidin-based testosterone binders using molecular recognition force spectroscopy.

    PubMed

    Rangl, Martina; Leitner, Michael; Riihimäki, Tiina; Lehtonen, Soili; Hytönen, Vesa P; Gruber, Hermann J; Kulomaa, Markku; Hinterdorfer, Peter; Ebner, Andreas

    2014-02-01

    Molecular recognition force spectroscopy, a biosensing atomic force microscopy technique allows to characterise the dissociation of ligand-receptor complexes at the molecular level. Here, we used molecular recognition force spectroscopy to study the binding capability of recently developed testosterone binders. The two avidin-based proteins called sbAvd-1 and sbAvd-2 are expected to bind both testosterone and biotin but differ in their binding behaviour towards these ligands. To explore the ligand binding and dissociation energy landscape of these proteins, we tethered biotin or testosterone to the atomic force microscopy probe while the testosterone-binding protein was immobilized on the surface. Repeated formation and rupture of the ligand-receptor complex at different pulling velocities allowed determination of the loading rate dependence of the complex-rupturing force. In this way, we obtained the molecular dissociation rate (k(off)) and energy landscape distances (x(β)) of the four possible complexes: sbAvd-1-biotin, sbAvd-1-testosterone, sbAvd-2-biotin and sbAvd-2-testosterone. It was found that the kinetic off-rates for both proteins and both ligands are similar. In contrast, the x(β) values, as well as the probability of complex formations, varied considerably. In addition, competitive binding experiments with biotin and testosterone in solution differ significantly for the two testosterone-binding proteins, implying a decreased cross-reactivity of sbAvd-2. Unravelling the binding behaviour of the investigated testosterone-binding proteins is expected to improve their usability for possible sensing applications.

  20. A molecular dynamics investigation of the influence of water structure on ion conduction through a carbon nanotube.

    PubMed

    Liu, L; Patey, G N

    2017-02-21

    Molecular dynamics simulations are employed to investigate pressure-driven water and ion transport through a (9,9) carbon nanotube (CNT). We consider NaCl solutions modeled with both the TIP3P and TIP4P/2005 water models. Concentrations range from 0.25 to 2.8 mol l(-1) and temperatures from 260 to 320 K are considered. We discuss the influences on flow rates of continuum hydrodynamic considerations and molecular structural effects. We show that the flow rate of water, sodium, and chloride ions through the CNT is strongly model dependent, consistent with earlier simulations of pure water conduction. To remove the effects of different water flow rates, and clearly expose the influence of other factors on ion flow, we calculate ion transport efficiencies. Ion transport efficiencies are much smaller for TIP4P/2005 solutions than for those using the TIP3P model. Particularly at lower temperatures, the ion transport efficiencies for the TIP4P/2005 model are small, despite the fact that the nanotube conducts water at a significant rate. We trace the origin of small ion transport efficiencies to the presence of ring-like water structures within the CNT. Such structures occur commonly for the TIP4P/2005 model, but less frequently for TIP3P. The water structure acts to reduce ion "solvation" within the CNT, posing an additional barrier to ion entry and transport. Our results demonstrate that increasing the water structure within the CNT by decreasing the temperature strongly inhibits ion conduction, while still permitting significant water transport.

  1. A molecular dynamics investigation of the influence of water structure on ion conduction through a carbon nanotube

    NASA Astrophysics Data System (ADS)

    Liu, L.; Patey, G. N.

    2017-02-01

    Molecular dynamics simulations are employed to investigate pressure-driven water and ion transport through a (9,9) carbon nanotube (CNT). We consider NaCl solutions modeled with both the TIP3P and TIP4P/2005 water models. Concentrations range from 0.25 to 2.8 mol l-1 and temperatures from 260 to 320 K are considered. We discuss the influences on flow rates of continuum hydrodynamic considerations and molecular structural effects. We show that the flow rate of water, sodium, and chloride ions through the CNT is strongly model dependent, consistent with earlier simulations of pure water conduction. To remove the effects of different water flow rates, and clearly expose the influence of other factors on ion flow, we calculate ion transport efficiencies. Ion transport efficiencies are much smaller for TIP4P/2005 solutions than for those using the TIP3P model. Particularly at lower temperatures, the ion transport efficiencies for the TIP4P/2005 model are small, despite the fact that the nanotube conducts water at a significant rate. We trace the origin of small ion transport efficiencies to the presence of ring-like water structures within the CNT. Such structures occur commonly for the TIP4P/2005 model, but less frequently for TIP3P. The water structure acts to reduce ion "solvation" within the CNT, posing an additional barrier to ion entry and transport. Our results demonstrate that increasing the water structure within the CNT by decreasing the temperature strongly inhibits ion conduction, while still permitting significant water transport.

  2. Molecular Dynamics Simulations of Fracture of Model Epoxies

    SciTech Connect

    STEVENS,MARK J.

    2000-01-18

    The failure of thermosetting polymer adhesives is an important problem which particularly lacks understanding from the molecular viewpoint. While linear elastic fracture mechanics works well for such polymers far from the crack tip, the method breaks down near the crack tip where large plastic deformation occurs and the molecular details become important [1]. Results of molecular dynamics simulations of highly crosslinked polymer networks bonded to a solid surface are presented here. Epoxies are used as the guide for modeling. The focus of the simulations is the network connectivity and the interfacial strength. In a random network, the bond stress is expected to vary, and the most stressed bonds will break first [2]. Crack initiation should occur where a cluster of highly constrained bonds exists. There is no reason to expect crack initiation to occur at the interface. The results to be presented show that the solid surface limits the interfacial bonding resulting in stressed interfacial bonds and interfacial fracture. The bonds in highly-crosslinked random networks do not become stressed as expected. The sequence of molecular structural deformations that lead to failure has been determined and found to be strongly dependent upon the network connectivity. The structure of these networks and its influence on the stress-strain behavior will be discussed in general. A set of ideal, ordered networks have been constructed to manipulate the deformation sequence to achieve different fracture modes (i.e. cohesive vs. adhesive).

  3. Towards synthetic molecular motors: a model elastic-network study

    NASA Astrophysics Data System (ADS)

    Sarkar, Amartya; Flechsig, Holger; Mikhailov, Alexander S.

    2016-04-01

    Protein molecular motors play a fundamental role in biological cells and development of their synthetic counterparts is a major challenge. Here, we show how a model motor system with the operation mechanism resembling that of muscle myosin can be designed at the concept level, without addressing the implementation aspects. The model is constructed as an elastic network, similar to the coarse-grained descriptions used for real proteins. We show by numerical simulations that the designed synthetic motor can operate as a deterministic or Brownian ratchet and that there is a continuous transition between such two regimes. The motor operation under external load, approaching the stall condition, is also analysed.

  4. Role of redox centre in charge transport investigated by novel self-assembled conjugated polymer molecular junctions

    PubMed Central

    Wang, Zongrui; Dong, Huanli; Li, Tao; Hviid, Rune; Zou, Ye; Wei, Zhongming; Fu, Xiaolong; Wang, Erjing; Zhen, Yonggang; Nørgaard, Kasper; Laursen, Bo W.; Hu, Wenping

    2015-01-01

    Molecular electronics describes a field that seeks to implement electronic components made of molecular building blocks. To date, few studies have used conjugated polymers in molecular junctions despite the fact that they potentially transport charge more efficiently than the extensively investigated small-molecular systems. Here we report a novel type of molecular tunnelling junction exploring the use of conjugated polymers, which are self-assembled into ultrathin films in a distinguishable ‘planar' manner from the traditional vertically oriented small-molecule monolayers. Electrical measurements on the junctions reveal molecular-specific characteristics of the polymeric molecules in comparison with less conjugated small molecules. More significantly, we decorate redox-active functionality into polymeric backbones, demonstrating a key role of redox centre in the modulation of charge transport behaviour via energy level engineering and external stimuli, and implying the potential of employing tailor-made polymeric components as alternatives to small molecules for future molecular-scale electronics. PMID:26085081

  5. The liquid structure of tetrachloroethene: Molecular dynamics simulations and reverse Monte Carlo modeling with interatomic potentials

    NASA Astrophysics Data System (ADS)

    Gereben, Orsolya; Pusztai, László

    2013-10-01

    The liquid structure of tetrachloroethene has been investigated on the basis of measured neutron and X-ray scattering structure factors, applying molecular dynamics simulations and reverse Monte Carlo (RMC) modeling with flexible molecules and interatomic potentials. As no complete all-atom force field parameter set could be found for this planar molecule, the closest matching all-atom Optimized Potentials for Liquid Simulations (OPLS-AA) intra-molecular parameter set was improved by equilibrium bond length and angle parameters coming from electron diffraction experiments [I. L. Karle and J. Karle, J. Chem. Phys. 20, 63 (1952)]. In addition, four different intra-molecular charge distribution sets were tried, so in total, eight different molecular dynamics simulations were performed. The best parameter set was selected by calculating the mean square difference between the calculated total structure factors and the corresponding experimental data. The best parameter set proved to be the one that uses the electron diffraction based intra-molecular parameters and the charges qC = 0.1 and qCl = -0.05. The structure was further successfully refined by applying RMC computer modeling with flexible molecules that were kept together by interatomic potentials. Correlation functions concerning the orientation of molecular axes and planes were also determined. They reveal that the molecules closest to each other exclusively prefer the parallel orientation of both the molecular axes and planes. Molecules forming the first maximum of the center-center distribution have a preference for <30° and >60° axis orientation and >60° molecular plane arrangement. A second coordination sphere at ˜11 Å and a very small third one at ˜16 Å can be found as well, without preference for any axis or plane orientation.

  6. Molecular models need to be tested: the case of a solar flares discoidal HDL model.

    PubMed

    Shih, Amy Y; Sligar, Stephen G; Schulten, Klaus

    2008-06-01

    In the absence of atomic structures of high-density lipoproteins in their lipid-bound states, many molecular models have been produced based on experimental data. Using molecular dynamics, we show that a recently proposed "solar-flares" model of discoidal high-density lipoprotein is implausible. Our simulations show a collapse of the protruding solar-flare loops and a notable protein rearrangement due to an energetically unfavorable orientation of the hydrophobic protein surface toward the aqueous solvent.

  7. Single Molecule Switches and Molecular Self-Assembly: Low Temperature STM Investigations and Manipulations

    SciTech Connect

    Iancu, Violeta

    2006-08-01

    This dissertation is devoted to single molecule investigations and manipulations of two porphyrin-based molecules, chlorophyll-a and Co-popphyrin. The molecules are absorbed on metallic substrates and studied at low temperatures using a scanning tunneling microscope. The electronic, structural and mechanical properties of the molecules are investigated in detail with atomic level precision. Chlorophyll-a is the key ingredient in photosynthesis processes while Co-porphyrin is a magnetic molecule that represents the recent emerging field of molecular spintronics. Using the scanning tunneling microscope tip and the substrate as electrodes, and the molecules as active ingredients, single molecule switches made of these two molecules are demonstrated. The first switch, a multiple and reversible mechanical switch, is realized by using chlorophyll-a where the energy transfer of a single tunneling electron is used to rotate a C-C bond of the molecule's tail on a Au(111) surface. Here, the det

  8. Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

    SciTech Connect

    Bowsher, James Giles, William; Yin, Fang-Fang; Yan, Susu; Roper, Justin

    2014-01-15

    Purpose: Onboard imaging—currently performed primarily by x-ray transmission modalities—is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. Methods: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinhole SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. Results: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. Conclusions: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min

  9. Investigation of the influence factors of polyethylene molecule encapsulated into carbon nanotubes by molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Li, Qun; He, Guofang; Zhao, Rengao; Li, Yanfei

    2011-09-01

    In this work, the influence factors, namely chirality, temperature, radius and surface chemical modification, of the interaction energy for polyethylene (PE) molecule encapsulated into single-walled carbon nanotubes (SWNTs) had been investigated by molecular mechanics (MM) and molecular dynamics (MD) simulation. The results showed that all these factors would influence the interaction energy between PE and SWNTs. The interaction energy between PE molecule and the armchair SWNTs is largest among eight kinds of chiral SWNTs. The interaction energy decreases with the increase of temperature or the SWNT radius. The methyl, phenyl, hydroxyl, carboxyl, -F, and amino groups, have been introduced onto the surface of the SWNTs by the simulation software and the influence of SWNT chemical modification has also been investigated. The interaction energy between PE and chemically modified SWNTs is larger than that between PE and pristine SWNTs, and increases with increasing the concentration of the modified groups monotonously. In addition, the group electronegativity and van der Waals force will affect the interaction energy between PE and chemically modified SWNTs greatly, which can be attributed to the electronic structures of the chemically modified groups. This study can provide some useful suggestions for the composite material design and drug transport.

  10. A heterogeneous model for gas transport in carbon molecular sieves.

    PubMed

    Ding, L P; Yuan, Y X; Farooq, S; Bhatia, S K

    2005-01-18

    A dual resistance model with distribution of either barrier or pore diffusional activation energy is proposed in this work for gas transport in carbon molecular sieve (CMS) micropores. This is a novel approach in which the equilibrium is homogeneous, but the kinetics is heterogeneous. The model seems to provide a possible explanation for the concentration dependence of the thermodynamically corrected barrier and pore diffusion coefficients observed in previous studies from this laboratory on gas diffusion in CMS. The energy distribution is assumed to follow the gamma distribution function. It is shown that the energy distribution model can fully capture the behavior described by the empirical model established in earlier studies to account for the concentration dependence of thermodynamically corrected barrier and pore diffusion coefficients. A methodology is proposed for extracting energy distribution parameters, and it is further shown that the extracted energy distribution parameters can effectively predict integral uptake and column breakthrough profiles over a wide range of operating pressures.

  11. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

    PubMed Central

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  12. On the vibration of double-walled carbon nanotubes using molecular structural and cylindrical shell models

    NASA Astrophysics Data System (ADS)

    Ansari, R.; Rouhi, S.; Aryayi, M.

    2016-01-01

    The vibrational behavior of double-walled carbon nanotubes is studied by the use of the molecular structural and cylindrical shell models. The spring elements are employed to model the van der Waals interaction. The effects of different parameters such as geometry, chirality, atomic structure and end constraint on the vibration of nanotubes are investigated. Besides, the results of two aforementioned approaches are compared. It is indicated that by increasing the nanotube side length and radius, the computationally efficient cylindrical shell model gives rational results.

  13. Rio Hondo Sediment Assessment Analysis Using SAM. Numerical Model Investigation

    DTIC Science & Technology

    1991-05-01

    MISCELLANEOUS PAPER HL-91-1 M ~ RIO HONDO SEDIMENT ASSESSMENT ANALYSIS USING SAM Numerical Model Investigation AD-A238 572Ii 1 11byIll lil Nolan K...FUNDING NUMBERS Rio Hondo Sediment Assessment Analysis Using SAM; Numerical Model Investigation 6. AUTHOR(S) Nolan K. Raphelt Michael J. Trawle William A... Rio Hondo through Roswell, NM, was conducted. The investigation represented a sediment assessment level study conducted to test for potential

  14. Molecular Modeling on Berberine Derivatives toward BuChE: An Integrated Study with Quantitative Structure-Activity Relationships Models, Molecular Docking, and Molecular Dynamics Simulations.

    PubMed

    Fang, Jiansong; Pang, Xiaocong; Wu, Ping; Yan, Rong; Gao, Li; Li, Chao; Lian, Wenwen; Wang, Qi; Liu, Ai-lin; Du, Guan-hua

    2016-05-01

    A dataset of 67 berberine derivatives for the inhibition of butyrylcholinesterase (BuChE) was studied based on the combination of quantitative structure-activity relationships models, molecular docking, and molecular dynamics methods. First, a series of berberine derivatives were reported, and their inhibitory activities toward butyrylcholinesterase (BuChE) were evaluated. By 2D- quantitative structure-activity relationships studies, the best model built by partial least-square had a conventional correlation coefficient of the training set (R(2)) of 0.883, a cross-validation correlation coefficient (Qcv2) of 0.777, and a conventional correlation coefficient of the test set (Rpred2) of 0.775. The model was also confirmed by Y-randomization examination. In addition, the molecular docking and molecular dynamics simulation were performed to better elucidate the inhibitory mechanism of three typical berberine derivatives (berberine, C2, and C55) toward BuChE. The predicted binding free energy results were consistent with the experimental data and showed that the van der Waals energy term (ΔEvdw) difference played the most important role in differentiating the activity among the three inhibitors (berberine, C2, and C55). The developed quantitative structure-activity relationships models provide details on the fine relationship linking structure and activity and offer clues for structural modifications, and the molecular simulation helps to understand the inhibitory mechanism of the three typical inhibitors. In conclusion, the results of this study provide useful clues for new drug design and discovery of BuChE inhibitors from berberine derivatives.

  15. [Molecular interactions in dilute supercritical mixtures: Molecular dynamics investigation]. Final technical report, December 1, 1990--August 31, 1993

    SciTech Connect

    Debenedetti, P.G.

    1993-12-31

    Research was done in the following areas: computational and theoretical studies of molecular interactions in supercritical mixtures; supercooled liquids, network fluids, and glasses; and fast algorithms for simulating large systems on a vector processor.

  16. Investigations on the antiretroviral activity of carbon nanotubes using computational molecular approach.

    PubMed

    Krishnaraj, R Navanietha; Chandran, Saravanan; Pal, Parimal; Berchmans, Sheela

    2014-01-01

    Carbon nanotubes are the interesting class of materials with wide range of applications. They have excellent physical, chemical and electrical properties. Numerous reports were made on the antiviral activities of carbon nanotubes. However the mechanism of antiviral action is still in infancy. Herein we report, our recent novel findings on the molecular interactions of carbon nanotubes with the three key target proteins of HIV using computational chemistry approach. Armchair, chiral and zigzag CNTs were modeled and used as ligands for the interaction studies. The structure of the key proteins involved in HIV mediated infection namely HIV- Vpr, Nef and Gag proteins were collected from the PDB database. The docking studies were performed to quantify the interaction of the CNT with the three different disease targets. Results showed that the carbon nanotubes had high binding affinity to these proteins which confirms the antagonistic molecular interaction of carbon nanotubes to the disease targets. The modeled armchair carbon nanotubes had the binding affinities of -12.4 Kcal/mole, -20 Kcal/mole and -11.7 Kcal/mole with the Vpr, Nef and Gag proteins of HIV. Chiral CNTs also had the maximum affinity of -16.4 Kcal/mole to Nef. The binding affinity of chiral CNTs to Vpr and Gag was found to be -10.9 Kcal/mole and -10.3 Kcal/mole respectively. The zigzag CNTs had the binding affinity of -11.1 Kcal/mole with Vpr, -18.3 Kcal/mole with Nef and -10.9 with Gag respectively. The strong molecular interactions suggest the efficacy of CNTs for targeting the HIV mediated retroviral infections.

  17. Elucidation of Drug Metabolite Structural Isomers Using Molecular Modeling Coupled with Ion Mobility Mass Spectrometry.

    PubMed

    Reading, Eamonn; Munoz-Muriedas, Jordi; Roberts, Andrew D; Dear, Gordon J; Robinson, Carol V; Beaumont, Claire

    2016-02-16

    Ion mobility-mass spectrometry (IM-MS) in combination with molecular modeling offers the potential for small molecule structural isomer identification by measurement of their gas phase collision cross sections (CCSs). Successful application of this approach to drug metabolite identification would facilitate resource reduction, including animal usage, and may benefit other areas of pharmaceutical structural characterization including impurity profiling and degradation chemistry. However, the conformational behavior of drug molecules and their metabolites in the gas phase is poorly understood. Here the gas phase conformational space of drug and drug-like molecules has been investigated as well as the influence of protonation and adduct formation on the conformations of drug metabolite structural isomers. The use of CCSs, measured from IM-MS and molecular modeling information, for the structural identification of drug metabolites has also been critically assessed. Detection of structural isomers of drug metabolites using IM-MS is demonstrated and, in addition, a molecular modeling approach has been developed offering rapid conformational searching and energy assessment of candidate structures which agree with experimental CCSs. Here it is illustrated that isomers must possess markedly dissimilar CCS values for structural differentiation, the existence and extent of CCS differences being ionization state and molecule dependent. The results present that IM-MS and molecular modeling can inform on the identity of drug metabolites and highlight the limitations of this approach in differentiating structural isomers.

  18. Analysis of conjugation of chloramphenicol and hemoglobin by fluorescence, circular dichroism and molecular modeling

    NASA Astrophysics Data System (ADS)

    Ding, Fei; Liu, Wei; Sun, Ye; Yang, Xin-Ling; Sun, Ying; Zhang, Li

    2012-01-01

    Chloramphenicol is a low cost, broad spectrum, highly active antibiotic, and widely used in the treatment of serious infections, including typhoid fever and other life-threatening infections of the central nervous system and respiratory tract. The purpose of the present study was to examine the conjugation of chloramphenicol with hemoglobin (Hb) and compared with albumin at molecular level, utilizing fluorescence, UV/vis absorption, circular dichroism (CD) as well as molecular modeling. Fluorescence data indicate that drug bind Hb generate quenching via static mechanism, this corroborates UV/vis absorption measurements that the ground state complex formation with an affinity of 10 4 M -1, and the driving forces in the Hb-drug complex are hydrophilic interactions and hydrogen bonds, as derived from computational model. The accurate binding site of drug has been identified from the analysis of fluorescence and molecular modeling, α1β2 interface of Hb was assigned to possess high-affinity for drug, which located at the β-37 Trp nearby. The structural investigation of the complexed Hb by synchronous fluorescence, UV/vis absorption, and CD observations revealed some degree of Hb structure unfolding upon complexation. Based on molecular modeling, we can draw the conclusion that the binding affinity of drug with albumin is superior, compared with Hb. These phenomena can provide salient information on the absorption, distribution, pharmacology, and toxicity of chloramphenicol and other drugs which have analogous configuration with chloramphenicol.

  19. Investigation of oxygen self-diffusion in PuO2 by combining molecular dynamics with thermodynamic calculations

    SciTech Connect

    Saltas, V.; Chroneos, A.; Cooper, Michael William D.; Fitzpatrick, M. E.; Vallianatos, F.

    2016-01-01

    In the present work, the defect properties of oxygen self-diffusion in PuO2 are investigated over a wide temperature (300–1900 K) and pressure (0–10 GPa) range, by combining molecular dynamics simulations and thermodynamic calculations. Based on the well-established cBΩ thermodynamic model which connects the activation Gibbs free energy of diffusion with the bulk elastic and expansion properties, various point defect parameters such as activation enthalpy, activation entropy, and activation volume were calculated as a function of T and P. Molecular dynamics calculations provided the necessary bulk properties for the proper implementation of the thermodynamic model, in the lack of any relevant experimental data. The estimated compressibility and the thermal expansion coefficient of activation volume are found to be more than one order of magnitude greater than the corresponding values of the bulk plutonia. As a result, the diffusion mechanism is discussed in the context of the temperature and pressure dependence of the activation volume.

  20. Investigation of oxygen self-diffusion in PuO2 by combining molecular dynamics with thermodynamic calculations

    DOE PAGES

    Saltas, V.; Chroneos, A.; Cooper, Michael William D.; ...

    2016-01-01

    In the present work, the defect properties of oxygen self-diffusion in PuO2 are investigated over a wide temperature (300–1900 K) and pressure (0–10 GPa) range, by combining molecular dynamics simulations and thermodynamic calculations. Based on the well-established cBΩ thermodynamic model which connects the activation Gibbs free energy of diffusion with the bulk elastic and expansion properties, various point defect parameters such as activation enthalpy, activation entropy, and activation volume were calculated as a function of T and P. Molecular dynamics calculations provided the necessary bulk properties for the proper implementation of the thermodynamic model, in the lack of any relevantmore » experimental data. The estimated compressibility and the thermal expansion coefficient of activation volume are found to be more than one order of magnitude greater than the corresponding values of the bulk plutonia. As a result, the diffusion mechanism is discussed in the context of the temperature and pressure dependence of the activation volume.« less

  1. Molecular modelling of miraculin: Structural analyses and functional hypotheses.

    PubMed

    Paladino, Antonella; Costantini, Susan; Colonna, Giovanni; Facchiano, Angelo M

    2008-02-29

    Miraculin is a plant protein that displays the peculiar property of modifying taste by swiching sour into a sweet taste. Its monomer is flavourless at all pH as well as at high concentration; the dimer form elicits its taste-modifying activity at acidic pH; a tetrameric form is also reported as active. Two histidine residues, located in exposed regions, are the main responsible of miraculin activity, as demonstrated by mutagenesis studies. Since structural data of miraculin are not available, we have predicted its three-dimensional structure and simulated both its dimer and tetramer forms by comparative modelling and molecular docking techniques. Finally, molecular dynamics simulations at different pH conditions have indicated that at acidic pH the dimer assumes a widely open conformation, in agreement with the hypotheses coming from other studies.

  2. Molecular modeling of methyl-α-Neu5Ac analogues docked against cholera toxin--a molecular dynamics study.

    PubMed

    Blessy, J Jino; Sharmila, D Jeya Sundara

    2015-02-01

    Molecular modeling of synthetic methyl-α-Neu5Ac analogues modified in C-9 position was investigated by molecular docking and molecular dynamics (MD) simulation methods. Methyl-α-Neu5Ac analogues were docked against cholera toxin (CT) B subunit protein and MD simulations were carried out for three Methyl-α-Neu5Ac analogue-CT complexes (30, 10 and 10 ns) to estimate the binding activity of cholera toxin-Methyl-α-Neu5Ac analogues using OPLS_2005 force field. In this study, direct and water mediated hydrogen bonds play a vital role that exist between the methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ)-cholera toxin active site residues. The Energy plot, RMSD and RMSF explain that the simulation was stable throughout the simulation run. Transition of phi, psi and omega angle for the complex was calculated. Molecular docking studies could be able to identify the binding mode of methyl-α-Neu5Ac analogues in the binding site of cholera toxin B subunit protein. MD simulation for Methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ), Methyl-α-9-N-acetyl-9-deoxy-9-amino-Neu5Ac and Methyl-α-9-N-biphenyl-4-acetyl-deoxy-amino-Neu5Ac complex with CT B subunit protein was carried out, which explains the stable nature of interaction. These methyl-α-Neu5Ac analogues that have computationally acceptable pharmacological properties may be used as novel candidates for drug design for cholera disease.

  3. A computational kinetic model of diffusion for molecular systems

    NASA Astrophysics Data System (ADS)

    Teo, Ivan; Schulten, Klaus

    2013-09-01

    Regulation of biomolecular transport in cells involves intra-protein steps like gating and passage through channels, but these steps are preceded by extra-protein steps, namely, diffusive approach and admittance of solutes. The extra-protein steps develop over a 10-100 nm length scale typically in a highly particular environment, characterized through the protein's geometry, surrounding electrostatic field, and location. In order to account for solute energetics and mobility of solutes in this environment at a relevant resolution, we propose a particle-based kinetic model of diffusion based on a Markov State Model framework. Prerequisite input data consist of diffusion coefficient and potential of mean force maps generated from extensive molecular dynamics simulations of proteins and their environment that sample multi-nanosecond durations. The suggested diffusion model can describe transport processes beyond microsecond duration, relevant for biological function and beyond the realm of molecular dynamics simulation. For this purpose the systems are represented by a discrete set of states specified by the positions, volumes, and surface elements of Voronoi grid cells distributed according to a density function resolving the often intricate relevant diffusion space. Validation tests carried out for generic diffusion spaces show that the model and the associated Brownian motion algorithm are viable over a large range of parameter values such as time step, diffusion coefficient, and grid density. A concrete application of the method is demonstrated for ion diffusion around and through the Eschericia coli mechanosensitive channel of small conductance ecMscS.

  4. Commute Maps: Separating Slowly Mixing Molecular Configurations for Kinetic Modeling.

    PubMed

    Noé, Frank; Banisch, Ralf; Clementi, Cecilia

    2016-11-08

    Identification of the main reaction coordinates and building of kinetic models of macromolecular systems require a way to measure distances between molecular configurations that can distinguish slowly interconverting states. Here we define the commute distance that can be shown to be closely related to the expected commute time needed to go from one configuration to the other, and back. A practical merit of this quantity is that it can be easily approximated from molecular dynamics data sets when an approximation of the Markov operator eigenfunctions is available, which can be achieved by the variational approach to approximate eigenfunctions of Markov operators, also called variational approach of conformation dynamics (VAC) or the time-lagged independent component analysis (TICA). The VAC or TICA components can be scaled such that a so-called commute map is obtained in which Euclidean distance corresponds to the commute distance, and thus kinetic models such as Markov state models can be computed based on Euclidean operations, such as standard clustering. In addition, the distance metric gives rise to a quantity we call total kinetic content, which is an excellent score to rank input feature sets and kinetic model quality.

  5. A computational kinetic model of diffusion for molecular systems

    PubMed Central

    Teo, Ivan; Schulten, Klaus

    2013-01-01

    Regulation of biomolecular transport in cells involves intra-protein steps like gating and passage through channels, but these steps are preceded by extra-protein steps, namely, diffusive approach and admittance of solutes. The extra-protein steps develop over a 10–100 nm length scale typically in a highly particular environment, characterized through the protein's geometry, surrounding electrostatic field, and location. In order to account for solute energetics and mobility of solutes in this environment at a relevant resolution, we propose a particle-based kinetic model of diffusion based on a Markov State Model framework. Prerequisite input data consist of diffusion coefficient and potential of mean force maps generated from extensive molecular dynamics simulations of proteins and their environment that sample multi-nanosecond durations. The suggested diffusion model can describe transport processes beyond microsecond duration, relevant for biological function and beyond the realm of molecular dynamics simulation. For this purpose the systems are represented by a discrete set of states specified by the positions, volumes, and surface elements of Voronoi grid cells distributed according to a density function resolving the often intricate relevant diffusion space. Validation tests carried out for generic diffusion spaces show that the model and the associated Brownian motion algorithm are viable over a large range of parameter values such as time step, diffusion coefficient, and grid density. A concrete application of the method is demonstrated for ion diffusion around and through the Eschericia coli mechanosensitive channel of small conductance ecMscS. PMID:24089741

  6. Generalized Potential Energy Finite Elements for Modeling Molecular Nanostructures.

    PubMed

    Chatzieleftheriou, Stavros; Adendorff, Matthew R; Lagaros, Nikos D

    2016-10-24

    The potential energy of molecules and nanostructures is commonly calculated in the molecular mechanics formalism by superimposing bonded and nonbonded atomic energy terms, i.e. bonds between two atoms, bond angles involving three atoms, dihedral angles involving four atoms, nonbonded terms expressing the Coulomb and Lennard-Jones interactions, etc. In this work a new, generalized numerical simulation is presented for studying the mechanical behavior of three-dimensional nanostructures at the atomic scale. The energy gradient and Hessian matrix of such assemblies are usually computed numerically; a potential energy finite element model is proposed herein where these two components are expressed analytically. In particular, generalized finite elements are developed that express the interactions among atoms in a manner equivalent to that invoked in simulations performed based on the molecular dynamics method. Thus, the global tangent stiffness matrix for any nanostructure is formed as an assembly of the generalized finite elements and is directly equivalent to the Hessian matrix of the potential energy. The advantages of the proposed model are identified in terms of both accuracy and computational efficiency. In the case of popular force fields (e.g., CHARMM), the computation of the Hessian matrix by implementing the proposed method is of the same order as that of the gradient. This analysis can be used to minimize the potential energy of molecular systems under nodal loads in order to derive constitutive laws for molecular systems where the entropy and solvent effects are neglected and can be approximated as solids, such as double stranded DNA nanostructures. In this context, the sequence dependent stretch modulus for some typical base pairs step is calculated.

  7. Investigation of molecular mechanisms and regulatory pathways of pro-angiogenic nanorods

    NASA Astrophysics Data System (ADS)

    Nethi, Susheel Kumar; Veeriah, Vimal; Barui, Ayan Kumar; Rajendran, Saranya; Mattapally, Saidulu; Misra, Sanjay; Chatterjee, Suvro; Patra, Chitta Ranjan

    2015-05-01

    Angiogenesis, a process involving the growth of new blood vessels from the pre-existing vasculature, plays a crucial role in various pathophysiological conditions. We have previously demonstrated that europium hydroxide [EuIII(OH)3] nanorods (EHNs) exhibit pro-angiogenic properties through the generation of reactive oxygen species (ROS) and mitogen activated protein kinase (MAPK) activation. Considering the enormous implication of angiogenesis in cardiovascular diseases (CVDs) and cancer, it is essential to understand in-depth molecular mechanisms and signaling pathways in order to develop the most efficient and effective alternative treatment strategy for CVDs. However, the exact underlying mechanism and cascade signaling pathways behind the pro-angiogenic properties exhibited by EHNs still remain unclear. Herein, we report for the first time that the hydrogen peroxide (H2O2), a redox signaling molecule, generated by these EHNs activates the endothelial nitric oxide synthase (eNOS) that promotes the nitric oxide (NO) production in a PI3K (phosphoinositide 3-kinase)/Akt dependent manner, eventually triggering angiogenesis. We intensely believe that the investigation and understanding of the in-depth molecular mechanism and signaling pathways of EHNs induced angiogenesis will help us in developing an effective alternative treatment strategy for cardiovascular related and ischemic diseases where angiogenesis plays an important role.Angiogenesis, a process involving the growth of new blood vessels from the pre-existing vasculature, plays a crucial role in various pathophysiological conditions. We have previously demonstrated that europium hydroxide [EuIII(OH)3] nanorods (EHNs) exhibit pro-angiogenic properties through the generation of reactive oxygen species (ROS) and mitogen activated protein kinase (MAPK) activation. Considering the enormous implication of angiogenesis in cardiovascular diseases (CVDs) and cancer, it is essential to understand in-depth molecular

  8. Molecular Simulations of the Vapor-Liquid Phase Interfaces of Pure Water Modeled with the SPC/E and the TIP4P/2005 Molecular Models

    NASA Astrophysics Data System (ADS)

    Vinš, Václav; Celný, David; Planková, Barbora; Němec, Tomáš; Duška, Michal; Hrubý, Jan

    2016-03-01

    In our previous study [Planková et al., EPJWeb. Conf. 92, 02071 (2015)], several molecular simulations of vapor-liquid phase interfaces for pure water were performed using the DL_POLY Classic software. The TIP4P/2005 molecular model was successfully used for the modeling of the density profile and the thickness of phase interfaces together with the temperature dependence of the surface tension. In the current study, the extended simple point charge (SPC/E) model for water was employed for the investigation of vapor-liquid phase interfaces over a wide temperature range from 250 K to 600 K. The TIP4P/2005 model was also used with the temperature step of 25 K to obtain more consistent data compared to our previous study. Results of the new simulations are in a good agreement with most of the literature data. TIP4P/2005 provides better results for the saturated liquid density with its maximum close to 275 K, while SPC/E predicts slightly better saturated vapor density. Both models give qualitatively correct representation for the surface tension of water. The maximum absolute deviation from the IAPWS standard for the surface tension of ordinary water is 10.4 mN · m-1 and 4.1 mN · m-1 over the temperature range from 275 K to 600 K in case of SPC/E and TIP4P/2005, respectively.

  9. Probing the molecular interaction of triazole fungicides with human serum albumin by multispectroscopic techniques and molecular modeling.

    PubMed

    Zhang, Jing; Zhuang, Shulin; Tong, Changlun; Liu, Weiping

    2013-07-31

    Triazole fungicides, one category of broad-spectrum fungicides, are widely applied in agriculture and medicine. The extensive use leads to many residues and casts potential detrimental effects on aquatic ecosystems and human health. After exposure of the human body, triazole fungicides may penetrate into the bloodstream and interact with plasma proteins. Whether they could have an impact on the structure and function of proteins is still poorly understood. By using multispectroscopic techniques and molecular modeling, the interaction of several typical triazole fungicides with human serum albumin (HSA), the major plasma protein, was investigated. The steady-state and time-resolved fluorescence spectra manifested that static type, due to complex formation, was the dominant mechanism for fluorescence quenching. Structurally related binding modes speculated by thermodynamic parameters agreed with the prediction of molecular modeling. For triadimefon, hydrogen bonding with Arg-218 and Arg-222 played an important role, whereas for imazalil, myclobutanil, and penconazole, the binding process was mainly contributed by hydrophobic and electrostatic interactions. Via alterations in three-dimensional fluorescence and circular dichroism spectral properties, it was concluded that triazoles could induce slight conformational and some microenvironmental changes of HSA. It is anticipated that these data can provide some information for possible toxicity risk of triazole fungicides to human health and be helpful in reinforcing the supervision of food safety.

  10. Pharmacophore modeling, in silico screening, molecular docking and molecular dynamics approaches for potential alpha-delta bungarotoxin-4 inhibitors discovery

    PubMed Central

    Kumar, R. Barani; Suresh, M. Xavier; Priya, B. Shanmuga

    2015-01-01

    Background: The alpha-delta bungartoxin-4 (α-δ-Bgt-4) is a potent neurotoxin produced by highly venomous snake species, Bungarus caeruleus, mainly targeting neuronal acetylcholine receptors (nAchRs) and producing adverse biological malfunctions leading to respiratory paralysis and mortality. Objective: In this study, we predicted the three-dimensional structure of α-δ-Bgt-4 using homology modeling and investigated the conformational changes and the key residues responsible for nAchRs inhibiting activity. Materials and Methods: From the selected plants, which are traditionally used for snake bites, the active compounds are taken and performed molecular interaction studies and also used for modern techniques like pharmacophore modeling and mapping and absorption, distribution, metabolism, elimination and toxicity analysis which may increase the possibility of success. Results: Moreover, 100's of drug-like compounds were retrieved and analyzed through computational virtual screening and allowed for pharmacokinetic profiling, molecular docking and dynamics simulation. Conclusion: Finally the top five drug-like compounds having competing level of inhibition toward α-δ-Bgt-4 toxin were suggested based on their interaction with α-δ-Bgt-4 toxin. PMID:26109766

  11. Nonlocal continuum model and molecular dynamics for free vibration of single-walled carbon nanotubes.

    PubMed

    Hu, Yan-Gao; Liew, K M; Wang, Q

    2011-12-01

    Free transverse, longitudinal and torsional vibrations of single-walled carbon nanotubes (SWCNTs) are investigated through nonlocal beam model, nonlocal rod model and verified by molecular dynamics (MD) simulations. The nonlocal Timoshenko beam model offers a better prediction of the fundamental frequencies of shorter SWCNTs, such as a (5, 5) SWCNT shorter than 3.5 nm, than local beam models. The nonlocal rod model is employed to study the longitudinal and torsional vibrations of SWCNT and found to enable a good prediction of the MD results for shorter SWCNTs. Nonlocal and local continuum models provide a good agreement with MD results for relatively longer SWCNTs, such as (5, 5) SWCNTs longer than 3.5 nm. The scale parameter in nonlocal beam and rod models is estimated by calibrations from MD results.

  12. Improved molecular collision models for nonequilibrium rarefied gases

    NASA Astrophysics Data System (ADS)

    Parsons, Neal

    The Direct Simulation Monte Carlo (DSMC) method typically used to model thermochemical nonequilibrium rarefied gases requires accurate total collision cross sections, reaction probabilities, and molecular internal energy exchange models. However, the baseline total cross sections are often determined from extrapolations of relatively low-temperature viscosity data, reaction probabilities are defined such that experimentally determined equilibrium reaction rates are replicated, and internal energy relaxation models are phenomenological in nature. Therefore, these models have questionable validity in modeling strongly nonequilibrium gases with temperatures greater than those possible in experimental test facilities. To rectify this deficiency, the Molecular Dynamics/Quasi-Classical Trajectories (MD/QCT) method can be used to accurately compute total collision cross sections, reaction probabilities, and internal energy exchange models based on first principles for hypervelocity collision conditions. In this thesis, MD/QCT-based models were used to improve simulations of two unique nonequilibrium rarefied gas systems: the Ionian atmosphere and hypersonic shocks in Earth's atmosphere. The Jovian plasma torus flows over Io at ≈ 57 km/s, inducing high-speed collisions between atmospheric SO2 and the hypervelocity plasma's O atoms and ions. The DSMC method is well-suited to model the rarefied atmosphere, so MD/QCT studies are therefore conducted to improve DSMC collision models of the critical SO2-O collision pair. The MD/QCT trajectory simulations employed a new potential energy surface that was developed using a ReaxFF fit to a set of ab initio calculations. Compared to the MD/QCT results, the baseline DSMC models are found to significantly under-predict total cross sections, use reaction probabilities that are unrealistically high, and give unphysical internal energies above the dissociation energy for non-reacting inelastic collisions and under-predicts post

  13. Molecular Modeling of the Misfolded Insulin Subunit and Amyloid Fibril

    PubMed Central

    Choi, Jay H.; May, Barnaby C.H.; Wille, Holger; Cohen, Fred E.

    2009-01-01

    Abstract Insulin, a small hormone protein comprising 51 residues in two disulfide-linked polypeptide chains, adopts a predominantly α-helical conformation in its native state. It readily undergoes protein misfolding and aggregates into amyloid fibrils under a variety of conditions. Insulin is a unique model system in which to study protein fibrillization, since its three disulfide bridges are retained in the fibrillar state and thus limit the conformational space available to the polypeptide chains during misfolding and fibrillization. Taking into account this unique conformational restriction, we modeled possible monomeric subunits of the insulin amyloid fibrils using β-solenoid folds, namely, the β-helix and β-roll. Both models agreed with currently available biophysical data. We performed molecular dynamics simulations, which allowed some limited insights into the relative structural stability, suggesting that the β-roll subunit model may be more stable than the β-helix subunit model. We also constructed β-solenoid-based insulin fibril models and conducted fiber diffraction simulation to identify plausible fibril architectures of insulin amyloid. A comparison of simulated fiber diffraction patterns of the fibril models to the experimental insulin x-ray fiber diffraction data suggests that the model fibers composed of six twisted β-roll protofilaments provide the most reasonable fit to available experimental diffraction patterns and previous biophysical studies. PMID:20006956

  14. Modeling of growth factor-receptor systems: from molecular-level protein interaction networks to whole-body compartment models

    PubMed Central

    Wu, Florence T.H.; Stefanini, Marianne O.; Mac Gabhann, Feilim; Popel, Aleksander S.

    2010-01-01

    Most physiological processes are subjected to molecular regulation by growth factors, which are secreted proteins that activate chemical signal transduction pathways through binding of specific cell-surface receptors. One particular growth factor system involved in the in vivo regulation of blood vessel growth is called the vascular endothelial growth factor (VEGF) system. Computational and numerical techniques are well-suited to handle the molecular complexity (the number of binding partners involved, including ligands, receptors, and inert binding sites) and multi-scale nature (intra-tissue vs. inter-tissue transport and local vs. systemic effects within an organism) involved in modeling growth factor system interactions and effects. This paper introduces a variety of in silico models that seek to recapitulate different aspects of VEGF system biology at various spatial and temporal scales: molecular-level kinetic models focus on VEGF ligand-receptor interactions at and near the endothelial cell surface; meso-scale single-tissue 3D models can simulate the effects of multi-cellular tissue architecture on the spatial variation in VEGF ligand production and receptor activation; compartmental modeling allows efficient prediction of average interstitial VEGF concentrations and cell-surface VEGF signaling intensities across multiple large tissue volumes, permitting the investigation of whole-body inter-tissue transport (e.g., vascular permeability and lymphatic drainage). The given examples will demonstrate the utility of computational models in aiding both basic science and clinical research on VEGF systems biology. PMID:19897104

  15. Tunneling of electrons via rotor-stator molecular interfaces: Combined ab initio and model study

    NASA Astrophysics Data System (ADS)

    Petreska, Irina; Ohanesjan, Vladimir; Pejov, Ljupčo; Kocarev, Ljupčo

    2016-07-01

    Tunneling of electrons through rotor-stator anthracene aldehyde molecular interfaces is studied with a combined ab initio and model approach. Molecular electronic structure calculated from first principles is utilized to model different shapes of tunneling barriers. Together with a rectangular barrier, we also consider a sinusoidal shape that captures the effects of the molecular internal structure more realistically. Quasiclassical approach with the Simmons' formula for current density is implemented. Special attention is paid on conformational dependence of the tunneling current. Our results confirm that the presence of the side aldehyde group enhances the interesting electronic properties of the pure anthracene molecule, making it a bistable system with geometry dependent transport properties. We also investigate the transition voltage and we show that conformation-dependent field emission could be observed in these molecular interfaces at realistically low voltages. The present study accompanies our previous work where we investigated the coherent transport via strongly coupled delocalized orbital by application of Non-equilibrium Green's Function Formalism.

  16. A molecular-thermodynamic model for polyelectrolyte solutions

    NASA Astrophysics Data System (ADS)

    Jiang, Jianwen; Liu, Honglai; Hu, Ying; Prausnitz, J. M.

    1998-01-01

    Polyelectrolyte solutions are modeled as freely tangent-jointed, charged hard-sphere chains and corresponding counterions in a continuum medium with permitivity ɛ. By adopting the sticky-point model, the Helmholtz function for polyelectrolyte solutions is derived through the r-particle cavity-correlation function (CCF) for chains of sticky, charged hard spheres. The r-CCF is approximated by a product of effective nearest-neighbor two-particle CCFs; these are determined from the hypernetted-chain and mean-spherical closures (HNC/MSA) inside and outside the hard core, respectively, for the integral equation theory for electrolytes. The colligative properties are given as explicit functions of a scaling parameter Γ that can be estimated by a simple iteration procedure. Osmotic pressures, osmotic coefficients, and activity coefficients are calculated for model solutions with various chain lengths. They are in good agreement with molecular simulation and experimental results.

  17. A molecular-thermodynamic model for polyelectrolyte solutions

    SciTech Connect

    Jiang, J.; Liu, H.; Hu, Y.; Prausnitz, J.M.

    1998-01-01

    Polyelectrolyte solutions are modeled as freely tangent-jointed, charged hard-sphere chains and corresponding counterions in a continuum medium with permitivity {var_epsilon}. By adopting the sticky-point model, the Helmholtz function for polyelectrolyte solutions is derived through the r-particle cavity-correlation function (CCF) for chains of sticky, charged hard spheres. The r-CCF is approximated by a product of effective nearest-neighbor two-particle CCFs; these are determined from the hypernetted-chain and mean-spherical closures (HNC/MSA) inside and outside the hard core, respectively, for the integral equation theory for electrolytes. The colligative properties are given as explicit functions of a scaling parameter {Gamma} that can be estimated by a simple iteration procedure. Osmotic pressures, osmotic coefficients, and activity coefficients are calculated for model solutions with various chain lengths. They are in good agreement with molecular simulation and experimental results. {copyright} {ital 1998 American Institute of Physics.}

  18. Probing Molecular Docking in a Charged Model Binding Site

    PubMed Central

    Brenk, Ruth; Vetter, Stefan W.; Boyce, Sarah E.; Goodin, David B.; Shoichet, Brian K.

    2011-01-01

    A model binding site was used to investigate charge–charge interactions in molecular docking. This simple site, a small (180 Å3) engineered cavity in cyctochrome c peroxidase (CCP), is negatively charged and completely buried from solvent, allowing us to explore the balance between electrostatic energy and ligand desolvation energy in a system where many of the common approximations in docking do not apply. A database with about 5300 molecules was docked into this cavity. Retrospective testing with known ligands and decoys showed that overall the balance between electrostatic interaction and desolvation energy was captured. More interesting were prospective docking scre”ens that looked for novel ligands, especially those that might reveal problems with the docking and energy methods. Based on screens of the 5300 compound database, both high-scoring and low-scoring molecules were acquired and tested for binding. Out of 16 new, high-scoring compounds tested, 15 were observed to bind. All of these were small heterocyclic cations. Binding constants were measured for a few of these, they ranged between 20 μM and 60 μM. Crystal structures were determined for ten of these ligands in complex with the protein. The observed ligand geometry corresponded closely to that predicted by docking. Several low-scoring alkyl amino cations were also tested and found to bind. The low docking score of these molecules owed to the relatively high charge density of the charged amino group and the corresponding high desolvation penalty. When the complex structures of those ligands were determined, a bound water molecule was observed interacting with the amino group and a backbone carbonyl group of the cavity. This water molecule mitigates the desolvation penalty and improves the interaction energy relative to that of the “naked” site used in the docking screen. Finally, six low-scoring neutral molecules were also tested, with a view to looking for false negative predictions

  19. Geometric and electrostatic modeling using molecular rigidity functions

    DOE PAGES

    Mu, Lin; Xia, Kelin; Wei, Guowei

    2017-03-01

    Geometric and electrostatic modeling is an essential component in computational biophysics and molecular biology. Commonly used geometric representations admit geometric singularities such as cusps, tips and self-intersecting facets that lead to computational instabilities in the molecular modeling. Our present work explores the use of flexibility and rigidity index (FRI), which has a proved superiority in protein B-factor prediction, for biomolecular geometric representation and associated electrostatic analysis. FRI rigidity surfaces are free of geometric singularities. We propose a rigidity based Poisson–Boltzmann equation for biomolecular electrostatic analysis. These approaches to surface and electrostatic modeling are validated by a set of 21 proteins.more » Our results are compared with those of established methods. Finally, being smooth and analytically differentiable, FRI rigidity functions offer excellent curvature analysis, which characterizes concave and convex regions on protein surfaces. Polarized curvatures constructed by using the product of minimum curvature and electrostatic potential is shown to predict potential protein–ligand binding sites.« less

  20. Towards Accurate Molecular Modeling of Plastic Bonded Explosives

    NASA Astrophysics Data System (ADS)

    Chantawansri, T. L.; Andzelm, J.; Taylor, D.; Byrd, E.; Rice, B.

    2010-03-01

    There is substantial interest in identifying the controlling factors that influence the susceptibility of polymer bonded explosives (PBXs) to accidental initiation. Numerous Molecular Dynamics (MD) simulations of PBXs using the COMPASS force field have been reported in recent years, where the validity of the force field in modeling the solid EM fill has been judged solely on its ability to reproduce lattice parameters, which is an insufficient metric. Performance of the COMPASS force field in modeling EMs and the polymeric binder has been assessed by calculating structural, thermal, and mechanical properties, where only fair agreement with experimental data is obtained. We performed MD simulations using the COMPASS force field for the polymer binder hydroxyl-terminated polybutadiene and five EMs: cyclotrimethylenetrinitramine, 1,3,5,7-tetranitro-1,3,5,7-tetra-azacyclo-octane, 2,4,6,8,10,12-hexantirohexaazazisowurzitane, 2,4,6-trinitro-1,3,5-benzenetriamine, and pentaerythritol tetranitate. Predicted EM crystallographic and molecular structural parameters, as well as calculated properties for the binder will be compared with experimental results for different simulation conditions. We also present novel simulation protocols, which improve agreement between experimental and computation results thus leading to the accurate modeling of PBXs.

  1. Protein flexibility and ligand recognition: challenges for molecular modeling.

    PubMed

    Spyrakis, Francesca; BidonChanal, Axel; Barril, Xavier; Luque, F Javier

    2011-01-01

    The intrinsic dynamics of macromolecules is an essential property to relate the structure of biomolecular systems with their function in the cell. In the field of ligand-receptor recognition, numerous evidences have revealed the limitations of the lock-and-key theory, and the need to elaborate models that take into account the inherent plasticity of biomolecules, such as the induced-fit model or the existence of an ensemble of pre-equilibrated conformations. Depending on the nature of the target system, ligand binding can be associated with small local adjustments in side chains or even the backbone to large-scale motions of structural fragments, domains or even subunits. Reproducing the inherent flexibility of biomolecules has thus become one of the most challenging issues in molecular modeling and simulation studies, as it has direct implications in our understanding of the structure-function relationships, but even in areas such as virtual screening and structure-based drug discovery. Given the intrinsic limitation of conventional simulation tools, only events occurring in short time scales can be reproduced at a high accuracy level through all-atom techniques such as Molecular Dynamics simulations. However, larger structural rearrangements demand the use of enhanced sampling methods relying on modified descriptions of the biomolecular system or the potential surface. This review illustrates the crucial role that structural plasticity plays in mediating ligand recognition through representative examples. In addition, it discusses some of the most powerful computational tools developed to characterize the conformational flexibility in ligand-receptor complexes.

  2. Investigate the Binding of Catechins to Trypsin Using Docking and Molecular Dynamics Simulation

    PubMed Central

    Cui, Fengchao; Yang, Kecheng; Li, Yunqi

    2015-01-01

    To explore the inhibitory mechanism of catechins for digestive enzymes, we investigated the binding mode of catechins to a typical digestive enzyme-trypsin and analyzed the structure-activity relationship of catechins, using an integration of molecular docking, molecular dynamics simulation and binding free energy calculation. We found that catechins with different structures bound to a conservative pocket S1 of trypsin, which is comprised of residues 189–195, 214–220 and 225–228. In the trypsin-catechin complexes, Asp189 by forming strong hydrogen bonding, and Gln192, Trp215 and Gly216 through hydrophobic interactions, all significantly contribute to the binding of catechins. The number and the position of hydroxyl and aromatic groups, the structure of stereoisomers, and the orientation of catechins in the binding pocket S1 of trypsin all affect the binding affinity. The binding affinity is in the order of Epigallocatechin gallate (EGCG) > Epicatechin gallate (ECG) > Epicatechin (EC) > Epigallocatechin (EGC), and 2R-3R EGCG shows the strongest binding affinity out of other stereoisomers. Meanwhile, the synergic conformational changes of residues and catechins were also analyzed. These findings will be helpful in understanding the knowledge of interactions between catechins and trypsin and referable for the design of novel polyphenol based functional food and nutriceutical formulas. PMID:25938485

  3. Investigation of molecular mechanisms and regulatory pathways of pro-angiogenic nanorods†

    PubMed Central

    Nethi, Susheel Kumar; Veeriah, Vimal; Barui, Ayan Kumar; Rajendran, Saranya; Mattapally, Saidulu; Misra, Sanjay

    2016-01-01

    Angiogenesis, a process involving the growth of new blood vessels from the pre-existing vasculature, plays a crucial role in various pathophysiological conditions. We have previously demonstrated that europium hydroxide [EuIII(OH)3] nanorods (EHNs) exhibit pro-angiogenic properties through the generation of reactive oxygen species (ROS) and mitogen activated protein kinase (MAPK) activation. Considering the enormous implication of angiogenesis in cardiovascular diseases (CVDs) and cancer, it is essential to understand in-depth molecular mechanisms and signaling pathways in order to develop the most efficient and effective alternative treatment strategy for CVDs. However, the exact underlying mechanism and cascade signaling pathways behind the pro-angiogenic properties exhibited by EHNs still remain unclear. Herein, we report for the first time that the hydrogen peroxide (H2O2), a redox signaling molecule, generated by these EHNs activates the endothelial nitric oxide synthase (eNOS) that promotes the nitric oxide (NO) production in a PI3K (phosphoinositide 3-kinase)/Akt dependent manner, eventually triggering angiogenesis. We intensely believe that the investigation and understanding of the in-depth molecular mechanism and signaling pathways of EHNs induced angiogenesis will help us in developing an effective alternative treatment strategy for cardiovascular related and ischemic diseases where angiogenesis plays an important role. PMID:25963768

  4. Molecular and chemical investigations and comparisons of biomaterials for ocular surface regeneration.

    PubMed

    Kim, Yeon-Hee; Jin, Kyung-Hyun; Kim, Jae Hyung; Park, Dong Jin; Choi, Samjin; Park, Hun-Kuk

    2014-03-01

    This study investigated and compared the ultrastructural and chemical properties of representative biomaterials for ocular surface regeneration: a human amniotic membrane (AM) in a basal plate, a human AM in reflected chorion, a preserved AM, and a human corneo-scleral tissue. Assessments of the morphological differences in the extracellular matrices were evaluated by hematoxylin-eosin, Masson's trichrome (for total collagen), and picrosirius-red (for newly synthesized collagen) staining. Assessments of the changes in the molecular structures and chemical compositions of the biomaterials for ocular surface regeneration were evaluated by Raman spectroscopy. A placental AM (52 %) was a dense and thick collagenous structure compared to a reflected AM (23 %). The spectroscopy did not obtain any structural information for a preserved AM. The cornea group (100 %, control) and sclera group (104 %) showed the collagen lamellae and interfibrillar spacing, and a slight inflammatory reaction with more fibrous and granulomatous tissues. There was a formation of newly synthesized collagen in a placental AM, while there were few collagen components in a reflected AM. Human AM tissues showed consistent Raman spectra and the characteristic collagen bands, similar to the corneal and scleral tissues. Therefore, these findings suggest that human placental AM and reflected AM are structurally suitable for scleral and corneal surface regeneration, respectively, while human placental or preserved AM and reflected AM are molecularly and chemically suitable for corneal and scleral surface regeneration, respectively.

  5. Structural analysis and investigation of molecular properties of Cefpodoxime acid, a third generation antibiotic

    NASA Astrophysics Data System (ADS)

    Suganthi, S.; Balu, P.; Sathyanarayanamoorthi, V.; Kannappan, V.; Kamil, M. G. Mohamed; Kumar, R.

    2016-03-01

    Extensive quantum mechanical studies are carried out on Cefpodoxime acid (CA), a new generation drug by Hartree-Fock (HF) and B3LYP methods to understand the structural and spectral characteristics of the molecule. The most stable geometry of the molecule was optimized and the bond parameters were reported. The spectroscopic properties of this pharmaceutically important compound were investigated by FT-IR, FT-Raman, UV and 1H NMR techniques. The scaled vibrational frequencies of CA in the ground state are calculated by HF and B3LYP methods with 6-311++G (d, p) basis set and compared with the observed FT-IR and FT-Raman spectra. The vibrational spectral analysis indicates the presence of two intra molecular hydrogen bonds in the molecule which is supported by theoretical study. 1H NMR chemical shifts (δ) were calculated for the CA molecule and compared with the experimental values. The theoretical electronic absorption spectral data in water and ethanol solvents were computed by TD-DFT method. UV-Vis absorption spectra of CA are recorded in these two solvents and compared with theoretical spectra. The spectral data and natural bond orbital (NBO) analysis confirm the occurrence of intra molecular interactions in CA. The electronic distribution, in conjunction with electrophilicity index of CA was used to establish the active site and type of interaction between CA and beta lactamases. Mulliken population analysis on atomic charges is also carried out and thermodynamic properties of the title compound are calculated.

  6. Molecular-Level Investigations of Nucleation Mechanisms and Kinetics of Formation of Environmental Nanoparticles

    SciTech Connect

    Young-Shin Jun; Glenn A. Waychunas

    2007-04-19

    Environmental nanoparticles are often poorly-crystalline or metastable structures, whose kinetics of formation and growth are poorly understood. Further, the sorption or growth of nanoparticles on mineral surfaces may control the mineral surface's reactivity and modify its ability to influence contaminant transport. Due to the characteristic length scale, a holistic understanding of the nucleation mechanisms and kinetics of nanoparticle formation on mineral surfaces is difficult to achieve with traditional methodology. In this work, our intent is to determine the molecular nature of nucleation on surfaces, the kinetics of surface nucleation and growth, and the effect of crystal surface topology using new synchrotron-based techniques. We have approached these objectives by: (1) combining state-of-the-art crystal-truncation rod diffraction (CTR) and grazing incidence x-ray absorption fine structure spectroscopy (GIXAS) techniques to investigate the three-dimensional molecular-scale geometry of silicate monomer sorption on the r-plane of hematite; and (2) developing a new grazing-incidence small angle x-ray scattering (GISAXS) setup at SSRL (0.08 nm{sup -1} < q < 8 nm{sup -1}) to explore the initial development of environmental nanoparticles on various mineral surfaces. This study also includes complementary techniques such as atomic force microscopy (AFM), bulk SAXS, dynamic light scattering (DLS), XRD, and TEM.

  7. Who Scared the Cat? A Molecular Crime Scene Investigation Laboratory Exercise†

    PubMed Central

    Ott, Laura E.; Carson, Susan D.

    2016-01-01

    This introductory laboratory exercise gives first-year life science majors or nonmajors an opportunity to gain knowledge and experience in basic bioinformatics and molecular biology laboratory techniques and analysis in the context of a mock crime scene investigation. In this laboratory, students determine if a human (Lady) or dog (Kona) committed the fictional crime of scaring a cat. Students begin by performing in silico PCR using provided dog- and human-specific PCR primers to determine the sequences to be amplified and predict PCR amplicon sizes. They then BLAST (Basic Local Alignment Search Tool) the in silico PCR results to confirm that the PCR primers are designed to amplify genomic fragments of the cardiac actin gene in both dogs and humans. Finally, they use DNA quantification techniques, PCR, and agarose gel electrophoresis to identify the culprit and they confirm results by analyzing Sanger sequencing. Student learning gains were demonstrated by successful execution of the lab and by analysis and interpretation of data in the completion of laboratory reports. The student learning gains were also demonstrated by increased performance on a post-laboratory assessment compared to the pre-assessment. A post-activity assessment also revealed that students perceived gains in the skills and conceptual knowledge associated with the student learning outcomes. Finally, assessment of this introductory molecular biology and bio-informatics activity reveals that it allows first-year students to develop higher-order data analysis and interpretation skills. PMID:28101273

  8. Molecular structure and spectral investigations of 3,5-Di-tert-butyl-o-benzoquinone

    NASA Astrophysics Data System (ADS)

    Yilmaz, M.; Aydin, B.; Dogan, O.; Dereli, O.

    2017-01-01

    Conformational analysis of 3,5-Di-tert-butyl-o-benzoquinone molecule was performed and two stable conformers were determined by B3LYP/6-311++G(d,p). Using the most stable one, molecular structural parameters, vibrational frequencies were calculated by B3LYP/6-311++G(d,p), B3LYP/6-31G(d) and BLYP/6-31G(d,p) levels of theory. The FT-IR spectrum of the compound was recorded in the region 4000-550 cm-1. The Raman spectrum was also recorded in the region 3500-100 cm-1. Calculated results were compared with experimental counterparts. The best results were obtained from B3LYP/6-311++G(d,p) calculations. Experimental 13C and 1H NMR data of tittle compound were taken from literature and the calculated results compared with these data. Vibrational and NMR band assignments were performed. HOMO-LUMO energies, molecular electrostatic potentials and thermodynamic properties were also given for further investigations of our structure.

  9. Investigation on surface molecular conformations and pervaporation performance of the poly(vinyl alcohol) (PVA) membrane.

    PubMed

    Zhang, Wei; Zhang, Zhennan; Wang, Xinping

    2009-05-01

    A simple method of changing pre-treatment temperature in the course of film formation was used to tune the surface structures of PVA membranes. Surface structure and property of the resulting membranes were characterized by X-ray photoelectron spectroscopy (XPS), sum frequency generation (SFG) vibrational spectroscopy, and contact angle measurements. The results show that PVA have different molecular conformations at the membrane surface while those membranes were prepared at different pre-treatment temperature. At higher pre-treatment temperatures, polar acetoxyl residues and hydroxyl groups of the PVA chains oriented in a more orderly fashion, as induced by the faster evaporation of water. When the membranes were in air, CH(3) groups adjacent to the acetoxyl groups covered the surface in order to minimize the surface free energy, while backbones of the PVA were rarely observed. These surfaces exhibited a hydrophilic nature upon contact with water due to rapid surface reconstruction. Conversely, at lower pre-treatment temperatures, the backbone CH(2) groups dominated the surface, forming a less hydrophilic surface. When the PVA membranes were employed to separate ethanol/water mixtures, it was found that the PVA membranes with more hydrophilic surface exhibited higher water selectivity. Our investigation indicates that molecular conformations on the membrane surface have considerable influence on pervaporation performance.

  10. Who Scared the Cat? A Molecular Crime Scene Investigation Laboratory Exercise.

    PubMed

    Ott, Laura E; Carson, Susan D

    2016-12-01

    This introductory laboratory exercise gives first-year life science majors or nonmajors an opportunity to gain knowledge and experience in basic bioinformatics and molecular biology laboratory techniques and analysis in the context of a mock crime scene investigation. In this laboratory, students determine if a human (Lady) or dog (Kona) committed the fictional crime of scaring a cat. Students begin by performing in silico PCR using provided dog- and human-specific PCR primers to determine the sequences to be amplified and predict PCR amplicon sizes. They then BLAST (Basic Local Alignment Search Tool) the in silico PCR results to confirm that the PCR primers are designed to amplify genomic fragments of the cardiac actin gene in both dogs and humans. Finally, they use DNA quantification techniques, PCR, and agarose gel electrophoresis to identify the culprit and they confirm results by analyzing Sanger sequencing. Student learning gains were demonstrated by successful execution of the lab and by analysis and interpretation of data in the completion of laboratory reports. The student learning gains were also demonstrated by increased performance on a post-laboratory assessment compared to the pre-assessment. A post-activity assessment also revealed that students perceived gains in the skills and conceptual knowledge associated with the student learning outcomes. Finally, assessment of this introductory molecular biology and bio-informatics activity reveals that it allows first-year students to develop higher-order data analysis and interpretation skills.

  11. Molecular investigation of transmission of human immunodeficiency virus type 1 in a criminal case.

    PubMed

    Machuca, R; Jørgensen, L B; Theilade, P; Nielsen, C

    2001-09-01

    Very few criminal cases involving human immunodeficiency virus type 1 (HIV-1) transmission have been described. We report on an HIV-1 transmission case with a child being infected by an HIV-1-positive man. The objective was to determine through molecular epidemiology and phylogenetic analyses whether HIV-1 from the HIV-1-positive man could be the source of infection in the HIV-1-positive child, as claimed by the authorities. We conducted genetic analysis of three different parts of the HIV-1 genome (gag, pol, and env) by PCR, direct-sequencing, and phylogenetic analyses. We used maximum likelihood, maximum parsimony, and neighbor-joining methods for the phylogenetic analyses to investigate whether the sequences from the man and the child were related. We found that the viral sequences from the man and the child formed separate clusters in all of the phylogenetic analyses compared to the local controls. A unique amino acid deletion was identified in the C2-V3-C3 region of the env gene in the virus from the man and the child. These results were used in the criminal court to elucidate whether the virus from the man was related to the virus from the child. In summary, the results from the phylogenetic analyses, the sequence distances between the virus from the man and the virus from the child, and the identification of the unique molecular fingerprint in the env gene together indicated that the virus from the man and the virus from the child were epidemiologically linked.

  12. Lessons from molecular modeling human α-L-iduronidase.

    PubMed

    Figueiredo, Danieli Forgiarini; Antunes, Dinler A; Rigo, Maurício M; Mendes, Marcus F A; Silva, Jader P; Mayer, Fabiana Q; Matte, Ursula; Giugliani, Roberto; Vieira, Gustavo F; Sinigaglia, Marialva

    2014-11-01

    Human α-L-iduronidase (IDUA) is a member of glycoside hydrolase family and is involved in the catabolism of glycosaminoglycans (GAGs), heparan sulfate (HS) and dermatan sulfate (DS). Mutations in this enzyme are responsible for mucopolysaccharidosis I (MPS I), an inherited lysosomal storage disorder. Despite great interest in determining and studying this enzyme structure, the lack of a high identity to templates and other technical issues have challenged both bioinformaticians and crystallographers, until the recent publication of an IDUA crystal structure (PDB: 4JXP). In the present work, four alternative IDUA models, generated and evaluated prior to crystallographic determination, were compared to the 4JXP structure. A combined analysis using several viability assessment tools and molecular dynamics simulations highlights the strengths and limitations of different comparative modeling protocols, all of which are based on the same low identity template (only 22%). Incorrect alignment between the target and template was confirmed to be a major bottleneck in homology modeling, regardless of the modeling software used. Moreover, secondary structure analysis during a 50ns simulation seems to be useful for indicating alignment errors and structural instabilities. The best model was achieved through the combined use of Phyre 2 and Modeller, suggesting the use of this protocol for the modeling of other proteins that still lack high identity templates.

  13. Molecular Communication Modeling of Antibody-Mediated Drug Delivery Systems.

    PubMed

    Chahibi, Youssef; Akyildiz, Ian F; Balasubramaniam, Sasitharan; Koucheryavy, Yevgeni

    2015-07-01

    Antibody-mediated Drug Delivery Systems (ADDS) are emerging as one of the most encouraging therapeutic solutions for treating several diseases such as human cancers. ADDS use small molecules (antibodies) that propagate in the body and bind selectively to their corresponding receptors (antigens) expressed at the surface of the diseased cells. In this paper, the Molecular Communication (MC) paradigm, where information is conveyed through the concentration of molecules, is advocated for the engineering of ADDS and modeling their complex behavior, to provide a realistic model without the over-complication of system biology models, and the limitations of experimental approaches. The peculiarities of antibodies, including their anisotropic transport and complex electrochemical structure, are taken into account to develop an analytical model of the ADDS transport and antigen-binding kinetics. The end-to-end response of ADDS, from the drug injection to the drug absorption, is mathematically derived based on the geometry of the antibody molecule, the electrochemical structure of the antibody-antigen complex, and the physiology of the patient. The accuracy of the MC model is validated by finite-element (COMSOL) simulations. The implications of the complex interplay between the transport and kinetics parameters on the performance of ADDS are effectively captured by the proposed MC model. The MC model of ADDS will enable the discovery and optimization of drugs in a versatile, cost-efficient, and reliable manner.

  14. Multiensemble Markov models of molecular thermodynamics and kinetics.

    PubMed

    Wu, Hao; Paul, Fabian; Wehmeyer, Christoph; Noé, Frank

    2016-06-07

    We introduce the general transition-based reweighting analysis method (TRAM), a statistically optimal approach to integrate both unbiased and biased molecular dynamics simulations, such as umbrella sampling or replica exchange. TRAM estimates a multiensemble Markov model (MEMM) with full thermodynamic and kinetic information at all ensembles. The approach combines the benefits of Markov state models-clustering of high-dimensional spaces and modeling of complex many-state systems-with those of the multistate Bennett acceptance ratio of exploiting biased or high-temperature ensembles to accelerate rare-event sampling. TRAM does not depend on any rate model in addition to the widely used Markov state model approximation, but uses only fundamental relations such as detailed balance and binless reweighting of configurations between ensembles. Previous methods, including the multistate Bennett acceptance ratio, discrete TRAM, and Markov state models are special cases and can be derived from the TRAM equations. TRAM is demonstrated by efficiently computing MEMMs in cases where other estimators break down, including the full thermodynamics and rare-event kinetics from high-dimensional simulation data of an all-atom protein-ligand binding model.

  15. Coupled continuum and molecular model of flow through fibrous filter

    NASA Astrophysics Data System (ADS)

    Zhao, Shunliu; Povitsky, Alex

    2013-11-01

    A coupled approach combining the continuum boundary singularity method (BSM) and the molecular direct simulation Monte Carlo (DSMC) is developed and validated using Taylor-Couette flow and the flow about a single fiber confined between two parallel walls. In the proposed approach, the DSMC is applied to an annular region enclosing the fiber and the BSM is employed in the entire flow domain. The parameters used in the DSMC and the coupling procedure, such as the number of simulated particles, the cell size, and the size of the coupling zone are determined by inspecting the accuracy of pressure drop obtained for the range of Knudsen numbers between zero and unity. The developed approach is used to study flowfield of fibrous filtration flows. It is observed that in the partial-slip flow regime, Kn ⩽ 0.25, the results obtained by the proposed coupled BSM-DSMC method match the solution by BSM combined with the heuristic partial-slip boundary conditions. For transition molecular-to-continuum Knudsen numbers, 0.25 < Kn ⩽ 1, the difference in pressure drop and velocity between these two approaches is significant. This difference increases with the Knudsen number that confirms the usefulness of coupled continuum and molecular methods in numerical modeling of transition low Reynolds number flows in fibrous filters.

  16. Variable soft sphere molecular model for air species

    NASA Astrophysics Data System (ADS)

    Koura, Katsuhisa; Matsumoto, Hiroaki

    1992-05-01

    A reliable set of cross-section parameters of the variable soft sphere (VSS) molecular model is determined for the Monte Carlo simulation of air species from the transport collision integrals or potential parameters provided by Cubley and Mason (1975) over the high-temperature range 300-15,000 K. The VSS cross-section parameters for the inverse-power-law potential are also determined from the viscosity coefficients recommended by Maitland and Smith (1972) for common species in the low (20-300 K) and high (300-2000 K) temperature ranges.

  17. Variable soft sphere molecular model for air species

    NASA Astrophysics Data System (ADS)

    Koura, Katsuhisa; Matsumoto, Hiroaki

    1992-05-01

    A reliable set of cross-section parameters of the variable soft sphere (VSS) molecular model is determined for the Monte Carlo simulation of air species from the transport collision integrals or potential parameters provided by Cubley and Mason [Phys. Fluids 18, 1109 (1975)] over the high-temperature range 300-15 000 K. The VSS cross-section parameters for the inverse-power-law potential are also determined from the viscosity coefficients recommended by Maitland and Smith [J. Chem. Eng. Data 17, 150 (1972)] for common species in the low (20-300 K) and high (300-2000 K) temperature ranges.

  18. Kinetic modeling based probabilistic segmentation for molecular images.

    PubMed

    Saad, Ahmed; Hamarneh, Ghassan; Möller, Torsten; Smith, Ben

    2008-01-01

    We propose a semi-supervised, kinetic modeling based segmentation technique for molecular imaging applications. It is an iterative, self-learning algorithm based on uncertainty principles, designed to alleviate low signal-to-noise ratio (SNR) and partial volume effect (PVE) problems. Synthetic fluorodeoxyglucose (FDG) and simulated Raclopride dynamic positron emission tomography (dPET) brain images with excessive noise levels are used to validate our algorithm. We show, qualitatively and quantitatively, that our algorithm outperforms state-of-the-art techniques in identifying different functional regions and recovering the kinetic parameters.

  19. Mesoscale modeling of molecular machines: cyclic dynamics and hydrodynamical fluctuations.

    PubMed

    Cressman, Andrew; Togashi, Yuichi; Mikhailov, Alexander S; Kapral, Raymond

    2008-05-01

    Proteins acting as molecular machines can undergo cyclic internal conformational motions that are coupled to ligand binding and dissociation events. In contrast to their macroscopic counterparts, nanomachines operate in a highly fluctuating environment, which influences their operation. To bridge the gap between detailed microscopic and simple phenomenological descriptions, a mesoscale approach, which combines an elastic network model of a machine with a particle-based mesoscale description of the solvent, is employed. The time scale of the cyclic hinge motions of the machine prototype is strongly affected by hydrodynamical coupling to the solvent.

  20. Molecular modelling approaches for cystic fibrosis transmembrane conductance regulator studies.

    PubMed

    Odolczyk, Norbert; Zielenkiewicz, Piotr

    2014-07-01

    Cystic fibrosis (CF) is one of the most common genetic disorders, caused by loss of function mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. CFTR is a member of ATP-binding cassette (ABC) transporters superfamily and functions as an ATP-gated anion channel. This review summarises the vast majority of the efforts which utilised molecular modelling approaches to gain insight into the various aspects of CFTR protein, related to its structure, dynamic properties, function and interactions with other protein partners, or drug-like compounds, with emphasis to its relation to CF disease.

  1. Molecular dynamics investigation of the grain boundary migration hysteresis of nanocrystalline Ni under cyclic shear loading

    NASA Astrophysics Data System (ADS)

    Wang, Peng; Yang, Xinhua; Peng, Di

    2017-02-01

    The deformation behavior and grain boundary (GB) response of nanocrystalline Ni under cyclic shear loading are investigated by molecular dynamics simulations. The GB migration hysteresis phenomenon, in which the GB migration displacement lags behind the change in nominal shear strain, is observed in the symmetric tilt GBs for the first time. The elementary structure transformation occurring at the two end segments of the observed GB during GB migration produces a disordered and irreversible state, while the transformation in the middle segment is reversible. Both dislocation retraction and nucleation occur during unloading. Relatively large cyclic strain amplitudes lead to disordered GB segments of greater length, such that the residual GB migration displacement increases with increasing cyclic amplitude. GB migration hysteresis vanishes after the GB becomes immobile owing to a cyclic shear induced transition to a disordered state along its entire length.

  2. Interaction of sulfanilamide and sulfamethoxazole with bovine serum albumin and adenine: Spectroscopic and molecular docking investigations

    NASA Astrophysics Data System (ADS)

    Rajendiran, N.; Thulasidhasan, J.

    2015-06-01

    Interaction between sulfanilamide (SAM) and sulfamethoxazole (SMO) with BSA and DNA base (adenine) was investigated by UV-visible, fluorescence, cyclic voltammetry and molecular docking studies. Stern-Volmer fluorescence quenching constant (Ka) suggests SMO is more quenched with BSA/adenine than that of SAM. The distance r between donor (BSA/adenine) and acceptor (SAM and SMO) was obtained according to fluorescence resonance energy transfer (FRET). The results showed that hydrophobic forces, electrostatic interactions, and hydrogen bonds played vital roles in the SAM and SMO with BSA/adenine binding interaction. During the interaction, sulfa drugs could insert into the hydrophobic pocket, where the non-radioactive energy transfer from BSA/adenine to sulfa drugs occurred with high possibility. Cyclic voltammetry results suggested that when the drug concentration is increased, the anodic electrode potential deceased. The docking method indicates aniline group is interacted with the BSA molecules.

  3. Interaction of sulfanilamide and sulfamethoxazole with bovine serum albumin and adenine: spectroscopic and molecular docking investigations.

    PubMed

    Rajendiran, N; Thulasidhasan, J

    2015-06-05

    Interaction between sulfanilamide (SAM) and sulfamethoxazole (SMO) with BSA and DNA base (adenine) was investigated by UV-visible, fluorescence, cyclic voltammetry and molecular docking studies. Stern-Volmer fluorescence quenching constant (Ka) suggests SMO is more quenched with BSA/adenine than that of SAM. The distance r between donor (BSA/adenine) and acceptor (SAM and SMO) was obtained according to fluorescence resonance energy transfer (FRET). The results showed that hydrophobic forces, electrostatic interactions, and hydrogen bonds played vital roles in the SAM and SMO with BSA/adenine binding interaction. During the interaction, sulfa drugs could insert into the hydrophobic pocket, where the non-radioactive energy transfer from BSA/adenine to sulfa drugs occurred with high possibility. Cyclic voltammetry results suggested that when the drug concentration is increased, the anodic electrode potential deceased. The docking method indicates aniline group is interacted with the BSA molecules.

  4. Molecular dynamics investigation of dislocation pinning by a nanovoid in copper

    SciTech Connect

    Hatano, Takahiro; Matsui, Hideki

    2005-09-01

    The interaction between an edge dislocation and a void in copper is investigated by means of a molecular dynamics simulation. The depinning stresses of the leading partial and of the trailing partial show qualitatively different behaviors. The depinning stress of the trailing partial increases logarithmically with the void radius, while that of the leading partial behaves in a different manner due to the interaction between two partials. The pinning angle, which characterizes the obstacle strength, approaches zero when the void radius exceeds 3 nm. No temperature dependence is found in the critical stress and the critical angle. This is attributed to an absence of climb motion. It is also found that the distance between the void center and a glide plane asymmetrically affects the pinning strength.

  5. [Investigation on bioactive protective function of amino acids to insulin by molecular simulation].

    PubMed

    Li, Daixi; Zhai, Zhen; Guo, Baisong; Liu, Baolin; Zhang, Yan; Yu, Huaxing; Liu, Li; Yang, Chunsheng

    2014-08-01

    Heat sensitive protein medicines are increasingly exhibiting their critical importance on treatment of various diseases at present. But their popularization and application meet a great challenge because of their heat instability. In the present study, insulin was taken as a heat sensitive protein medicine and amino acid as bio-protective agent in order to investigate if these amino acids can protect the insulin from losing its bioactivity due to desiccation. The experiment was performed by using replica exchange molecular simulation (REMD) method and Gromacs software with Gromos96 (53a6) force field. The REMD results indicated that these amino acids could protect the bioactive structure of insulin during desiccation. The configurations of the protected insulin were preserved very well. Those results proved that amino acid is a kind of good bioactive protective agent for the heat sensitive protein medicines.

  6. Preliminary investigations into surface molecularly imprinted nanoparticles for Helicobacter pylori eradication

    PubMed Central

    Han, Jiaying; Sun, Yinjing; Hou, Jiapeng; Wang, Yuyan; Liu, Yu; Xie, Cao; Lu, Weiyue; Pan, Jun

    2015-01-01

    This paper reports investigations into the preparation and characterization of surface molecularly imprinted nanoparticles (SMINs) designed to adhere to Helicobacter pylori (H. pylori). Imprinted nanoparticles were prepared by the inverse microemulsion polymerization method. A fraction of Lpp20, an outer membrane protein of H. pylori known as NQA, was chosen as template and modified with myristic acid to facilitate its localization on the surface of the nanoparticles. The interaction between these SMINs with the template NQA were evaluated using surface plasmon resonance (SPR), change in zeta potential and fluorescence polarization (FP). The results were highly consistent in demonstrating a preferential recognition of the template NQA for SMINs compared with the control nanoparticles. In vitro experiments also indicate that such SMINs are able to adhere to H. pylori and may be useful for H. pylori eradication. PMID:26713273

  7. First-principles investigation of iron pentacarbonyl molecular solid phases at high pressure

    NASA Astrophysics Data System (ADS)

    Cong, Kien Nguyen; Steele, Brad A.; Landerville, Aaron C.; Oleynik, Ivan I.

    2017-01-01

    The polymeric phases of carbon monoxide (p-CO), an extended non-molecular solid, represent a new class of low-Z energetic materials. The presence of transition metal ions is believed to stabilize polymeric carbon monoxide (p-CO) at ambient conditions. Since p-CO forms at high pressures, it becomes important to investigate the high-pressure behavior of one of the potential precursors, iron pentacarbonyl Fe(CO)5. In this work, a first-principles evolutionary structure search method is used to determine the crystal phases of Fe(CO)5 at high pressure. The calculations predict the crystal structure of Phase I in agreement with experiment. Moreover, the previously unidentified crystal structure of Phase II is found. The calculated pressure-dependent Raman spectra are used to demonstrate that the changes in Raman spectra as a function of pressure observed in recent experiment can be explained without invoking a phase transition to a new phase III.

  8. Paramagnetic particle assemblies as colloidal models for atomic and molecular systems

    NASA Astrophysics Data System (ADS)

    Li, Dichuan

    2011-12-01

    Colloidal particles are ideal models for studying the behavior of atomic and molecular systems. They resemble their atomic and molecular analogues in that their dynamics are driven by thermal energy and their equilibrium properties are controlled by inter-particle interactions. Based on this analogy, it is reasonable to construct colloidal chains, where each particle represents a repeat unit, as models for polymers. The advantages of this system over molecular systems are its controllable rigidity, contour length and diameter, as well as the convenience to capture its instantaneous shape and position via video microscopy, which are not trivial to realize in molecular systems. By utilizing the dipolar properties of magnetic colloids, a number of groups have assembled semiflexible and rigid colloidal chains by cross-linking magnetic beads under a magnetic field using polymer linkers. Recently, efforts in constructing colloidal chains led even to anisotropic magnetic colloidal chains that mimic the detailed atomic arrangements of polymers. These properties make colloidal chains possible candidates for the classic bead-spring or bead-rod model systems for semiflexible and rigid polymers. In my thesis, I present a method for generating linear colloidal chain structures by linking surface functionalized paramagnetic particles using DNA. First, I investigate the force interactions between individual magnetic particles under different conditions to optimize the resulting chain stability. A systematic study the bending and rotational diffusion dynamics of the chains and their relationship with the DNA linking chemistry is presented. I then demonstrate their use as a ideal model system to study polymer dynamics In addition, a technique to measure short-range repulsive surface forces between these colloids with high precision was developed. Building on these repulsive force studies, a colloidal system to study 2-D phase transitions was created. This thesis provides insights

  9. Investigating the influence of effective parameters on molecular characteristics of bovine serum albumin nanoparticles

    NASA Astrophysics Data System (ADS)

    Rohiwal, S. S.; Satvekar, R. K.; Tiwari, A. P.; Raut, A. V.; Kumbhar, S. G.; Pawar, S. H.

    2015-04-01

    The protein nanoparticles formulation is a challenging task as they are prone to undergo conformational transitions while processing which may affect bioavailability for bioactive compounds. Herein, a modified desolvation method is employed to prepare Bovine Serum Albumin nanoparticles, with controllable particle size ranging from 100 to 300 nm and low polydispersity index. The factors influencing the size and structure of BSA NPs viz. protein concentration, pH and the conditions for purification are well investigated. The structure of BSA NPs is altered due to processing, and may affect the effective binding ability with drugs and bioactive compounds. With that aims, investigations of molecular characteristics of BSA NPs are carried out in detail by using spectroscopic techniques. UV-visible absorption and Fourier Transform Infrared demonstrate the alteration in protein structure of BSA NPs whereas the FT-Raman spectroscopy investigates changes in the secondary and tertiary structures of the protein. The conformational changes of BSA NPs are observed by change in fluorescence intensity and emission maximum wavelength of tryptophan residue by fluorescence spectroscopy. The field emission scanning electron and atomic force microscopy micrographs confirm the size and semi-spherical morphology of the BSA NPs. The effect of concentration and pH on particle size distribution is studied by particle size analyzer.

  10. Experimental Investigation of Molecular Species Formation in Metal Plasmas During Laser Ablation

    NASA Astrophysics Data System (ADS)

    Radousky, H.; Crowhurst, J.; Rose, T.; Armstrong, M.; Stavrou, E.; Zaug, J.; Weisz, D.; Azer, M.; Finko, M.; Curreli, D.

    2016-10-01

    Atomic and molecular spectra on metal plasmas generated by laser ablation have been measured using single, nominally 6-7 ns pulses at 1064 nm, and with energies less than 50 mJ. The primary goal for these studies is to constrain the physical and chemical mechanisms that control the distribution of radionuclides in fallout after a nuclear detonation. In this work, laser emission spectroscopy was used to obtain in situdata for vapor phase molecular species as they form in a controlled oxygen atmosphere for a variety of metals such as Fe, Al, as well as preliminary results for U. In particular, the ablation plumes created from these metals have been imaged with a resolution of 10 ns, and it is possible to observe the expansion of the plume out to 0.5 us. These data serve as one set of inputs for a semi-empirical model to describe the chemical fractionation of uranium during fallout formation. Prepared by LLNL under Contract DE-AC52-07NA27344. This project was sponsored by the Department of the Defense, Defense Threat Reduction Agency, under Grant Number HDTRA1-16-1-0020.

  11. A molecular model for epsilon-caprolactam-based intercalated polymer clay nanocomposite: Integrating modeling and experiments.

    PubMed

    Sikdar, Debashis; Katti, Dinesh R; Katti, Kalpana S

    2006-08-29

    In studying the morphology, molecular interactions, and physical properties of organically modified montmorillonite (OMMT) and polymer clay nanocomposites (PCNs) through molecular dynamics (MD), the construction of the molecular model of OMMT and PCN is important. Better understanding of interaction between various constituents of PCN will improve the design of polymer clay nanocomposite systems. MD is an excellent tool to study interactions, which require accurate modeling of PCN under consideration. Previously, the PCN models were constructed by different researchers on the basis of specific criteria such as minimum energy configuration, density of the polymer clay nanocomposite, and so forth. However, in this article we describe the development of models combining experimental and conventional molecular modeling to develop models, which are more representative of true intercalated PCN systems. The models were used for studying the morphological interactions and physical properties. These studies gave useful information regarding orientation of organic modifiers, area of coverage of organic modifiers over the interlayer clay surface, interaction of organic modifiers with clay in OMMT, interaction among different constituents of PCN, conformational and density change, and actual proportion of mixing of polymer with clay in PCN. We have X-ray diffraction and photoacoustic Fourier transform infrared spectroscopy to verify the model.

  12. Expedition Earth and Beyond: Student Scientist Guidebook. Model Research Investigation

    NASA Technical Reports Server (NTRS)

    Graff, Paige Valderrama

    2009-01-01

    The Expedition Earth and Beyond Student Scientist Guidebook is designed to help student researchers model the process of science and conduct a research investigation. The Table of Contents listed outlines the steps included in this guidebook

  13. Molecular modeling of calmodulin: a comparison with crystallographic data

    NASA Technical Reports Server (NTRS)

    McDonald, J. J.; Rein, R.

    1989-01-01

    Two methods of side-chain placement on a modeled protein have been examined. Two molecular models of calmodulin were constructed that differ in the treatment of side chains prior to optimization of the molecule. A virtual bond analysis program developed by Purisima and Scheraga was used to determine the backbone conformation based on 2.2 angstroms resolution C alpha coordinates for the molecules. In the first model, side chains were initially constructed in an extended conformation. In the second model, a conformational grid search technique was employed. Calcium ions were treated explicitly during energy optimization using CHARMM. The models are compared to a recently published refined crystal structure of calmodulin. The results indicate that the initial choices for side-chains, but also significant effects on the main-chain conformation and supersecondary structure. The conformational differences are discussed. Analysis of these and other methods makes possible the formulation of a methodology for more appropriate side-chain placement in modeled proteins.

  14. Multiensemble Markov models of molecular thermodynamics and kinetics

    PubMed Central

    Wu, Hao; Paul, Fabian; Noé, Frank

    2016-01-01

    We introduce the general transition-based reweighting analysis method (TRAM), a statistically optimal approach to integrate both unbiased and biased molecular dynamics simulations, such as umbrella sampling or replica exchange. TRAM estimates a multiensemble Markov model (MEMM) with full thermodynamic and kinetic information at all ensembles. The approach combines the benefits of Markov state models—clustering of high-dimensional spaces and modeling of complex many-state systems—with those of the multistate Bennett acceptance ratio of exploiting biased or high-temperature ensembles to accelerate rare-event sampling. TRAM does not depend on any rate model in addition to the widely used Markov state model approximation, but uses only fundamental relations such as detailed balance and binless reweighting of configurations between ensembles. Previous methods, including the multistate Bennett acceptance ratio, discrete TRAM, and Markov state models are special cases and can be derived from the TRAM equations. TRAM is demonstrated by efficiently computing MEMMs in cases where other estimators break down, including the full thermodynamics and rare-event kinetics from high-dimensional simulation data of an all-atom protein–ligand binding model. PMID:27226302

  15. Theoretical investigation of rotationally inelastic collisions of CH(X2Π ) with molecular hydrogen

    NASA Astrophysics Data System (ADS)

    Dagdigian, Paul J.

    2016-12-01

    We report calculations of state-to-state cross sections for collision-induced rotational transitions of CH(X2Π ) with molecular hydrogen. These calculations employed the diabatic matrix elements of the interaction potential determined by Dagdigian [J. Chem. Phys. 145, 114301 (2016)], which employed the multi-reference configuration-interaction method [MRCISD+Q(Davidson)]. Because of the presence of a deep well on the lower potential energy surface, the scattering calculations were carried out using the quantum statistical method of Manolopoulos and co-workers [Chem. Phys. Lett. 343, 356 (2001)]. The computed cross sections included contributions from direct scattering, as well as from the formation and decay of a collision complex. The magnitude of latter contribution was found to decrease significantly with increasing collision energy. Rotationally energy transfer rate constants were computed for this system since these are required for astrochemical modeling.

  16. Molecular interactions between amantadine and model cell membranes.

    PubMed

    Wu, Fu-Gen; Yang, Pei; Zhang, Chi; Li, Bolin; Han, Xiaofeng; Song, Minghu; Chen, Zhan

    2014-07-22

    Sum frequency generation (SFG) vibrational spectroscopy was applied to study molecular interactions between amantadine and substrate supported lipid bilayers serving as model cell membranes. Both isotopically asymmetric and symmetric lipid bilayers were used in the research. SFG results elucidated how the water-soluble drug, amantadine, influenced the packing state of each leaflet of a lipid bilayer and how the drugs affected the lipid flip-flop process. It is difficult to achieve such detailed molecular-level information using other analytical techniques. Especially, from the flip-flop rate change of isotopically asymmetric lipid bilayer induced by amantadine, important information on the drug-membrane interaction mechanism can be derived. The results show that amantadine can be associated with zwitterionic PC bilayers but has a negligible influence on the flip-flop behavior of PC molecules unless at high concentrations. Different effects of amantadine on the lipid bilayer were observed for the negatively charged DPPG bilayer; low concentration amantadine (e.g., 0.20 mM) in the subphase could immediately disturb the outer lipid leaflet and then the lipid associated amantadine molecules gradually reorganize to cause the outer leaflet to return to the original orderly packed state. Higher concentration amantadine (e.g., 5.0 mM) immediately disordered the packing state of the outer lipid leaflet. For both the high and low concentration cases, amantadine molecules only bind to the outer PG leaflet and cannot translocate to the inner layer. The presence of amantadine within the negatively charged lipid layers has certain implications for using liposomes as drug delivery carriers for amantadine. Besides, by using PC or PG bilayers with both leaflets deuterated, we were able to examine how amantadine is distributed and/or oriented within the lipid bilayer. The present work demonstrates that SFG results can provide an in-depth understanding of the molecular mechanisms of

  17. Consistent flamelet modeling of differential molecular diffusion for turbulent non-premixed flames

    NASA Astrophysics Data System (ADS)

    Wang, Haifeng

    2016-03-01

    Treating differential molecular diffusion correctly and accurately remains as a great challenge to the modeling of turbulent non-premixed combustion. The aim of this paper is to develop consistent modeling strategies for differential molecular diffusion in flamelet models. Two types of differential molecular diffusion models are introduced, linear differential diffusion models and nonlinear differential diffusion models. A multi-component turbulent mixing layer problem is analyzed in detail to gain insights into differential molecular diffusion and its characteristics, particularly the dependence of differential molecular diffusion on the Reynolds number and the Lewis number. These characteristics are then used to validate the differential molecular diffusion models. Finally, the new models are applied to the modeling of a series of laboratory-scale turbulent non-premixed jet flames with different Reynolds number (Sandia Flames B, C, and D) to further assess the models' performance.

  18. Investigating the molecular mechanisms of in-plane mechanochemistry on cantilever arrays.

    PubMed

    Watari, Moyu; Galbraith, Jane; Lang, Hans-Peter; Sousa, Marilyne; Hegner, Martin; Gerber, Christoph; Horton, Mike A; McKendry, Rachel A

    2007-01-24

    Free-standing cantilevers, which directly translate specific biochemical reactions into micromechanical motion, have recently attracted much attention as label-free biosensors and micro/nano robotic devices. To exploit this mechanochemical sensing technology, it is essential to develop a fundamental understanding of the origins of surface stress. Here we report a detailed study into the molecular basis of stress generation in aqueous environments focusing on the pH titration of model mercaptohexadecanoic acid self-assembled monolayers (SAMs), using in situ reference cantilevers coated with nonionizable hexadecanethiol SAMs. Semiautomated data analysis and a statistical model were developed to quantify cyclic deprotonation/protonation reactions on multiple arrays. In-plane force titrations were found to have the sensitivity to detect ionic hydrogen bond formation between protonated and nonprotonated carboxylic acid groups in the proximity of the surface pK1/2, which generated a mean tensile differential surface stress of +1.2 +/- 0.3 mN/m at pH 6.0, corresponding to 1 pN attractive force between two adjacent MHA molecules. Conversely, the magnitude of compressive differential surface stress was found to increase progressively with pH >/= 7.0, reaching a maximum of -14.5 +/- 0.5 mN/m at pH 9.0, attributed to enhanced electrostatic repulsion between deprotonated carboxylic acid groups. However, striking differences were observed in the micromechanical responses to different ionic strength and ion species present in the aqueous environment, highlighting the critical role of counter- and co-ions on surface stress. Our findings provide fundamental insights into the molecular mechanisms of in-plane mechanochemistry, which may be exploited for biosensing and nanoactuation applications.

  19. Spatial distribution of intra-molecular water and polymeric components in polyelectrolyte dendrimers revealed by small angle scattering investigations

    SciTech Connect

    Chen, Chun-Yu; Chen, Wei-Ren; Herwig, Kenneth W; Hong, Kunlun; Li, Xin; Liu, Emily; Liu, Yun; Smith, Gregory Scott; Wu, Bin; Yang, Jun; Do, Changwoo

    2011-01-01

    An experimental scheme using contrast variation small angle neutron scattering technique (SANS), is developed to investigate the structural characteristics of amine-terminated poly(amidoamine) dendrimers (PAMAM) solutions. The focus is placed on understanding the dependence of intra-dendrimer water and polymer distribution on molecular protonation, which can be precisely adjusted by tuning the pH value of solution. Assuming the spherical symmetry in the spatial arrangement of the constituent component of dendrimer, and the atomic ratio of hydrogen-to-deuterium for the solvent residing within the cavities of dendrimer is identical to that for the solvent outside dendrimer, the intra-dendrimer water distribution along the radial direction can be determined based on the model of coherent scattering cross section developed in this work. Moreover, our result clearly reveals an outward relocation of the peripheral groups, as well as the enhanced intra-dendrimer hydration, upon increasing the molecular protonation and therefore allows the determination of segmental backfolding in a quantitative manner. The connection between these charge-induced structural changes and our recently observed progressively active segmental dynamics is also discussed.

  20. Scanning tunneling microscope investigations of organic heterostructures prepared by a combination of self-assembly and molecular beam epitaxy

    NASA Astrophysics Data System (ADS)

    Staub, R.; Toerker, M.; Fritz, T.; Schmitz-Hübsch, T.; Sellam, F.; Leo, K.

    2000-01-01

    We report the realization of organic-organic heteroepitaxy by combining liquid-phase self-assembly with ultrahigh vacuum (UHV) gas-phase molecular beam epitaxy. As a model system, we have used self-assembled monolayers (SAMs) prepared by exposing an Au(111)-mica substrate to a dilute solution of decanethiol in ethanol, with subsequent evaporation of 3,4,9,10-perylene-tetracarboxylic-dianhydride (PTCDA) dye molecules. The well-known (3×3)R30° superstructure of almost upright standing molecules after chemisorption is replaced by the 11.5×3 (33.2 Å) pin-stripe phase with flat lying molecules when the samples are annealed in UHV and coverage decreases. The deposition of PTCDA induces reordering and displacement in the decanethiol SAM. Additional to the 33.2 Å periodicity, the previously reported 22 Å thiol stripe phase can be observed by scanning tunneling microscopy. Several PTCDA structures are observed: single and double rows of PTCDA that grow along decanethiol stripes on top of the flat-lying alkane chain groups, as well as densely packed PTCDA monolayer domains embedded into the thiol layer. These exhibit the well-known herringbone structure or a novel square lattice structure. We have also investigated thicker PTCDA islands and observed molecular resolution for a thickness of several monolayers. The structure of the three-dimensional islands can be identified as the α bulk modification.

  1. Aggregation of model asphaltenes: a molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Costa, J. L. L. F. S.; Simionesie, D.; Zhang, Z. J.; Mulheran, P. A.

    2016-10-01

    Natural asphaltenes are defined as polyaromatic compounds whose chemical composition and structure are dependent on their geological origin and production history, hence are regarded as complex molecules with aromatic cores and aliphatic tails that occur in the heaviest fraction of crude oil. The aggregation of asphaltenes presents a range of technical challenges to the production and processing of oil. In this work we study the behaviour of the model asphaltene-like molecule hexa-tert-butylhexa-peri-hexabenzocoronene (HTBHBC) using molecular dynamics simulation. It was found that the regular arrangement of the tert-butyl side chains prevents the formation of strongly-bound dimers by severely restricting the configurational space of the aggregation pathway. In contrast, a modified molecule with only 3 side chains is readily able to form dimers. This work therefore confirms the influence of the molecular structure of polyaromatic compounds on their aggregation mechanism, and reveals the unexpected design rules required for model systems that can mimic the behavior of asphaltenes.

  2. Aggregation of model asphaltenes: a molecular dynamics study.

    PubMed

    Costa, J L L F S; Simionesie, D; Zhang, Z J; Mulheran, P A

    2016-10-05

    Natural asphaltenes are defined as polyaromatic compounds whose chemical composition and structure are dependent on their geological origin and production history, hence are regarded as complex molecules with aromatic cores and aliphatic tails that occur in the heaviest fraction of crude oil. The aggregation of asphaltenes presents a range of technical challenges to the production and processing of oil. In this work we study the behaviour of the model asphaltene-like molecule hexa-tert-butylhexa-peri-hexabenzocoronene (HTBHBC) using molecular dynamics simulation. It was found that the regular arrangement of the tert-butyl side chains prevents the formation of strongly-bound dimers by severely restricting the configurational space of the aggregation pathway. In contrast, a modified molecule with only 3 side chains is readily able to form dimers. This work therefore confirms the influence of the molecular structure of polyaromatic compounds on their aggregation mechanism, and reveals the unexpected design rules required for model systems that can mimic the behavior of asphaltenes.

  3. The Applicability of Selected Evaluation Models to Evolving Investigative Designs.

    ERIC Educational Resources Information Center

    Smith, Nick L.; Hauer, Diane M.

    1990-01-01

    Ten evaluation models are examined in terms of their applicability to investigative, emergent design programs: Stake's portrayal, Wolf's adversary, Patton's utilization, Guba's investigative journalism, Scriven's goal-free, Scriven's modus operandi, Eisner's connoisseurial, Stufflebeam's CIPP, Tyler's objective based, and Levin's cost…

  4. Towards an integrated molecular model of plant-virus interactions.

    PubMed

    Elena, Santiago F; Rodrigo, Guillermo

    2012-12-01

    The application in recent years of network theory methods to the study of host-virus interactions is providing a new perspective to the way viruses manipulate the host to promote their own replication. An integrated molecular model of such pathosystems require three detailed maps describing, firstly, the interactions between viral elements, secondly, the interactions between host elements, and thirdly, the cross-interactions between viral and host elements. Here, we compile available information for Potyvirus infecting Arabidopsis thaliana. With an integrated model, it is possible to analyze the mode of virus action and how the perturbation of the virus targets propagates along the network. These studies suggest that viral pathogenicity results not only from the alteration of individual elements but it is a systemic property.

  5. [Targeted molecular therapy based on advanced cancer stem cell model].

    PubMed

    Hirao, Atsushi

    2015-08-01

    Improvement of cell purification and transplantation techniques have contributed to the identification of cell populations known as tumor-initiating cells (TICs). Although it was hypothesized that tumors are organized as hierarchies of tumor cells that are sustained by rare TICs, like normal tissue stem cells, there are several controversies towards such cancer stem cell model, e.g. reversible change of stem cell like population based on epigenetic changes, clonal genetic evolution and problems in xenotransplantation system. Despite complexity in cancer stem cell models, studies in cancer stem cell field have revealed that there are close relationship between cancer malignancy and stem cell properties, called "stemness". Understanding molecular mechanisms for controlling stemness would contribute to establishment of novel diagnostics or therapeutics for cancer.

  6. A Model of Molecular Emission from Protoplanetary Disks

    NASA Astrophysics Data System (ADS)

    Harrold, Samuel Thomas; Lacy, J.; Salyk, C.; Doty, S.

    2011-01-01

    We present results from a new model describing the mid-infrared emission of simple organic molecules from the protoplanetary disks of low-mass stars. We will test whether indicators of disk evolution, such as grain growth, dust settling, and dust crystallinity, enhance the emission of simple organic molecules in the mid-infrared, in particular that of HCN and C2H2, from the inner few AU of the disk. The Q branches of HCN at 13.9 um and of C2H2 at 13.7 um have been detected in the spectra of disks around T-Tauri stars using Spitzer's IRS (Carr & Najita, 2008). Our new model, pisco, calculates the steady-state disk structure and molecular level populations via non-LTE, 3D radiative transfer. The chemical abundances are determined through a chemical evolutionary code. This work is supported by the NSF GRFP.

  7. Interactive display of molecular models using a microcomputer system

    NASA Technical Reports Server (NTRS)

    Egan, J. T.; Macelroy, R. D.

    1980-01-01

    A simple, microcomputer-based, interactive graphics display system has been developed for the presentation of perspective views of wire frame molecular models. The display system is based on a TERAK 8510a graphics computer system with a display unit consisting of microprocessor, television display and keyboard subsystems. The operating system includes a screen editor, file manager, PASCAL and BASIC compilers and command options for linking and executing programs. The graphics program, written in USCD PASCAL, involves the centering of the coordinate system, the transformation of centered model coordinates into homogeneous coordinates, the construction of a viewing transformation matrix to operate on the coordinates, clipping invisible points, perspective transformation and scaling to screen coordinates; commands available include ZOOM, ROTATE, RESET, and CHANGEVIEW. Data file structure was chosen to minimize the amount of disk storage space. Despite the inherent slowness of the system, its low cost and flexibility suggests general applicability.

  8. Molecular modeling of pathogenesis-related proteins of family 5.

    PubMed

    Thompson, Claudia E; Fernandes, Cláudia L; de Souza, Osmar N; Salzano, Francisco M; Bonatto, Sandro L; Freitas, Loreta B

    2006-01-01

    The family of pathogenesis-related (PR) 5 proteins have diverse functions, and some of them are classified as thaumatins, osmotins, and inhibitors of alpha-amylase or trypsin. Although the specific function of many PR5 in plants is unknown, they are involved in the acquired systemic resistance and response to biotic stress, causing the inhibition of hyphal growth and reduction of spore germination, probably by a membrane permeabilization mechanism or by interaction with pathogen receptors. We have constructed three-dimensional models of four proteins belonging to the Rosaceae and Fagaceae botanical families by using the technique of comparative molecular modelling by homology. There are four main structural differences between all the PR5, corresponding to regions with replacements of amino acids. Folding and the secondary structures are very similar for all of them. However, the isoelectric point and charge distributions differ for each protein.

  9. Deformation-induced damage and recovery in model hydrogels - A molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Zidek, Jan; Milchev, Andrey; Jancar, Josef; Vilgis, Thomas A.

    2016-09-01

    Using molecular dynamics simulation of a model hybrid cross-link hydrogel, we investigate the network damage evolution and the related structure transformations. We model the hydrogel structure as a network-connected assembly of crosslinked clusters whereby deformation-induced damage is considered along with network recovery. The two principal mechanisms involved in hydrogel recovery from deformation include segment hops of the building structure units (segments) between clusters and cluster shape modification. These mechanisms act either instantaneously, or with a certain time delay after the onset of deformation. By elucidating the conditions under which one of the mechanisms prevails, one may design hydrogel materials with a desired response to deformation.

  10. A Cost-Effective Model for Digital Forensic Investigations

    NASA Astrophysics Data System (ADS)

    Overill, Richard; Kwan, Michael; Chow, Kam-Pui; Lai, Pierre; Law, Frank

    Because of the way computers operate, every discrete event potentially leaves a digital trace. These digital traces must be retrieved during a digital forensic investigation to prove or refute an alleged crime. Given resource constraints, it is not always feasible (or necessary) for law enforcement to retrieve all the related digital traces and to conduct comprehensive investigations. This paper attempts to address the issue by proposing a model for conducting swift, practical and cost-effective digital forensic investigations.

  11. A review of molecular modelling of electric double layer capacitors.

    PubMed

    Burt, Ryan; Birkett, Greg; Zhao, X S

    2014-04-14

    Electric double-layer capacitors are a family of electrochemical energy storage devices that offer a number of advantages, such as high power density and long cyclability. In recent years, research and development of electric double-layer capacitor technology has been growing rapidly, in response to the increasing demand for energy storage devices from emerging industries, such as hybrid and electric vehicles, renewable energy, and smart grid management. The past few years have witnessed a number of significant research breakthroughs in terms of novel electrodes, new electrolytes, and fabrication of devices, thanks to the discovery of innovative materials (e.g. graphene, carbide-derived carbon, and templated carbon) and the availability of advanced experimental and computational tools. However, some experimental observations could not be clearly understood and interpreted due to limitations of traditional theories, some of which were developed more than one hundred years ago. This has led to significant research efforts in computational simulation and modelling, aimed at developing new theories, or improving the existing ones to help interpret experimental results. This review article provides a summary of research progress in molecular modelling of the physical phenomena taking place in electric double-layer capacitors. An introduction to electric double-layer capacitors and their applications, alongside a brief description of electric double layer theories, is presented first. Second, molecular modelling of ion behaviours of various electrolytes interacting with electrodes under different conditions is reviewed. Finally, key conclusions and outlooks are given. Simulations on comparing electric double-layer structure at planar and porous electrode surfaces under equilibrium conditions have revealed significant structural differences between the two electrode types, and porous electrodes have been shown to store charge more efficiently. Accurate electrolyte and

  12. A n-vector model for charge transport in molecular semiconductors.

    PubMed

    Jackson, Nicholas E; Kohlstedt, Kevin L; Chen, Lin X; Ratner, Mark A

    2016-11-28

    We develop a lattice model utilizing coarse-grained molecular sites to study charge transport in molecular semiconducting materials. The model bridges atomistic descriptions and structureless lattice models by mapping molecular structure onto sets of spatial vectors isomorphic with spin vectors in a classical n-vector Heisenberg model. Specifically, this model incorporates molecular topology-dependent orientational and intermolecular coupling preferences, including the direct inclusion of spatially correlated transfer integrals and site energy disorder. This model contains the essential physics required to explicitly simulate the interplay of molecular topology and correlated structural disorder, and their effect on charge transport. As a demonstration of its utility, we apply this model to analyze the effects of long-range orientational correlations, molecular topology, and intermolecular interaction strength on charge motion in bulk molecular semiconductors.

  13. A n-vector model for charge transport in molecular semiconductors

    NASA Astrophysics Data System (ADS)

    Jackson, Nicholas E.; Kohlstedt, Kevin L.; Chen, Lin X.; Ratner, Mark A.

    2016-11-01

    We develop a lattice model utilizing coarse-grained molecular sites to study charge transport in molecular semiconducting materials. The model bridges atomistic descriptions and structureless lattice models by mapping molecular structure onto sets of spatial vectors isomorphic with spin vectors in a classical n-vector Heisenberg model. Specifically, this model incorporates molecular topology-dependent orientational and intermolecular coupling preferences, including the direct inclusion of spatially correlated transfer integrals and site energy disorder. This model contains the essential physics required to explicitly simulate the interplay of molecular topology and correlated structural disorder, and their effect on charge transport. As a demonstration of its utility, we apply this model to analyze the effects of long-range orientational correlations, molecular topology, and intermolecular interaction strength on charge motion in bulk molecular semiconductors.

  14. Characterization of the Interaction between Eupatorin and Bovine Serum Albumin by Spectroscopic and Molecular Modeling Methods

    PubMed Central

    Xu, Hongliang; Yao, Nannan; Xu, Haoran; Wang, Tianshi; Li, Guiying; Li, Zhengqiang

    2013-01-01

    This study investigated the interaction between eupatorin and bovine serum albumin (BSA) using ultraviolet-visible (UV-vis) absorption, fluorescence, synchronous fluorescence, circular dichroism (CD) spectroscopies, and molecular modeling at pH 7.4. Results of UV-vis and fluorescence spectroscopies illustrated that BSA fluorescence was quenched by eupatorin via a static quenching mechanism. Thermodynamic parameters revealed that hydrophobic and electrostatic interactions played major roles in the interaction. Moreover, the efficiency of energy transfer, and the distance between BSA and acceptor eupatorin, were calculated. The effects of eupatorin on the BSA conformation were analyzed using UV-vis, CD, and synchronous fluorescence. Finally, the binding of eupatorin to BSA was modeled using the molecular docking method. PMID:23839090

  15. Investigating the LGBTQ Responsive Model for Supervision of Group Work

    ERIC Educational Resources Information Center

    Luke, Melissa; Goodrich, Kristopher M.

    2013-01-01

    This article reports an investigation of the LGBTQ Responsive Model for Supervision of Group Work, a trans-theoretical supervisory framework to address the needs of lesbian, gay, bisexual, transgender, and questioning (LGBTQ) persons (Goodrich & Luke, 2011). Findings partially supported applicability of the LGBTQ Responsive Model for Supervision…

  16. Investigating Student Understanding of Quantum Physics: Spontaneous Models of Conductivity.

    ERIC Educational Resources Information Center

    Wittmann, Michael C.; Steinberg, Richard N.; Redish, Edward F.

    2002-01-01

    Investigates student reasoning about models of conduction. Reports that students often are unable to account for the existence of free electrons in a conductor and create models that lead to incorrect predictions and responses contradictory to expert descriptions of the physics involved. (Contains 36 references.) (Author/YDS)

  17. Molecular structure activity on pharmaceutical applications of Phenacetin using spectroscopic investigation

    NASA Astrophysics Data System (ADS)

    Madanagopal, A.; Periandy, S.; Gayathri, P.; Ramalingam, S.; Xavier, S.

    2017-01-01

    The pharmaceutical compound; Phenacetin was investigated by analyzing FT-IR, FT-Raman and 1H &13C NMR spectra. The hybrid efficient computational calculations performed for computing physical and chemical parameters. The cause of pharmaceutical activity due to the substitutions; carboxylic, methyl and amine groups in appropriate positions on the pedestal compound was deeply investigated. Moreover, 13C NMR and 1H NMR chemical shifts correlated with TMS standard to explain the truth of compositional ratio of base and ligand groups. The bathochromic shift due to chromophores over the energy levels in UV-Visible region was strongly emphasized the Anti-inflammatory chemical properties. The chemical stability was pronounced by the strong kubo gap which showed the occurring of charge transformation within the molecule. The occurrence of the chemical reaction was feasibly interpreted by Gibbs free energy profile. The standard vibrational analysis stressed the active participation of composed ligand groups for the existence of the analgesic as well as antipyretic properties of the Phenacetin compound. The strong dipole interaction energy utilization for the transition among non-vanishing donor and acceptor for composition of the molecular structure was interpreted.

  18. Molecular identification of python species: development and validation of a novel assay for forensic investigations.

    PubMed

    Ciavaglia, Sherryn A; Tobe, Shanan S; Donnellan, Stephen C; Henry, Julianne M; Linacre, Adrian M T

    2015-05-01

    Python snake species are often encountered in illegal activities and the question of species identity can be pertinent to such criminal investigations. Morphological identification of species of pythons can be confounded by many issues and molecular examination by DNA analysis can provide an alternative and objective means of identification. Our paper reports on the development and validation of a PCR primer pair that amplifies a segment of the mitochondrial cytochrome b gene that has been suggested previously as a good candidate locus for differentiating python species. We used this DNA region to perform species identification of pythons, even when the template DNA was of poor quality, as might be the case with forensic evidentiary items. Validation tests are presented to demonstrate the characteristics of the assay. Tests involved the cross-species amplification of this marker in non-target species, minimum amount of DNA template required, effects of degradation on product amplification and a blind trial to simulate a casework scenario that provided 100% correct identity. Our results demonstrate that this assay performs reliably and robustly on pythons and can be applied directly to forensic investigations where the presence of a species of python is in question.

  19. Influence of free surface nanorelief on the rear spallation threshold: Molecular-dynamics investigation

    NASA Astrophysics Data System (ADS)

    Mayer, Alexander E.; Ebel, Andrej A.

    2016-10-01

    By means of molecular dynamics simulation, we investigate the interaction of picosecond-duration compression pulses excited by a flat impactor with flat and nano-structured rear surfaces of copper and aluminum samples. It is shown that protrusions on the rear surface can increase the threshold value of the impact velocity, leading to spallation. As the shock wave reaches the perturbed rear surface, an unloading on the lateral surfaces of the protrusions begins; it leads to an intensive plastic deformation in the surface layer of metal. A part of the compression pulse energy is spent on the plastic deformation that restricts the rarefaction wave amplitude and suppresses the spall fracture. An increase in threshold velocity can be observed for all investigated thicknesses of the targets. The increase is substantial with respect to comparability between the protrusion height and the compression pulse width (the impactor thickness). Another condition is the ratio of the protrusion cross-section to the total surface area, which should be neither small nor large-approximately 0.3-0.4 for the best case. At high protrusion heights (higher than the compression pulse width), as well as at large protrusion cross sections, instability develops on the rear surface of the target and is accompanied by mass ejection. The instability violates the rear surface integrity and restricts the threshold velocity, although the loss of integrity in this case goes through mass ejection, not spallation.

  20. Molecular interaction study of flavonoid derivative 3d with human serum albumin using multispectroscopic and molecular modeling approach.

    PubMed

    Wei, Juntong; Jin, Feng; Wu, Qin; Jiang, Yuyang; Gao, Dan; Liu, Hongxia

    2014-08-01

    Human serum albumin (HSA) has been developed as a model protein to study drug-protein interaction. In the present work, the interaction between our synthesized flavonoid derivative 3d (possessing potent antitumor activity against HepG2 cells) and HSA was investigated using fluorescence spectroscopy, circular dichroism spectroscopy, UV-vis spectroscopy and molecular modeling approach. Fluorescence spectroscopy showed that the fluorescence of HSA can be quenched remarkably by 3d under physiological condition with a slight shift of maximum fluorescence emission bands from 360nm to 363nm. Calculated results from Stern-Volmer equation and modified Stern-Volmer equation indicated that the fluorescence was quenched by static quenching processing with association constant 5.26±0.04×10(4)L mol(-1) at 298K. After comprehensive consideration of the free energy change ΔG, enthalpy change ΔH and entropy change ΔS, electrostatic interactions were confirmed as the main factor that participate in stabilizing the 3d-HSA complex. Both dichroism spectroscopy and UV-vis spectroscopy indicated conformational change of HSA after binding to 3d. Moreover, the structure of HSA was loosened and the percentage of α-helix decreased with increasing concentration of 3d. Molecular modeling results demonstrated that 3d could bind to HSA well into subdomain IIA, which is related to its capability of deposition and delivery. Three cation-π interactions and three hydrogen bonds occurred between 3d and amino acid residuals ARG218, ARG222 and LYS199. In conclusion, flavonoid derivative 3d can bind to HSA with noncovalent bond in a relatively stable way, so it can be delivered by HSA in a circulatory system.

  1. Lanthanide and transition metal complexes of bioactive coumarins: molecular modeling and spectroscopic studies.

    PubMed

    Georgieva, I; Mihaylov, Tz; Trendafilova, N

    2014-06-01

    The present paper summarizes theoretical and spectroscopic investigations on a series of active coumarins and their lanthanide and transition metal complexes with application in medicine and pharmacy. Molecular modeling as well as IR, Raman, NMR and electronic spectral simulations at different levels of theory were performed to obtain important molecular descriptors: total energy, formation energy, binding energy, stability, conformations, structural parameters, electron density distribution, molecular electrostatic potential, Fukui functions, atomic charges, and reactive indexes. The computations are performed both in gas phase and in solution with consideration of the solvent effect on the molecular structural and energetic parameters. The investigations have shown that the advanced computational methods are reliable for prediction of the metal-coumarin binding mode, electron density distribution, thermodynamic properties as well as the strength and nature of the metal-coumarin interaction (not experimentally accessible) and correctly interpret the experimental spectroscopic data. Known results from biological tests for cytotoxic, antimicrobial, anti-fungal, spasmolytic and anti-HIV activities on the studied metal complexes are reported and discussed.

  2. Diffusion energy profiles in silica mesoporous molecular sieves modelled with the fragment molecular orbital method

    NASA Astrophysics Data System (ADS)

    Roskop, Luke; Fedorov, Dmitri G.; Gordon, Mark S.

    2013-07-01

    The fragment molecular orbital (FMO) method is used to model truncated portions of mesoporous silica nanoparticle (MSN) pores. The application of the FMO/RHF (restricted Hartree-Fock) method to MCM-41 type MSNs is discussed and an error analysis is given. The FMO/RHF method is shown to reliably approximate the RHF energy (error ∼0.2 kcal/mol), dipole moment (error ∼0.2 debye) and energy gradient (root mean square [RMS] error ∼0.2 × 10-3 a.u./bohr). Several FMO fragmentation schemes are employed to provide guidance for future applications to MSN models. An MSN pore model is functionalised with (phenyl)propyl substituents and the diffusion barrier for benzene passing through the pore is computed by the FMO/RHF-D method with the Grimme dispersion correction (RHF-D). For the reaction coordinates examined here, the maximum FMO/RHF-D interaction energies range from -0.3 to -5.8 kcal/mol.

  3. New AFM Techniques for Investigating Molecular Growth Mechanisms of Protein Crystals

    NASA Technical Reports Server (NTRS)

    Li, Huayu; Nadarajah, Arunan; Konnert, John H.; Pusey, Marc L.

    1998-01-01

    Atomic Force Microscopy (AFM) has emerged as a powerful technique for investigating protein crystal growth. Earlier AFM studies were among the first to demonstrate that these crystals grew by dislocation and 2D nucleation growth mechanisms [1]. These investigations were restricted to the micron range where only surface features, such as dislocation hillocks and 2D islands are visible. Most AFM instruments can scan at higher resolutions and have the potential to resolve individual protein molecules at nanometer ranges. Such scans are essential for determining the molecular packing arrangements on crystal faces and for probing the growth process at the molecular level. However, at this resolution the AFM tip influences the image produced, with the resulting image being a convolution of the tip shape and the surface morphology [2]. In most studies this problem is resolved by deconvoluting the image to obtain the true surface morphology. Although deconvolution routines work reasonably well for simple one- dimensional shapes, for complex surfaces this approach does not produce accurate results. In this study we devised a new approach which takes advantage of the precise molecular order of crystal surfaces, combined with the knowledge of individual molecular shapes from the crystallographic data of the protein and the AFM tip shape. This information is used to construct expected theoretical AFM images by convoluting the tip shape with the constructed crystal surface shape for a given surface packing arrangement. By comparing the images from actual AFM scans with the constructed ones for different possible surface packing arrangements, the correct packing arrangement can be conclusively determined. This approach was used in this study to determine the correct one from two possible packing arrangements on (I 10) faces of tetragonal lysozyme crystals. Another novel AFM technique was also devised to measure the dimension of individual growth units of the crystal faces

  4. Phase-transition properties of glycerol-dipalmitate lipid bilayers investigated using molecular dynamics simulation.

    PubMed

    Laner, Monika; Hünenberger, Philippe H

    2015-06-01

    The phase- and phase-transition properties of glycerol-dipalmitate (GDP) bilayer patches are investigated using molecular dynamics simulations. This permits to characterize the influence of introducing a second aliphatic lipid tail by comparison to previously reported simulations of glycerol-1-monopalmitate (GMP). To this purpose, a set of 67 simulations (up to 300ns duration) of 2×8×8GDP bilayer patches are performed, considering the two GDP isomers glycerol-1,3-dipalmitate (13GDP) and glycerol-1,2-dipalmitate (12GDP; racemic), two hydration levels (12GDP only), and temperatures in the range 250-370K. In agreement with experiment, the GDP simulations reveal an increase in the main transition temperature by about 25K relative to GMP, and the occurrence of non-bilayer phases at high temperatures (inverted-cylinder or stacked phases). Structurally, the GDP system tends to evidence a tighter packing of the chains, a reduced extent of tilting, increased order parameters and a reduced fluidity. These differences are easily interpreted in terms of two key changes in molecular properties when going from GMP to GDP: (i) the reduction of the headgroup polarity and hydration (from two free hydroxyl groups to a single one); (ii) the increase in the effective tail cross-section relative to the (hydrated) headgroup cross-section, conferring to GDP a particular wedge shape. These two effects contribute to the relative instability of the liquid-crystalline phase, the stability being recovered in nature when the diglyceride headgroup is functionalized by a bulky or/and polar substituent.

  5. Investigating carbon dynamics in Siberian peat bogs using molecular-level analyses

    NASA Astrophysics Data System (ADS)

    Kaiser, K.; Benner, R. H.

    2013-12-01

    Total hydrolysable carbohydrates, and lignin and cutin acid compounds were analyzed in peat cores collected 56.8 N (SIB04), 58.4 N (SIB06), 63.8 N (G137) and 66.5 N (E113) in the Western Siberian Lowland to investigate vegetation, chemical compositions and the stage of decomposition. Sphagnum mosses dominated peatland vegetation in all four cores. High-resolution molecular analyses revealed rapid vegetation changes on timescales of 50-200 years in the southern cores Sib4 and Sib6. Syringyl and vanillyl (S/V) ratios and cutin acids indicated these vegetation changes were due to varying inputs of angiosperm and gymnosperm and root material. In the G137 and E113 cores lichens briefly replaced sphagnum mosses and vascular plants. Molecular decomposition indicators used in this study tracked the decomposition of different organic constituents of peat organic matter. The carbohydrate decomposition index was sensitive to the polysaccharide component of all peat-forming plants, whereas acid/aldehyde ratios of S and V phenols (Ac/AlS,V) followed the lignin component of vascular plants. Low carbohydrate decomposition indices in peat layers corresponded well with elevated (Ad/Al)S,V ratios. This suggested both classes of biochemicals were simultaneously decomposed, and decomposition processes were associated with extensive total mass loss in these ombrotrophic systems. Selective decomposition or transformation of lignin was observed in the permafrost-influenced northern cores G137 and E113. Both cores exhibited the highest (Ad/Al)S,V ratios, almost four-fold higher than measured in peat-forming plants. The extent of decomposition in the four peat cores did not uniformly increase with age, but showed episodic extensive decomposition events. Variable decomposition events independent of climatic conditions and vegetation shifts highlight the complexity of peatland dynamics.

  6. Molecular dynamics investigations of BioH protein substrate specificity for biotin synthesis.

    PubMed

    Xue, Qiao; Cui, Ying-Lu; Zheng, Qing-Chuan; Zhang, Hong-Xing

    2016-05-01

    BioH, an enzyme of biotin synthesis, plays an important role in fatty acid synthesis which assembles the pimelate moiety. Pimeloyl-acyl carrier protein (ACP) methyl ester, which is long known to be a biotin precursor, is the physiological substrate of BioH. Azelayl methyl ester, which has a longer chain than pimeloyl methyl ester, conjugated to ACP is also indeed accepted by BioH with very low rate of hydrolysis. To date, the substrate specificity for BioH and the molecular origin for the experimentally observed rate changes of hydrolysis by the chain elongation have remained elusive. To this end, we have investigated chain elongation effects on the structures by using the fully atomistic molecular dynamics simulations combined with binding free energy calculations. The results indicate that the substrate specificity is determined by BioH together with ACP. The added two methylenes would increase the structural flexibility by protein motions at the interface of ACP and BioH, instead of making steric clashes with the side chains of the BioH hydrophobic cavity. On the other hand, the slower hydrolysis of azelayl substrate is suggested to be associated with the loose of contacts between BioH and ACP, and with the lost electrostatic interactions of two ionic/hydrogen bonding networks at the interface of the two proteins. The present study provides important insights into the structure-function relationships of the complex of BioH with pimeloyl-ACP methyl ester, which could contribute to further understanding about the mechanism of the biotin synthetic pathway, including the catalytic role of BioH.

  7. Molecular Investigation of Transmission of Human Immunodeficiency Virus Type 1 in a Criminal Case

    PubMed Central

    Machuca, Roberto; Jørgensen, Louise B.; Theilade, Peter; Nielsen, Claus

    2001-01-01

    Very few criminal cases involving human immunodeficiency virus type 1 (HIV-1) transmission have been described. We report on an HIV-1 transmission case with a child being infected by an HIV-1-positive man. The objective was to determine through molecular epidemiology and phylogenetic analyses whether HIV-1 from the HIV-1-positive man could be the source of infection in the HIV-1-positive child, as claimed by the authorities. We conducted genetic analysis of three different parts of the HIV-1 genome (gag, pol, and env) by PCR, direct-sequencing, and phylogenetic analyses. We used maximum likelihood, maximum parsimony, and neighbor-joining methods for the phylogenetic analyses to investigate whether the sequences from the man and the child were related. We found that the viral sequences from the man and the child formed separate clusters in all of the phylogenetic analyses compared to the local controls. A unique amino acid deletion was identified in the C2-V3-C3 region of the env gene in the virus from the man and the child. These results were used in the criminal court to elucidate whether the virus from the man was related to the virus from the child. In summary, the results from the phylogenetic analyses, the sequence distances between the virus from the man and the virus from the child, and the identification of the unique molecular fingerprint in the env gene together indicated that the virus from the man and the virus from the child were epidemiologically linked. PMID:11527797

  8. Molecular line emission models of Herbig-Haro objects. II - HCO(+) emission

    NASA Technical Reports Server (NTRS)

    Wolfire, Mark G.; Koenigl, Arieh

    1993-01-01

    We present time-dependent models of the chemistry and temperature of interstellar molecular gas clumps that are exposed to the radiation from propagating stellar-jet shocks. The X-ray, EUV, and FUV radiation from the shock initiates ion chemistry and also heats the gas in the clumps. Using representative parameters, we show that, on the shock transit time between the clumps, the abundances of the ionized molecular species that are produced in the clumps can exceed the values determined from steady state models by several orders of magnitude. Collisional excitation by the heated gas can lead to measurable line emission from several ionized species; as in previous investigations of X-ray-irradiated molecular gas, we find that electron impacts contribute significantly to this process. We apply these results to the interpretation of the HCO(+) line emission that has already been detected in several Herbig-Haro objects. We demonstrate that this picture provides a natural explanation of the fact that the line intensity typically peaks ahead of the associated shock, as well as of the reported low line-center velocities and narrow line widths. We tabulate several diagnostic line intensities of HCO(+) and other molecular species that may be used to infer the physical conditions in the emitting gas.

  9. Investigation of mechanisms and molecular epidemiology of linezolid nonsusceptible Enterococcus faecalis isolated from a teaching hospital in China.

    PubMed

    Li, Bin; Ma, Chuan-Ling; Yu, Xiao; Sun, Yao; Li, Mei-Mei; Ye, Jian-Zhong; Zhang, Ya-Pei; Wu, Qing; Zhou, Tie-Li

    2016-08-01

    The epidemiological and molecular characteristics of eight linezolid nonsusceptible Enterococcus faecalis isolated from a teaching hospital in China (January to July 2014) were investigated. The target site modifications and cfr gene associated with linezolid resistance were not found. Results of the epidemiological investigation indicated that linezolid resistance possibly occurred on several independent occasions and was often not related to linezolid administration.

  10. The application of molecular modelling in the safety assessment of chemicals: A case study on ligand-dependent PPARγ dysregulation.

    PubMed

    Al Sharif, Merilin; Tsakovska, Ivanka; Pajeva, Ilza; Alov, Petko; Fioravanzo, Elena; Bassan, Arianna; Kovarich, Simona; Yang, Chihae; Mostrag-Szlichtyng, Aleksandra; Vitcheva, Vessela; Worth, Andrew P; Richarz, Andrea-N; Cronin, Mark T D

    2016-02-04

    The aim of this paper was to provide a proof of concept demonstrating that molecular modelling methodologies can be employed as a part of an integrated strategy to support toxicity prediction consistent with the mode of action/adverse outcome pathway (MoA/AOP) framework. To illustrate the role of molecular modelling in predictive toxicology, a case study was undertaken in which molecular modelling methodologies were employed to predict the activation of the peroxisome proliferator-activated nuclear receptor γ (PPARγ) as a potential molecular initiating event (MIE) for liver steatosis. A stepwise procedure combining different in silico approaches (virtual screening based on docking and pharmacophore filtering, and molecular field analysis) was developed to screen for PPARγ full agonists and to predict their transactivation activity (EC50). The performance metrics of the classification model to predict PPARγ full agonists were balanced accuracy=81%, sensitivity=85% and specificity=76%. The 3D QSAR model developed to predict EC50 of PPARγ full agonists had the following statistical parameters: q(2)cv=0.610, Nopt=7, SEPcv=0.505, r(2)pr=0.552. To support the linkage of PPARγ agonism predictions to prosteatotic potential, molecular modelling was combined with independently performed mechanistic mining of available in vivo toxicity data followed by ToxPrint chemotypes analysis. The approaches investigated demonstrated a potential to predict the MIE, to facilitate the process of MoA/AOP elaboration, to increase the scientific confidence in AOP, and to become a basis for 3D chemotype development.

  11. Multi-scale modelling of supercapacitors: From molecular simulations to a transmission line model

    NASA Astrophysics Data System (ADS)

    Pean, C.; Rotenberg, B.; Simon, P.; Salanne, M.

    2016-09-01

    We perform molecular dynamics simulations of a typical nanoporous-carbon based supercapacitor. The organic electrolyte consists in 1-ethyl-3-methylimidazolium and hexafluorophosphate ions dissolved in acetonitrile. We simulate systems at equilibrium, for various applied voltages. This allows us to determine the relevant thermodynamic (capacitance) and transport (in-pore resistivities) properties. These quantities are then injected in a transmission line model for testing its ability to predict the charging properties of the device. The results from this macroscopic model are in good agreement with non-equilibrium molecular dynamics simulations, which validates its use for interpreting electrochemical impedance experiments.

  12. Molecular modeling of various peptide sequences of gliadins and low-molecular-weight glutenin subunits.

    PubMed

    Yaşar, Fatih; Celik, Süeda; Köksel, Hamit

    2003-08-01

    The contribution of the three-dimensional structures of one heptapeptide (PQPQPFP) sequence and one pentapeptide (PQQPY) repeat sequence of alpha/beta-gliadins, one heptapeptide (PQQPFPQ) repeat sequence of gamma-gliadins, two heptapeptide (PQQPPFS and QQQQPVL) repeat motifs of low-molecular-weight (LMW) subunits and a tetrapeptide sequence in polyQ region of S-rich prolamins to their conformations are investigated by using the recently developed multicanonical simulation procedure. Ramachandran plots were prepared and analysed to predict the relative occurrence probabilities of gamma-tutn, gamma-turn, and helical structures. The probability of inverse 7-turn was generally higher than that of beta-turns in all sequences investigated. Occurrence probability of helical structure in the repetitive domain of gliadins was low. Structural predictions of QQQQPVL sequence of LMW-glutenin subunits and QQQQ sequence in the polyQ region of S-rich prolamins indicate the presence of helical structures with the probability of >20%. The probability of helical structure significantly decreased around 100 degrees C.

  13. Model morphing and sequence assignment after molecular replacement.

    PubMed

    Terwilliger, Thomas C; Read, Randy J; Adams, Paul D; Brunger, Axel T; Afonine, Pavel V; Hung, Li-Wei

    2013-11-01

    A procedure termed `morphing' for improving a model after it has been placed in the crystallographic cell by molecular replacement has recently been developed. Morphing consists of applying a smooth deformation to a model to make it match an electron-density map more closely. Morphing does not change the identities of the residues in the chain, only their coordinates. Consequently, if the true structure differs from the working model by containing different residues, these differences cannot be corrected by morphing. Here, a procedure that helps to address this limitation is described. The goal of the procedure is to obtain a relatively complete model that has accurate main-chain atomic positions and residues that are correctly assigned to the sequence. Residues in a morphed model that do not match the electron-density map are removed. Each segment of the resulting trimmed morphed model is then assigned to the sequence of the molecule using information about the connectivity of the chains from the working model and from connections that can be identified from the electron-density map. The procedure was tested by application to a recently determined structure at a resolution of 3.2 Å and was found to increase the number of correctly identified residues in this structure from the 88 obtained using phenix.resolve sequence assignment alone (Terwilliger, 2003) to 247 of a possible 359. Additionally, the procedure was tested by application to a series of templates with sequence identities to a target structure ranging between 7 and 36%. The mean fraction of correctly identified residues in these cases was increased from 33% using phenix.resolve sequence assignment to 47% using the current procedure. The procedure is simple to apply and is available in the Phenix software package.

  14. Real-time investigation of nucleic acids phosphorylation process using molecular beacons

    PubMed Central

    Tang, Zhiwen; Wang, Kemin; Tan, Weihong; Ma, Changbei; Li, Jun; Liu, Lingfeng; Guo, Qiuping; Meng, Xiangxian

    2005-01-01

    Phosphorylation of nucleic acids is an indispensable process to repair strand interruption of nucleic acids. We have studied the process of phosphorylation using molecular beacon (MB) DNA probes in real-time and with high selectivity. The MB employed in this method is devised to sense the product of a ‘phosphorylation–ligation’ coupled enzyme reaction. Compared with the current assays, this novel method is convenient, fast, selective, highly sensitive and capable of real-time monitoring in a homogenous solution. The preference of T4 polynucleotide kinase (T4 PNK) has been investigated using this approach. The results revealed that a single-stranded oligonucleotide containing guanine at the 5′ termini is most preferred, while those utilizing cytosine in this location are least preferred. The preference of (T)9 was reduced greatly when phosphoryl was modified at the 5′ end, implying that T4 PNK could discern the phosphorylated/unphosphorylated oligonucleotides. The increase of oligonucleotide DNA length leads to an enhancement in preference. A fast and accurate method for assaying the kinase activity of T4 PNK has been developed with a wide linear detection range from 0.002 to 4.0 U/ml in 3 min. The effects of certain factors, such as NTP, ADP, (NH4)2SO4 and Na2HPO4, on phosphorylation have been investigated. This novel approach enables us to investigate the interactions between proteins and nucleic acids in a homogenous solution, such as those found in DNA repair or in drug development. PMID:15961728

  15. Molecular Dynamics Investigations of the Ablator/Fuel Interface during Early Stages of Inertial Confinement Fusion

    NASA Astrophysics Data System (ADS)

    Stanton, Liam; Glosli, James; Murillo, Michael

    2016-10-01

    At the National Ignition Facility, high-powered laser beams are used to compress a small target to generate fusion reactions. A critical issue in achieving this is the understanding of mix at the ablator/fuel interface. Mixing occurs at various length scales, ranging from atomic inter-species diffusion to hydrodynamic instabilities. Because the interface is preheated by energy from the incoming shock, it is important to understand the dynamics before the shock arrives. The interface is in the warm dense matter phase with a deuterium/tritium fuel mixture on one side and a plastic mixture on the other. We would like to understand various aspects of the evolution, including the state of the interface when the main shock arrives, the role of electric field generation at the interface, and the character and time scales for diffusion. We present a multiscale approach to model these processes, which combines molecular dynamics to simulate the ionic degrees of freedom with orbital-free density functional theory to calculate the electronic structure. Simulation results are presented and connections to hydrodynamic models are discussed. This work is performed under the auspices of the U. S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  16. Mechanical Properties of Nanostructured Materials Determined Through Molecular Modeling Techniques

    NASA Technical Reports Server (NTRS)

    Clancy, Thomas C.; Gates, Thomas S.

    2005-01-01

    The potential for gains in material properties over conventional materials has motivated an effort to develop novel nanostructured materials for aerospace applications. These novel materials typically consist of a polymer matrix reinforced with particles on the nanometer length scale. In this study, molecular modeling is used to construct fully atomistic models of a carbon nanotube embedded in an epoxy polymer matrix. Functionalization of the nanotube which consists of the introduction of direct chemical bonding between the polymer matrix and the nanotube, hence providing a load transfer mechanism, is systematically varied. The relative effectiveness of functionalization in a nanostructured material may depend on a variety of factors related to the details of the chemical bonding and the polymer structure at the nanotube-polymer interface. The objective of this modeling is to determine what influence the details of functionalization of the carbon nanotube with the polymer matrix has on the resulting mechanical properties. By considering a range of degree of functionalization, the structure-property relationships of these materials is examined and mechanical properties of these models are calculated using standard techniques.

  17. Bayesian molecular design with a chemical language model.

    PubMed

    Ikebata, Hisaki; Hongo, Kenta; Isomura, Tetsu; Maezono, Ryo; Yoshida, Ryo

    2017-03-09

    The aim of computational molecular design is the identification of promising hypothetical molecules with a predefined set of desired properties. We address the issue of accelerating the material discovery with state-of-the-art machine learning techniques. The method involves two different types of prediction; the forward and backward predictions. The objective of the forward prediction is to create a set of machine learning models on various properties of a given molecule. Inverting the trained forward models through Bayes' law, we derive a posterior distribution for the backward prediction, which is conditioned by a desired property requirement. Exploring high-probability regions of the posterior with a sequential Monte Carlo technique, molecules that exhibit the desired properties can computationally be created. One major difficulty in the computational creation of molecules is the exclusion of the occurrence of chemically unfavorable structures. To circumvent this issue, we derive a chemical language model that acquires commonly occurring patterns of chemical fragments through natural language processing of ASCII strings of existing compounds, which follow the SMILES chemical language notation. In the backward prediction, the trained language model is used to refine chemical strings such that the properties of the resulting structures fall within the desired property region while chemically unfavorable structures are successfully removed. The present method is demonstrated through the design of small organic molecules with the property requirements on HOMO-LUMO gap and internal energy. The R package iqspr is available at the CRAN repository.

  18. Bayesian molecular design with a chemical language model

    NASA Astrophysics Data System (ADS)

    Ikebata, Hisaki; Hongo, Kenta; Isomura, Tetsu; Maezono, Ryo; Yoshida, Ryo

    2017-03-01

    The aim of computational molecular design is the identification of promising hypothetical molecules with a predefined set of desired properties. We address the issue of accelerating the material discovery with state-of-the-art machine learning techniques. The method involves two different types of prediction; the forward and backward predictions. The objective of the forward prediction is to create a set of machine learning models on various properties of a given molecule. Inverting the trained forward models through Bayes' law, we derive a posterior distribution for the backward prediction, which is conditioned by a desired property requirement. Exploring high-probability regions of the posterior with a sequential Monte Carlo technique, molecules that exhibit the desired properties can computationally be created. One major difficulty in the computational creation of molecules is the exclusion of the occurrence of chemically unfavorable structures. To circumvent this issue, we derive a chemical language model that acquires commonly occurring patterns of chemical fragments through natural language processing of ASCII strings of existing compounds, which follow the SMILES chemical language notation. In the backward prediction, the trained language model is used to refine chemical strings such that the properties of the resulting structures fall within the desired property region while chemically unfavorable structures are successfully removed. The present method is demonstrated through the design of small organic molecules with the property requirements on HOMO-LUMO gap and internal energy. The R package iqspr is available at the CRAN repository.

  19. Multiscale modeling for materials design: Molecular square catalysts

    NASA Astrophysics Data System (ADS)

    Majumder, Debarshi

    In a wide variety of materials, including a number of heterogeneous catalysts, the properties manifested at the process scale are a consequence of phenomena that occur at different time and length scales. Recent experimental developments allow materials to be designed precisely at the nanometer scale. However, the optimum design of such materials requires capabilities to predict the properties at the process scale based on the phenomena occurring at the relevant scales. The thesis research reported here addresses this need to develop multiscale modeling strategies for the design of new materials. As a model system, a new system of materials called molecular squares was studied in this research. Both serial and parallel multiscale strategies and their components were developed as parts of this work. As a serial component, a parameter estimation tool was developed that uses a hierarchical protocol and consists of two different search elements: a global search method implemented using a genetic algorithm that is capable of exploring large parametric space, and a local search method using gradient search techniques that accurately finds the optimum in a localized space. As an essential component of parallel multiscale modeling, different standard as well as specialized computational fluid dynamics (CFD) techniques were explored and developed in order to identify a technique that is best suited to solve a membrane reactor model employing layered films of molecular squares as the heterogeneous catalyst. The coupled set of non-linear partial differential equations (PDEs) representing the continuum model was solved numerically using three different classes of methods: a split-step method using finite difference (FD); domain decomposition in two different forms, one involving three overlapping subdomains and the other involving a gap-tooth scheme; and the multiple-timestep method that was developed in this research. The parallel multiscale approach coupled continuum

  20. Stereoselective synthesis and molecular modeling of chiral cyclopentanes.

    PubMed

    Abdel-Jalil, Raid J; Steinbrecher, Thomas; Al-Harthy, Thuraya; Mahal, Ahmed; Abou-Zied, Osama K; Voelter, Wolfgang

    2015-10-13

    The reaction of 3-methyseleno-2-methylselenomethyl-propene with benzyl 2,3-anhydro-4-O-triflyl-β-L-ribopyranoside provides a major convenient enantiomeric product of 1-methylene-(benzyl3,4-dideoxy-α-D-arabinopyranoso)-[3,4-c]-cyclopentane, with benzyl-2,3-anhydro-4-deoxy-4-C-(2-methyl- propen-3-yl)-α-D-lyxopyranoside as a minor product. While the reaction of 3-methyseleno-2-[methylselenomethyl]-propene with benzyl 2,3-anhydro-4-O-triflyl-α-D-ribopyranoside produces a good yield of benzyl-2,3-anhydro-4-deoxy-4-C-(2-methylpropen-3-yl)-α-D-lyxo-pyranoside. Molecular modeling and molecular dynamics simulations indicate that the intermediate in the reaction of the β-L sugar frequently occupies an optimal conformation that leads to the formation of cyclopentane, while the intermediate in the reaction of the α-D sugar has a very small probability. The results point to the dominant role of the β-L sugar intermediate in controlling the cyclopentane formation.