Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3039

Search results for: molecular interactions

3039 Dissociation of Hydrophobic Interactions in Whey Protein Polymers: Molecular Characterization Using Dilute Solution Viscometry

Authors: Ahmed S. Eissa


Whey represents about 85-95% of the milk volume and about 55% of milk nutrients. Whey proteins are of special importance in formulated foods due to their rich nutritional and functional benefits. Whey proteins form large polymers upon heating to a temperature greater than the denaturation temperature. Hydrophobic interactions play an important role in building whey protein polymers. In this study, dissociation of hydrophobic interactions of whey protein polymers was done by adding Sodium Dodecyl Sulphonate (SDS). At low SDS concentrations, protein polymers were dissociated to smaller chains, as revealed by dilution solution viscometry (DSV). Interestingly, at higher SDS concentrations, polymer molecules got larger in size. Intrinsic viscosity was increased to many folds when raising the SDS concentration from 0.5% to 2%. Complex molecular arrangement leads to the formation of larger macromolecules, due to micelle formation. The study opens a venue for manipulating and enhancing whey protein functional properties by manipulating the hydrophobic interactions.

Keywords: whey proteins, hydrophobic interactions, SDS

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3038 Lifestyle Switching Phenomenon of Plant Associated Fungi

Authors: Gauravi Agarkar, Mahendra Rai


Fungi are closely associated with the plants in various types of interactions such as mycorrhizal, parasitic or endophytic. Some of these interactions are beneficial and a few are harmful to the host plants. It has been suggested that these plant-associated fungi are able to change their lifestyle abd this means endophyte may become parasite or vice versa. This phenomenon may have profound effect on plant-fungal interactions and various ecological niches. Therefore, it is necessary to identify the factors that trigger the change in fungal lifestyle and understand whether these different lifestyles are interconnected at some points either by physiological, biochemical or molecular routes. This review summarizes the factors affecting plant fungal interactions and discusses the possible mechanisms for lifestyles switching of fungi based on available experimental evidences. Research should be boosted in this direction to fetch more advantages in future and to avoid the severe consequences in agriculture and other related fields.

Keywords: endophytic, lifestyle switching, mycorrhizal, parasitic, plant-fungal interactions

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3037 Effects of Twitter Interactions on Self-Esteem and Narcissistic Behaviour

Authors: Leena-Maria Alyedreessy


Self-esteem is thought to be determined by ones’ own feeling of being included, liked and accepted by others. This research explores whether this concept may also be applied in the virtual world and assesses whether there is any relationship between Twitter users' self-esteem and the amount of interactions they receive. 20 female Arab participants were given a survey asking them about their Twitter interactions and their feelings of having an imagined audience to fill out and a Rosenberg Self-Esteem Assessment to complete. After completion and statistical analysis, results showed a significant correlation between the feeling of being Twitter elite, the feeling of having a lot of people listening to your tweets and having a lot of interactions with high self-esteem. However, no correlations were detected for low-self-esteem and low interactions.

Keywords: twitter, social media, self-esteem, narcissism, interactions

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3036 Determination of Biomolecular Interactions Using Microscale Thermophoresis

Authors: Lynn Lehmann, Dinorah Leyva, Ana Lazic, Stefan Duhr, Philipp Baaske


Characterization of biomolecular interactions, such as protein-protein, protein-nucleic acid or protein-small molecule, provides critical insights into cellular processes and is essential for the development of drug diagnostics and therapeutics. Here we present a novel, label-free, and tether-free technology to analyze picomolar to millimolar affinities of biomolecular interactions by Microscale Thermophoresis (MST). The entropy of the hydration shell surrounding molecules determines thermophoretic movement. MST exploits this principle by measuring interactions using optically generated temperature gradients. MST detects changes in the size, charge and hydration shell of molecules and measures biomolecule interactions under close-to-native conditions: immobilization-free and in bioliquids of choice, including cell lysates and blood serum. Thus, MST measures interactions under close-to-native conditions, and without laborious sample purification. We demonstrate how MST determines the picomolar affinities of antibody::antigen interactions, and protein::protein interactions measured from directly from cell lysates. MST assays are highly adaptable to fit to the diverse requirements of different and complex biomolecules. NanoTemper´s unique technology is ideal for studies requiring flexibility and sensitivity at the experimental scale, making MST suitable for basic research investigations and pharmaceutical applications.

Keywords: biochemistry, biophysics, molecular interactions, quantitative techniques

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3035 Surface Sensing of Atomic Behavior of Polymer Nanofilms via Molecular Dynamics Simulation

Authors: Ling Dai


Surface-sensing devices such as atomic force microscope have been widely used to characterize the surface structure and properties of nanoscale polymer films. However, using molecular dynamics simulations, we show that there is intrinsic and unavoidable inelastic deformation at polymer surfaces induced by the sensing tip. For linear chain polymers like perfluoropolyether, such tip-induced deformation derives from the differences in the atomic interactions which are atomic specie-based Van der Waals interactions, and resulting in atomic shuffling and causing inelastic alternation in both molecular structures and mechanical properties at the regions of the polymer surface. For those aromatic chain polymers like epoxy, the intrinsic deformation is depicted as the intra-chain rotation of aromatic rings and kinking of linear atomic connections. The present work highlights the need to reinterpret the data obtained from surface-sensing tests by considering this intrinsic inelastic deformation occurring at polymer surfaces.

Keywords: polymer, surface, nano, molecular dynamics

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3034 Molecular Docking Assessment of Pesticides Binding to Bacterial Chitinases

Authors: Diana Larisa Vladoiu, Vasile Ostafe, Adriana Isvoran


Molecular docking calculations reveal that pesticides provide favorable interactions with the bacterial chitinases. Pesticides interact with both hydrophilic and aromatic residues involved in the active site of the enzymes, their positions partially overlapping the substrate and the inhibitors locations. Molecular docking outcomes, in correlation with experimental literature data, suggest that the pesticides may be degraded or having an inhibitor effect on the activity of these enzymes, depending of the application dose and rate.

Keywords: chitinases, inhibition, molecular docking, pesticides

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3033 Applying Computer Simulation Methods to a Molecular Understanding of Flaviviruses Proteins towards Differential Serological Diagnostics and Therapeutic Intervention

Authors: Sergio Alejandro Cuevas, Catherine Etchebest, Fernando Luis Barroso Da Silva


The flavivirus genus has several organisms responsible for generating various diseases in humans. Special in Brazil, Zika (ZIKV), Dengue (DENV) and Yellow Fever (YFV) viruses have raised great health concerns due to the high number of cases affecting the area during the last years. Diagnostic is still a difficult issue since the clinical symptoms are highly similar. The understanding of their common structural/dynamical and biomolecular interactions features and differences might suggest alternative strategies towards differential serological diagnostics and therapeutic intervention. Due to their immunogenicity, the primary focus of this study was on the ZIKV, DENV and YFV non-structural proteins 1 (NS1) protein. By means of computational studies, we calculated the main physical chemical properties of this protein from different strains that are directly responsible for the biomolecular interactions and, therefore, can be related to the differential infectivity of the strains. We also mapped the electrostatic differences at both the sequence and structural levels for the strains from Uganda to Brazil that could suggest possible molecular mechanisms for the increase of the virulence of ZIKV. It is interesting to note that despite the small changes in the protein sequence due to the high sequence identity among the studied strains, the electrostatic properties are strongly impacted by the pH which also impact on their biomolecular interactions with partners and, consequently, the molecular viral biology. African and Asian strains are distinguishable. Exploring the interfaces used by NS1 to self-associate in different oligomeric states, and to interact with membranes and the antibody, we could map the strategy used by the ZIKV during its evolutionary process. This indicates possible molecular mechanisms that can explain the different immunological response. By the comparison with the known antibody structure available for the West Nile virus, we demonstrated that the antibody would have difficulties to neutralize the NS1 from the Brazilian strain. The present study also opens up perspectives to computationally design high specificity antibodies.

Keywords: zika, biomolecular interactions, electrostatic interactions, molecular mechanisms

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3032 Spectrofluorometric Studies on the Interactions of Bovine Serum Albumin with Dimeric Cationic Surfactants

Authors: Srishti Sinha, Deepti Tikariha, Kallol K. Ghosh


Over the past few decades protein-surfactant interactions have been a subject of extensive studies as they are of great importance in wide variety of industries, biological, pharmaceutical and cosmetic systems. Protein-surfactant interactions have been explored the effect of surfactants on structure of protein in the form of solubilization and denaturing or renaturing of protein. Globular proteins are frequently used as functional ingredients in healthcare and pharmaceutical products, due to their ability to catalyze biochemical reactions, to be adsorbed on the surface of some substance and to bind other moieties and form molecular aggregates. One of the most widely used globular protein is bovine serum albumin (BSA), since it has a well-known primary structure and been associated with the binding of many different categories of molecules, such as dyes, drugs and toxic chemicals. Protein−surfactant interactions are usually dependent on the surfactant features. Most of the research has been focused on single-chain surfactants. More recently, the binding between proteins and dimeric surfactants has been discussed. In present study interactions of one dimeric surfactant Butanediyl-1,4-bis (dimethylhexadecylammonium bromide) (16-4-16, 2Br-) and the corresponding single-chain surfactant cetyl trimethylammonium bromide (CTAB) with bovine serum albumin (BSA) have been investigated by surface tension and spectrofluoremetric methods. It has been found that the bindings of all gemini surfactant to BSA were cooperatively driven by electrostatic and hydrophobic interactions. The gemini surfactant carrying more charges and hydrophobic tails, showed stronger interactions with BSA than the single-chain surfactant.

Keywords: bovine serum albumin, gemini surfactants, hydrophobic interactions, protein surfactant interaction

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3031 DFT Study of Hoogsteen-Type Base Pairs

Authors: N. Amraoui, D. Hammoutene


We have performed a theoretical study using dispersion-corrected Density Functional Methods to evaluate a variety of artificial nucleobases as candidates for metal-mediated Hoogsteen-type base pairs. We focus on A-M-T Hoogsteen-type base pair with M=Co(II), Ru(I), Ni(I). All calculations are performed using (ADF 09) program. Metal-mediated Hoogsteen-type base pairs are studied as drug candidates, their geometry optimizations are performed at ZORA/TZ2P/BLYP-D level. The molecular geometries and different energies as total energies, coordination energies, Pauli interactions, orbital interactions and electrostatic energies are determined.

Keywords: chemistry, biology, density functional method, orbital interactions

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3030 Investigations of Inclusion Complexes of Imazapyr with 2-Hydroxypropyl(β/γ) Cyclodextrin Experimental and Molecular Modeling Approach

Authors: Abdalla A. Elbashir, Maali Saad Mokhtar, FakhrEldin O. Suliman


The inclusion complexes of imazapyr (IMA) with 2-hydroxypropyl(β/γ) cyclodextrins (HP β/γ-CD), have been studied in aqueous media and in the solid state. In this work, fluorescence spectroscopy, electrospray-ionization mass spectrometry (ESI-MS), and HNMR were used to investigate and characterize the inclusion complexes of IMA with the cyclodextrins in solutions. The solid-state complexes were obtained by freeze-drying and were characterized by Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffraction (PXRD). The most predominant complexes of IMA with both hosts are the 1:1 guest: host complexes. The association constants of IMA-HP β-CD and IMA-HP γ -CD were 115 and 215 L mol⁻¹, respectively. Molecular dynamic (MD) simulations were used to monitor the mode of inclusion and also to investigate the stability of these complexes in aqueous media at atomistic levels. The results obtained have indicated that these inclusion complexes are highly stable in aqueous media, thereby corroborating the experimental results. Additionally, it has been demonstrated that in addition to hydrophobic interactions and van der Waals interactions the presence of hydrogen bonding interactions of the type H---O and CH---O between the guest and the host have enhanced the stability of these complexes remarkably.

Keywords: imazapyr, inclusion complex, herbicides, 2-hydroxypropyl-β/γ-cyclodextrin

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3029 Computational Approach for Grp78–Nf-ΚB Binding Interactions in the Context of Neuroprotective Pathway in Brain Injuries

Authors: Janneth Gonzalez, Marco Avila, George Barreto


GRP78 participates in multiple functions in the cell during normal and pathological conditions, controlling calcium homeostasis, protein folding and unfolded protein response. GRP78 is located in the endoplasmic reticulum, but it can change its location under stress, hypoxic and apoptotic conditions. NF-κB represents the keystone of the inflammatory process and regulates the transcription of several genes related with apoptosis, differentiation, and cell growth. The possible relationship between GRP78-NF-κB could support and explain several mechanisms that may regulate a variety of cell functions, especially following brain injuries. Although several reports show interactions between NF-κB and heat shock proteins family members, there is a lack of information on how GRP78 may be interacting with NF-κB, and possibly regulating its downstream activation. Therefore, we assessed the computational predictions of the GRP78 (Chain A) and NF-κB complex (IkB alpha and p65) protein-protein interactions. The interaction interface of the docking model showed that the amino acids ASN 47, GLU 215, GLY 403 of GRP78 and THR 54, ASN 182 and HIS 184 of NF-κB are key residues involved in the docking. The electrostatic field between GRP78-NF-κB interfaces and molecular dynamic simulations support the possible interaction between the proteins. In conclusion, this work shed some light in the possible GRP78-NF-κB complex indicating key residues in this crosstalk, which may be used as an input for better drug design strategy targeting NF-κB downstream signaling as a new therapeutic approach following brain injuries.

Keywords: computational biology, protein interactions, Grp78, bioinformatics, molecular dynamics

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3028 Development of Immuno-Modulators: Application of Molecular Dynamics Simulation

Authors: Ruqaiya Khalil, Saman Usmani, Zaheer Ul-Haq


The accurate characterization of ligand binding affinity is indispensable for designing molecules with optimized binding affinity. Computational tools help in many directions to predict quantitative correlations between protein-ligand structure and their binding affinities. Molecular dynamics (MD) simulation is a modern state-of-the-art technique to evaluate the underlying basis of ligand-protein interactions by characterizing dynamic and energetic properties during the event. Autoimmune diseases arise from an abnormal immune response of the body against own tissues. The current regimen for the described condition is limited to immune-modulators having compromised pharmacodynamics and pharmacokinetics profiles. One of the key player mediating immunity and tolerance, thus invoking autoimmunity is Interleukin-2; a cytokine influencing the growth of T cells. Molecular dynamics simulation techniques are applied to seek insight into the inhibitory mechanisms of newly synthesized compounds that manifested immunosuppressant potentials during in silico pipeline. In addition to estimation of free energies associated with ligand binding, MD simulation yielded us a great deal of information about ligand-macromolecule interactions to evaluate the pattern of interactions and the molecular basis of inhibition. The present study is a continuum of our efforts to identify interleukin-2 inhibitors of both natural and synthetic origin. Herein, we report molecular dynamics simulation studies of Interluekin-2 complexed with different antagonists previously reported by our group. The study of protein-ligand dynamics enabled us to gain a better understanding of the contribution of different active site residues in ligand binding. The results of the study will be used as the guide to rationalize the fragment based synthesis of drug-like interleukin-2 inhibitors as immune-modulators.

Keywords: immuno-modulators, MD simulation, protein-ligand interaction, structure-based drug design

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3027 Insights into Insect Vectors: Liberibacter Interactions

Authors: Murad Ghanim


The citrus greening disease, also known as Huanglongbing, caused by the phloem-limited bacterium Candidatus Liberibacter asiaticus (CLas) has resulted in tremendous losses and the death of millions of citrus trees worldwide. CLas is transmitted by the Asian citrus psyllid (ACP) Diaphorina citri. The closely-related bacterium Candidatus Liberibacter solanacearum (CLso), which is associated with vegetative disorders in carrots and the zebra chips disease in potatoes, is transmitted by other psyllid species including Bactericera trigonica in carrots and B. ckockerelli in potatoes. Chemical sprays are currently the prevailing method for managing these diseases for limiting psyllid populations; however, they are limited in their effectiveness. A promising approach to prevent the transmission of these pathogens is to interfere with the vector-pathogen interactions, but our understanding of these processes is very limited. CLas induces changes in the nuclear architecture in the midgut of ACP and activates programmed cell death (apoptosis) in this organ. Strikingly, CLso displayed an opposite effect in the gut of B. trigonica, showing limited apoptosis, but widespread necrosis. Electron and fluorescent microscopy further showed that CLas induced the formation of Endoplasmic reticulum (ER) inclusion- and replication-like bodies, in which it increases and multiplies. ER involvement in bacterial replication is hypothesized to be the first stage of an immune response leading to the apoptotic and necrotic responses. ER exploitation and the subsequent events that lead to these cellular and stress responses might activate a cascade of molecular responses ending up with apoptosis and necrosis. Understanding the molecular interactions that underlay the necrotic/apoptotic responses to the bacteria will increase our knowledge of ACP-CLas, and BT-CLso interactions, and will set the foundation for developing novel, and efficient strategies to disturb these interactions and inhibit the transmission.

Keywords: Liberibacter, psyllid, transmission, apoptosis, necrosis

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3026 Synthesis, Structural, Spectroscopic and Nonlinear Optical Properties of New Picolinate Complex of Manganese (II) Ion

Authors: Ömer Tamer, Davut Avcı, Yusuf Atalay


Novel picolinate complex of manganese(II) ion, [Mn(pic)2] [pic: picolinate or 2-pyridinecarboxylate], was prepared and fully characterized by single crystal X-ray structure determination. The manganese(II) complex was characterized by FT-IR, FT-Raman and UV–Vis spectroscopic techniques. The C=O, C=N and C=C stretching vibrations were found to be strong and simultaneously active in IR and spectra. In order to support these experimental techniques, density functional theory (DFT) calculations were performed at Gaussian 09W. Although the supramolecular interactions have some influences on the molecular geometry in solid state phase, the calculated data show that the predicted geometries can reproduce the structural parameters. The molecular modeling and calculations of IR, Raman and UV-vis spectra were performed by using DFT levels. Nonlinear optical (NLO) properties of synthesized complex were evaluated by the determining of dipole moment (µ), polarizability (α) and hyperpolarizability (β). Obtained results demonstrated that the manganese(II) complex is a good candidate for NLO material. Stability of the molecule arising from hyperconjugative interactions and charge delocalization was analyzed using natural bond orbital (NBO) analysis. The highest occupied and the lowest unoccupied molecular orbitals (HOMO and LUMO) which is also known the frontier molecular orbitals were simulated, and obtained energy gap confirmed that charge transfer occurs within manganese(II) complex. Molecular electrostatic potential (MEP) for synthesized manganese(II) complex displays the electrophilic and nucleophilic regions. From MEP, the the most negative region is located over carboxyl O atoms while positive region is located over H atoms.

Keywords: DFT, picolinate, IR, Raman, nonlinear optic

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3025 Viscoelastic Response of the Human Corneal Stroma Induced by Riboflavin/UVA Cross-Linking

Authors: C. Labate, M. P. De Santo, G. Lombardo, R. Barberi, M. Lombardo, N. M. Ziebarth


In the past decades, the importance of corneal biomechanics in the normal and pathological functions of the eye has gained its credibility. In fact, the mechanical properties of biological tissues are essential to their physiological function. We are convinced that an improved understanding of the nanomechanics of corneal tissue is important to understand the basic molecular interactions between collagen fibrils. Ultimately, this information will help in the development of new techniques to cure ocular diseases and in the development of biomimetic materials. Therefore, nanotechnology techniques are powerful tools and, in particular, Atomic Force Microscopy has demonstrated its ability to reliably characterize the biomechanics of biological tissues either at the micro- or nano-level. In the last years, we have investigated the mechanical anisotropy of the human corneal stroma at both the tissue and molecular levels. In particular, we have focused on corneal cross-linking, an established procedure aimed at slowing down or halting the progression of the disease known as keratoconus. We have obtained the first evidence that riboflavin/UV-A corneal cross-linking induces both an increase of the elastic response and a decrease of the viscous response of the most anterior stroma at the scale of stromal molecular interactions.

Keywords: atomic force spectroscopy, corneal stroma, cross-linking, viscoelasticity

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3024 Impact of New Media Technologies to News, Social Interactions, and Traditional Media

Authors: Ademola Bamgbose


The new media revolution, which encompasses a wide variety of new media technologies like blogs, social networking, visual worlds, wikis, have had a great influence on communications, traditional media and across other disciplines. This paper gives a review of the impact of new media technologies on the news, social interactions and traditional media in developing and developed countries. The study points to the fact that there is a significant impact of new media technologies on the news, social interactions and the traditional media in developing and developed countries, albeit both positively and negatively. Social interactions have been significantly affected, as well as in news production and reporting. It is reiterated that despite the pervasiveness of new media technologies, it would not bring to a total decline of traditional media. This paper contributes to the theoretical framework on the new media and will help to assess the extent of the impact of the new media in different locations.

Keywords: communication, media, news, new media technologies, social interactions, traditional media

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3023 Dialogue, Agency and Appropriation in Peer Interactions

Authors: Mohammad Naseh Nasrollahi Shahri


The article draws on Michael Bakhtin’s theory of language to examine peer interactions. It represents an analysis of other-repetition in student interactions. Several recent studies have explored various aspects of repetition in multiple contexts. However, other-repetition in peer interactions has not received enough attention. Building on previous studies, this study examines patterns of other-repetition or appropriation in the context of discussion activities performed by EFL learners. The analysis highlights the meaningfulness of other-repetition in a way that distinguishes them from rote-repetition. It is suggested that instances of repetition constitute third spaces between the self and other which provide ideal settings for language learning and demonstrate student agency and engagement.

Keywords: repetition, agency, Bakhtin, dialogue

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3022 Molecular Modeling a Tool for Postulating the Mechanism of Drug Interaction: Glimepiride Alters the Pharmacokinetics of Sildenafil Citrate in Diabetic Nephropathy Animals

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


The present study evaluates the possible drug interaction between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ) induced in diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction by molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg/kg, ip) and confirms it by assessing the blood and urine biochemical parameters on 28th day of its induction. Selected DN animals were used for the drug interaction between GLIM (0.5mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) after 29th and 70th day of protocol. Drug interaction were assessed by evaluating the plasma drug concentration using HPLC-UV and also determine the change in the biochemical parameter in blood and urine. Mechanism of the interaction was postulated by molecular modeling study using Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in the blood and urine biochemical parameter in STZ treated groups. The concentration of SIL increased significantly (p<0.001) in rat plasma when co administered with GLIM after 70th day of protocol. Molecular modelling study revealed few important interactions with rat serum albumin and CYP2C9.GLIM has strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL. Whereas, for CYP2C9, GLIM has strong hydrogen bond with polar contacts and hydrophobic interactions than SIL. Present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals and mechanism has been supported by molecular modeling studies.

Keywords: diabetic nephropathy, glimepiride, sildenafil citrate, pharmacokinetics, homology modeling, schrodinger

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3021 Membrane Permeability of Middle Molecules: A Computational Chemistry Approach

Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa


Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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3020 Understanding Inhibitory Mechanism of the Selective Inhibitors of Cdk5/p25 Complex by Molecular Modeling Studies

Authors: Amir Zeb, Shailima Rampogu, Minky Son, Ayoung Baek, Sang H. Yoon, Keun W. Lee


Neurotoxic insults activate calpain, which in turn produces truncated p25 from p35. p25 forms hyperactivated Cdk5/p25 complex, and thereby induces severe neuropathological aberrations including hyperphosphorylated tau, neuroinflammation, apoptosis, and neuronal death. Inhibition of Cdk5/p25 complex alleviates aberrant phosphorylation of tau to mitigate AD pathology. PHA-793887 and Roscovitine have been investigated as selective inhibitors of Cdk5/p25 with IC50 values 5nM and 160nM, respectively, but their mechanistic studies remain unknown. Herein, computational simulations have explored the binding mode and interaction mechanism of PHA-793887 and Roscovitine with Cdk5/p25. Docking results suggested that PHA-793887 and Rsocovitine have occupied the ATP-binding site of Cdk5 and obtained highest docking (GOLD) score of 66.54 and 84.03, respectively. Furthermore, molecular dynamics (MD) simulation demonstrated that PHA-793887 and Roscovitine established stable RMSD of 1.09 Å and 1.48 Å with Cdk5/p25, respectively. Profiling of polar interactions suggested that each inhibitor formed hydrogen bonds (H-bond) with catalytic residues of Cdk5 and could remain stable throughout the molecular dynamics simulation. Additionally, binding free energy calculation by molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) suggested that PHA-793887 and Roscovitine had lowest binding free energies of -150.05 kJ/mol and -113.14 kJ/mol, respectively with Cdk5/p25. Free energy decomposition demonstrated that polar energy by H-bond between the Glu81 of Cdk5 and PHA-793887 is the essential factor to make PHA-793887 highly selective towards Cdk5/p25. Overall, this study provided substantial evidences to explore mechanistic interactions of the selective inhibitors of Cdk5/p25 and could be used as fundamental considerations in the development of structure-based selective inhibitors of Cdk5/p25.

Keywords: Cdk5/p25 inhibition, molecular modeling of Cdk5/p25, PHA-793887 and roscovitine, selective inhibition of Cdk5/p25

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3019 Molecular Electrostatic Potential in Z-3N(2-Ethoxyphenyl), 2-N'(2-Ethoxyphenyl) Imino Thiazolidin-4-one Molecule by Ab Initio and DFT Methods

Authors: Manel Boulakoud, Abdelkader Chouaih, Fodil Hamzaoui


In the present work we are interested in the determination of the Molecular electrostatic potential (MEP) in Z-3N(2-Ethoxyphenyl), 2-N’(2-Ethoxyphenyl) imino thiazolidin-4-one molecule by ab initio and Density Functional Theory (DFT) in the ground state. The MEP is related to the electronic density and is a very useful descriptor in understanding sites for electrophilic attack and nucleophilic reactions as well as hydrogen bonding interactions. First, geometry optimization was carried out using Hartree–Fock (HF) and DFT methods with 6-311G(d,p) basis set. In order to get more information on the molecule, its stability has been analyzed by natural bond orbital (NBO) analysis. Mulliken population analyses have been calculated. Finally, the molecular electrostatic potential (MEP) and HOMO-LUMO energy levels have been performed. The calculated HOMO and LUMO energies show also the charge transfer within the molecule. The energy gap obtained is about 4 eV which explain the stability of the studied compound. The obtained molecular electrostatic potential from the two methods confirms the nature of the electron charge transfer at the molecular shell and locate the electropositive part and the electronegative part in molecular scale of the title compound.

Keywords: DFT, ab initio, HOMO-LUMO, organic compounds

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3018 Turbulence Modeling and Wave-Current Interactions

Authors: A. C. Bennis, F. Dumas, F. Ardhuin, B. Blanke


The mechanics of rip currents are complex, involving interactions between waves, currents, water levels and the bathymetry, that present particular challenges for numerical models. Here, the effects of a grid-spacing dependent horizontal mixing on the wave-current interactions are studied. Near the shore, wave rays diverge from channels towards bar crests because of refraction by topography and currents, in a way that depends on the rip current intensity which is itself modulated by the horizontal mixing. At low resolution with the grid-spacing dependent horizontal mixing, the wave motion is the same for both coupling modes because the wave deviation by the currents is weak. In high-resolution case, however, classical results are found with the stabilizing effect of the flow by feedback of waves on currents. Lastly, wave-current interactions and the horizontal mixing strongly affect the intensity of the three-dimensional rip velocity.

Keywords: numerical modeling, wave-current interactions, turbulence modeling, rip currents

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3017 Molecular and Electronic Structure of Chromium (III) Cyclopentadienyl Complexes

Authors: Salem El-Tohami Ashoor


Here we show that the reduction of [Cr(ArN(CH2)3NAr)2Cl2] (1) where (Ar = 2,6-Pri2C6H3) and in presence of NaCp (2) (Cp= C5H5 = cyclopentadien), with a center coordination η5 interaction between Cp as co-ligand and chromium metal center, this was optimization by using density functional theory (DFT) and then was comparing with experimental data, also other possibility of Cp interacted with ion metal were tested like η1 ,η2 ,η3 and η4 under optimization system. These were carried out under investigation of density functional theory (DFT) calculation, and comparing together. Other methods, explicitly including electron correlation, are necessary for more accurate calculations; MB3LYP ( Becke)( Lee–Yang–Parr ) level of theory often being used to obtain more exact results. These complexes were estimated of electronic energy for molecular system, because it accounts for all electron correlation interactions. The optimised of [Cr(ArN(CH2)3NAr)2(η5-Cp)] (Ar = 2,6-Pri2C6H3 and Cp= C5H5) was found to be thermally more stable than others of chromium cyclopentadienyl. By using Dewar-Chatt-Duncanson model, as a basis of the molecular orbital (MO) analysis and showed the highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital LUMO.

Keywords: Chromium(III) cyclopentadienyl complexes, DFT, MO, HOMO, LUMO

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3016 Humans as Enrichment: Human-Animal Interactions and the Perceived Benefit to the Cheetah (Acinonyx jubatus), Human and Zoological Establishment

Authors: S. J. Higgs, E. Van Eck, K. Heynis, S. H. Broadberry


Engagement with non-human animals is a rapidly-growing field of study within the animal science and social science sectors, with human-interactions occurring in many forms; interactions, encounters and animal-assisted therapy. To our knowledge, there has been a wide array of research published on domestic and livestock human-animal interactions, however, there appear to be fewer publications relating to zoo animals and the effect these interactions have on the animal, human and establishment. The aim of this study was to identify if there were any perceivable benefits from the human-animal interaction for the cheetah, the human and the establishment. Behaviour data were collected before, during and after the interaction on the behaviour of the cheetah and the human participants to highlight any trends with nine interactions conducted. All 35 participants were asked to fill in a questionnaire prior to the interaction and immediately after to ascertain if their perceptions changed following an interaction with the cheetah. An online questionnaire was also distributed for three months to gain an understanding of the perceptions of human-animal interactions from members of the public, gaining 229 responses. Both questionnaires contained qualitative and quantitative questions to allow for specific definitive answers to be analysed, but also expansion on the participants perceived perception of human-animal interactions. In conclusion, it was found that participants’ perceptions of human-animal interactions saw a positive change, with 64% of participants altering their opinion and viewing the interaction as beneficial for the cheetah (reduction in stress assumed behaviours) following participation in a 15-minute interaction. However, it was noted that many participants felt the interaction lacked educational values and therefore this is an area in which zoological establishments can work to further improve upon. The results highlighted many positive benefits for the human, animal and establishment, however, the study does indicate further areas for research in order to promote positive perceptions of human-animal interactions and to further increase the welfare of the animal during these interactions, with recommendations to create and regulate legislation.

Keywords: Acinonyx jubatus, encounters, human-animal interactions, perceptions, zoological establishments

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3015 Geometric, Energetic and Topological Analysis of (Ethanol)₉-Water Heterodecamers

Authors: Jennifer Cuellar, Angie L. Parada, Kevin N. S. Chacon, Sol M. Mejia


The purification of bio-ethanol through distillation methods is an unresolved issue at the biofuel industry because of the ethanol-water azeotrope formation, which increases the steps of the purification process and subsequently increases the production costs. Therefore, understanding the mixture nature at the molecular level could provide new insights for improving the current methods and/or designing new and more efficient purification methods. For that reason, the present study focuses on the evaluation and analysis of (ethanol)₉-water heterodecamers, as the systems with the minimum molecular proportion that represents the azeotropic concentration (96 %m/m in ethanol). The computational modelling was carried out with B3LYP-D3/6-311++G(d,p) in Gaussian 09. Initial explorations of the potential energy surface were done through two methods: annealing simulated runs and molecular dynamics trajectories besides intuitive structures obtained from smaller (ethanol)n-water heteroclusters, n = 7, 8 and 9. The energetic order of the seven stable heterodecamers determines the most stable heterodecamer (Hdec-1) as a structure forming a bicyclic geometry with the O-H---O hydrogen bonds (HBs) where the water is a double proton donor molecule. Hdec-1 combines 1 water molecule and the same quantity of every ethanol conformer; this is, 3 trans, 3 gauche 1 and 3 gauche 2; its abundance is 89%, its decamerization energy is -80.4 kcal/mol, i.e. 13 kcal/mol most stable than the less stable heterodecamer. Besides, a way to understand why methanol does not form an azeotropic mixture with water, analogous systems ((ethanol)10, (methanol)10, and (methanol)9-water)) were optimized. Topologic analysis of the electron density reveals that Hec-1 forms 33 weak interactions in total: 11 O-H---O, 8 C-H---O, 2 C-H---C hydrogen bonds and 12 H---H interactions. The strength and abundance of the most unconventional interactions (H---H, C-H---O and C-H---O) seem to explain the preference of the ethanol for forming heteroclusters instead of clusters. Besides, O-H---O HBs present a significant covalent character according to topologic parameters as the Laplacian of electron density and the relationship between potential and kinetic energy densities evaluated at the bond critical points; obtaining negatives values and values between 1 and 2, for those two topological parameters, respectively.

Keywords: ADMP, DFT, ethanol-water azeotrope, Grimme dispersion correction, simulated annealing, weak interactions

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3014 Men and Feminism: Social Constructions of Masculinities in Relation to the Feminist Movement

Authors: Leonardo Dias Cruz


The advent of web 2.0 has enabled users to engage in translocal and transtemporal interactions in which meanings can be constantly (re)constructed. The fluidity of such interactions in the time-space spectrum makes it evident that D/discourses are always in movement and that here-and-now discursive practices are always linked to macro Discourses in social structures. Considering these assumptions, this study aims at exploring the social construction of masculinities in light of feminist D/discourses in online interactions. The data used are a series of comments from readers of articles posted in a website for (projected) male audiences. In order to approach the movable and fluid nature of such interactions, I examine the data through the lens of processes of entextualization, social positioning and indexical cues. The analysis explores the interactions as social arenas in which struggles for the control over entextualization processes are clearly noticeable. Moreover, two main stances are perceived: one that legitimates male’s participation in Feminism and one that rejects such participation.

Keywords: entextualization, feminism, masculinities, positionings

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3013 Improved Predictive Models for the IRMA Network Using Nonlinear Optimisation

Authors: Vishwesh Kulkarni, Nikhil Bellarykar


Cellular complexity stems from the interactions among thousands of different molecular species. Thanks to the emerging fields of systems and synthetic biology, scientists are beginning to unravel these regulatory, signaling, and metabolic interactions and to understand their coordinated action. Reverse engineering of biological networks has has several benefits but a poor quality of data combined with the difficulty in reproducing it limits the applicability of these methods. A few years back, many of the commonly used predictive algorithms were tested on a network constructed in the yeast Saccharomyces cerevisiae (S. cerevisiae) to resolve this issue. The network was a synthetic network of five genes regulating each other for the so-called in vivo reverse-engineering and modeling assessment (IRMA). The network was constructed in S. cereviase since it is a simple and well characterized organism. The synthetic network included a variety of regulatory interactions, thus capturing the behaviour of larger eukaryotic gene networks on a smaller scale. We derive a new set of algorithms by solving a nonlinear optimization problem and show how these algorithms outperform other algorithms on these datasets.

Keywords: synthetic gene network, network identification, optimization, nonlinear modeling

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3012 Location and Group Specific Differences in Human-Macaque Interactions in Singapore: Implications for Conflict Management

Authors: Srikantan L. Jayasri, James Gan


The changes in Singapore’s land use, natural preference of long-tailed macaques (Macaca fascicularis) to live in forest edges and their adaptability has led to interface between humans and macaques. Studies have shown that two-third of human-macaque interactions in Singapore were related to human food. We aimed to assess differences among macaques groups in their dependence on human food and interaction with humans as indicators of the level of interface. Field observations using instantaneous scan sampling and all occurrence ad-lib sampling were carried out for 23 macaque groups over 28 days recording 71.5 hours of observations. Data on macaque behaviour, demography, frequency, and nature of human-macaque interactions were collected. None of the groups were found to completely rely on human food source. Of the 23 groups, 40% of them were directly or indirectly provisioned by humans. One-third of the groups observed engaged in some form of interactions with the humans. Three groups that were directly fed by humans contributed to 83% of the total human-macaque interactions observed during the study. Our study indicated that interactions between humans and macaques exist in specific groups and in those fed by humans regularly. Although feeding monkeys is illegal in Singapore, such incidents seem to persist in specific locations. We emphasize the importance of group and location-specific assessment of the existing human-wildlife interactions. Conflict management strategies developed should be location specific to address the cause of interactions.

Keywords: primates, Southeast Asia, wildlife management, Singapore

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3011 Developing a Cybernetic Model of Interdepartmental Logistic Interactions in SME

Authors: Jonas Mayer, Kai-Frederic Seitz, Thorben Kuprat


In today’s competitive environment production’s logistic objectives such as ‘delivery reliability’ and ‘delivery time’ and distribution’s logistic objectives such as ‘service level’ and ‘delivery delay’ are attributed great importance. Especially for small and mid-sized enterprises (SME) attaining these objectives pose a key challenge. Within this context, one of the difficulties is that interactions between departments within the enterprise and their specific objectives are insufficiently taken into account and aligned. Interdepartmental independencies along with contradicting targets set within the different departments result in enterprises having sub-optimal logistic performance capability. This paper presents a research project which will systematically describe the interactions between departments and convert them into a quantifiable form.

Keywords: department-specific actuating and control variables, interdepartmental interactions, cybernetic model, logistic objectives

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3010 Synthesis and Application of Oligosaccharides Representing Plant Cell Wall Polysaccharides

Authors: Mads H. Clausen


Plant cell walls are structurally complex and contain a larger number of diverse carbohydrate polymers. These plant fibers are a highly valuable bio-resource and the focus of food, energy and health research. We are interested in studying the interplay of plant cell wall carbohydrates with proteins such as enzymes, cell surface lectins and antibodies. However, detailed molecular level investigations of such interactions are hampered by the heterogeneity and diversity of the polymers of interest. To circumvent this, we target well-defined oligosaccharides with representative structures that can be used for characterizing protein-carbohydrate binding. The presentation will highlight chemical syntheses of plant cell wall oligosaccharides from our group and provide examples from studies of their interactions with proteins.

Keywords: oligosaccharides, carbohydrate chemistry, plant cell walls, carbohydrate-acting enzymes

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