Search results for: molecular interactions

Authors: Desta Gebretekle Shiferaw, Balakrishna Kalluraya

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Oxadiazoles and their derivatives with thioether functionalities represent a new and exciting class of physiologically active heterocyclic compounds. Several molecules with these moieties play a vital role in pharmaceuticals because of their diverse biological activities. This paper describes a new class of 1,3,4- oxadiazole-2-thioethers with acetophenone, coumarin, and N-phenyl acetamide residues (S-alkylation), with the hope that the addition of various biologically active molecules will have a synergistic effect on anticancer activity. The structure of the synthesized title compounds was determined by the combined methods of IR, proton-NMR, carbon-13-NMR, and mass spectrometry. Further, all the newly prepared molecules were assessed against their antioxidant activity. Furthermore, four compounds were assessed for their molecular docking interactions and cytotoxicity activity. The synthesized derivatives have shown moderate antioxidant activity compared to the standard BHA. The IC50 of the tilted molecules (11b, 11c, 13b, and 14b) observed for in vitro anti-cancer activities were 11.20, 15.73, 59.61, and 27.66 g/ml at 72-hour treatment time against the A549 cell lines, respectively. The tested compounds' biological evaluation showed that 11b is the most effective molecule in the series.

Keywords: antioxidant activity, cytotoxicity activity, molecular docking, 1, 3, 4-Oxadiazole-2 thioether derivatives

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Authors: Srikantan L. Jayasri, James Gan

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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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Authors: Hamza Javar Magnier, Robin Curtis

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There have been rapid advances in the upstream processing of protein therapeutics, which has shifted the bottleneck to downstream purification and formulation. Finding liquid formulations with shelf lives of up to two years is increasingly difficult for some of the newer therapeutics, which have been engineered for activity, but their formulations are often viscous, can phase separate, and have a high propensity for irreversible aggregation1. We explore means to develop improved predictive ability from a better understanding of how protein-protein interactions on formulation conditions (pH, ionic strength, buffer type, presence of excipients) and how these impact upon the initial steps in protein self-association and aggregation. In this work, we study the initial steps in the aggregation pathways using a minimal protein model based on square-well potentials and discontinuous molecular dynamics. The effect of model parameters, including range of interaction, stiffness, chain length, and chain sequence, implies that protein models fold according to various pathways. By reducing the range of interactions, the folding- and collapse- transition come together, and follow a single-step folding pathway from the denatured to the native state2. After parameterizing the model interaction-parameters, we developed an understanding of low-temperature conformational properties and fluctuations, and the correlation to the folding transition of proteins in isolation. The model fluctuations increase with temperature. We observe a low-temperature point, below which large fluctuations are frozen out. This implies that fluctuations at low-temperature can be correlated to the folding transition at the melting temperature. Because proteins “breath” at low temperatures, defining a native-state as a single structure with conserved contacts and a fixed three-dimensional structure is misleading. Rather, we introduce a new definition of a native-state ensemble based on our understanding of the core conservation, which takes into account the native fluctuations at low temperatures. This approach permits the study of a large range of length and time scales needed to link the molecular interactions to the macroscopically observed behaviour. In addition, these models studied are parameterized by fitting to experimentally observed protein-protein interactions characterized in terms of osmotic second virial coefficients.

Keywords: protein folding, native-ensemble, conformational fluctuation, aggregation

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

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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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Authors: Virendra Nath, Vipin Kumar

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Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.

Keywords: computational, diabetes, PPAR, simulation

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Authors: Catherine Vasnetsov, Victor Vasnetsov

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Context: Thermo-responsive polymers are materials that undergo significant changes in their physical properties in response to temperature changes. These polymers have gained significant attention in research due to their potential applications in various industries and medicine. However, the molecular mechanisms underlying their behavior are not well understood, particularly in relation to cosolvency, which is crucial for practical applications. Research Aim: This study aimed to theoretically investigate the phenomenon of cosolvency in long-chain polymers using the Flory-Huggins statistical-mechanical framework. The main objective was to understand the interactions between the polymer, solvent, and cosolvent under different conditions. Methodology: The research employed a combination of Monte Carlo computer simulations and advanced machine-learning methods. The Flory-Huggins mean field theory was used as the basis for the simulations. Spinodal graphs and ternary plots were utilized to develop an initial computer model for predicting polymer behavior. Molecular dynamic simulations were conducted to mimic real-life polymer systems. Machine learning techniques were incorporated to enhance the accuracy and reliability of the simulations. Findings: The simulations revealed that the addition of very low or very high volumes of cosolvent molecules resulted in smaller radii of gyration for the polymer, indicating poor miscibility. However, intermediate volume fractions of cosolvent led to higher radii of gyration, suggesting improved miscibility. These findings provide a possible microscopic explanation for the cosolvency phenomenon in polymer systems. Theoretical Importance: This research contributes to a better understanding of the behavior of thermo-responsive polymers and the role of cosolvency. The findings provide insights into the molecular mechanisms underlying cosolvency and offer specific predictions for future experimental investigations. The study also presents a more rigorous analysis of the Flory-Huggins free energy theory in the context of polymer systems. Data Collection and Analysis Procedures: The data for this study was collected through Monte Carlo computer simulations and molecular dynamic simulations. The interactions between the polymer, solvent, and cosolvent were analyzed using the Flory-Huggins mean field theory. Machine learning techniques were employed to enhance the accuracy of the simulations. The collected data was then analyzed to determine the impact of cosolvent volume fractions on the radii of gyration of the polymer. Question Addressed: The research addressed the question of how cosolvency affects the behavior of long-chain polymers. Specifically, the study aimed to investigate the interactions between the polymer, solvent, and cosolvent under different volume fractions and understand the resulting changes in the radii of gyration. Conclusion: In conclusion, this study utilized theoretical modeling and computer simulations to investigate the phenomenon of cosolvency in long-chain polymers. The findings suggest that moderate cosolvent volume fractions can lead to improved miscibility, as indicated by higher radii of gyration. These insights contribute to a better understanding of the molecular mechanisms underlying cosolvency in polymer systems and provide predictions for future experimental studies. The research also enhances the theoretical analysis of the Flory-Huggins free energy theory.

Keywords: molecular modelling, flory-huggins, cosolvency, stimuli-responsive polymers

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Authors: Rauan Sakenov, Peter Bukovics, Peter Gaszler, Veronika Tokacs-Kollar, Beata Bugyi

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FH2 (formin homology-2) domains of several proteins, collectively known as formins, including DAAM, DAAM1 and mDia1, promote G-actin nucleation and elongation. FH2 domains of these formins exist as oligomers. Chain dimerization by ring structure formation serves as a structural basis for actin polymerization function of FH2 domain. Proper single chain configuration and specific interactions between its various regions are necessary for individual chains to form a dimer functional in G-actin nucleation and elongation. FH1 and WH2 domain-containing formins were shown to behave as intrinsically disordered proteins. Thus, the aim of this research was to study structural dynamics of FH2 domain of DAAM. To investigate structural features of FH2 domain of DAAM, molecular dynamics simulation of chain A of FH2 domain of DAAM solvated in water box in 50 mM NaCl was conducted at temperatures from 293.15 to 353.15K, with VMD 1.9.2, NAMD 2.14 and Amber Tools 21 using 2z6e and 1v9d PDB structures of DAAM was obtained on I-TASSER webserver. Calcium and ATP bound G-actin 3hbt PDB structure was used as a reference protein with well-described structural dynamics of denaturation. Topology and parameter information of CHARMM 2012 additive all-atom force fields for proteins, carbohydrate derivatives, water and ions were used in NAMD 2.14 and ff19SB force field for proteins in Amber Tools 21. The systems were energy minimized for the first 1000 steps, equilibrated and produced in NPT ensemble for 1ns using stochastic Langevin dynamics and the particle mesh Ewald method. Our root-mean square deviation (RMSD) analysis of molecular dynamics of chain A of FH2 domains of DAAM revealed similar insignificant changes of total molecular average RMSD values of FH2 domain of these formins at temperatures from 293.15 to 353.15K. In contrast, total molecular average RMSD values of G-actin showed considerable increase at 328K, which corresponds to the denaturation of G-actin molecule at this temperature and its transition from native, ordered, to denatured, disordered, state which is well-described in the literature. RMSD values of lasso and tail regions of chain A of FH2 domain of DAAM exhibited higher than total molecular average RMSD at temperatures from 293.15 to 353.15K. These regions are functional in intra- and interchain interactions and contain highly conserved tryptophan residues of lasso region, highly conserved GNYMN sequence of post region and amino acids of the shell of hydrophobic pocket of the salt bridge between Arg171 and Asp321, which are important for structural stability and ordered state of FH2 domain of DAAM and its functions in FH2 domain dimerization. In conclusion, higher than total molecular average RMSD values of lasso and post regions of chain A of FH2 domain of DAAM may explain disordered state of FH2 domain of DAAM at temperatures from 293.15 to 353.15K. Finally, absence of marked transition, in terms of significant changes in average molecular RMSD values between native and denatured states of FH2 domain of DAAM at temperatures from 293.15 to 353.15K, can make it possible to attribute these formins to the group of intrinsically disordered proteins rather than to the group of intrinsically ordered proteins such as G-actin.

Keywords: FH2 domain, DAAM, formins, molecular modelling, computational biophysics

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Authors: R. Mohan, V. Jadhav, A. Ahmed, J. Rivas, A. Kelkar

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Cementitious materials are an excellent example of a composite material with complex hierarchical features and random features that range from nanometer (nm) to millimeter (mm) scale. Multi-scale modeling of complex material systems requires starting from fundamental building blocks to capture the scale relevant features through associated computational models. In this paper, molecular dynamics (MD) modeling is employed to predict the effect of plasticizer additive on the mechanical properties of key hydrated cement constituent calcium-silicate-hydrate (CSH) at the molecular, nanometer scale level. Due to complexity, still unknown molecular configuration of CSH, a representative configuration widely accepted in the field of mineral Jennite is employed. The effectiveness of the Molecular Dynamics modeling to understand the predictive influence of material chemistry changes based on molecular/nanoscale models is demonstrated.

Keywords: cement composite, mechanical properties, molecular dynamics, plasticizer additives

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Authors: M. Kowalik, J. Masternak, K. Kazimierczuk, O. V. Khavryuchenko, B. Kupcewicz, B. Barszcz

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Recently, the growing interest of chemists in metal-organic coordination polymers (MOCPs) is primarily derived from their intriguing structures and potential applications in catalysis, gas storage, molecular sensing, ion exchanges, nonlinear optics, luminescence, etc. Currently, we are devoting considerable effort to finding the proper method of synthesizing new coordination polymers containing S- or N-heteroaromatic carboxylates as linkers and characterizing the obtained Pb(II) compounds according to their structural diversity, luminescence, and thermal properties. The choice of Pb(II) as the central ion of MOCPs was motivated by several reasons mentioned in the literature: i) a large ionic radius allowing for a wide range of coordination numbers, ii) the stereoactivity of the 6s2 lone electron pair leading to a hemidirected or holodirected geometry, iii) a flexible coordination environment, and iv) the possibility to form secondary bonds and unusual non-covalent interactions, such as classic hydrogen bonds and π···π stacking interactions, as well as nonconventional hydrogen bonds and rarely reported tetrel bonds, Pb(lone pair)···π interactions, C–H···Pb agostic-type interactions or hydrogen bonds, and chelate ring stacking interactions. Moreover, the construction of coordination polymers requires the selection of proper ligands acting as linkers, because we are looking for materials exhibiting different network topologies and fluorescence properties, which point to potential applications. The reaction of Pb(NO₃)₂ with 1H-pyrrole-2-carboxylic acid (2prCOOH) leads to the formation of a new four-nuclear Pb(II) polymer, [Pb4(2prCOO)₈(H₂O)]ₙ, which has been characterized by CHN, FT-IR, TG, PL and single-crystal X-ray diffraction methods. In view of the primary Pb–O bonds, Pb1 and Pb2 show hemidirected pentagonal pyramidal geometries, while Pb2 and Pb4 display hemidirected octahedral geometries. The topology of the strongest Pb–O bonds was determined as the (4·8²) fes topology. Taking the secondary Pb–O bonds into account, the coordination number of Pb centres increased, Pb1 exhibited a hemidirected monocapped pentagonal pyramidal geometry, Pb2 and Pb4 exhibited a holodirected tricapped trigonal prismatic geometry, and Pb3 exhibited a holodirected bicapped trigonal prismatic geometry. Moreover, the Pb(II) lone pair stereoactivity was confirmed by DFT calculations. The 2D structure was expanded into 3D by the existence of non-covalent O/C–H···π and Pb···π interactions, which was confirmed by the Hirshfeld surface analysis. The above mentioned interactions improve the rigidity of the structure and facilitate the charge and energy transfer between metal centres, making the polymer a promising luminescent compound.

Keywords: coordination polymers, fluorescence properties, lead(II), lone electron pair stereoactivity, non-covalent interactions

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Authors: Monisha Isaac

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Use of molecular markers for selecting plants with desired traits has been started long back. Due to their heritable characteristics, they are useful for identification and characterization of specific genotypes. The study involves various types of molecular markers used to select multiple desired characters in plants, their properties, and advantages to improve crop productivity in adverse climatological conditions for the purpose of providing food security to fast-growing global population. The study shows that genetic similarities obtained from molecular markers provide more accurate information and the genetic diversity can be better estimated from the genetic relationship obtained from the dendrogram. The information obtained from markers assisted characterization is more suitable for the crops of economic importance like sugarcane.

Keywords: molecular markers, crop productivity, genetic diversity, genotype

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Authors: Susan Burkett-McKee, Bruce Knight, Michelle Vanderburg

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The wellbeing and educational success of high ability students are interrelated concepts with each potentially hindering or enhancing the other. A student’s well-being and educational success are also influenced by intrapersonal and interpersonal factors. This presentation begins with an exploration of the literature pertinent to the wellbeing and educational success of this cohort before an ecological perspective is taken to discuss research into the impact of interactions within the school context. While the literature consistently states that interactions exchanged between high ability students and school community members impact the students’ wellbeing or educational success, no consensus has been reached about whether the impact is positive or negative. Findings from the review shared in this presentation inform an interpretative phenomenological study involving senior secondary students enrolled in inclusive Australian schools to highlight, from the students’ perspective, the ways school-based interactions impact their wellbeing or educational success.

Keywords: educational success, interactions, literature review, wellbeing

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Authors: Ferid Hammami

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The molecular geometries of the possible conformations of pyruvic acid-water complexes (PA-(H₂O)ₙ = 1- 4) have been fully optimized at DFT/B3LYP/6-311G ++ (d, p) levels of calculation. Among several optimized molecular clusters, the most stable molecular arrangements obtained when one, two, three, and four water molecules are hydrogen-bonded to a central pyruvic acid molecule are presented in this paper. Apposite topological and geometrical parameters are considered as primary indicators of H-bond strength. Atoms in molecules (AIM) analysis shows that pyruvic acid can form a ring structure with water, and the molecular structures are stabilized by both strong O-H...O and C-H...O hydrogen bonds. In large clusters, classical O-H...O hydrogen bonds still exist between water molecules, and a cage-like structure is built around some parts of the central molecule of pyruvic acid. The electrostatic potential energy map (MEP) and the HOMO-LUMO molecular orbital (highest occupied molecular orbital-lowest unoccupied molecular orbital) analysis has been performed for all considered complexes.

Keywords: pyruvic acid, PA-water complex, hydrogen bonding, DFT, AIM, MEP, HOMO-LUMO

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Authors: Seyedmajid Mehrnia, Maximilan Kuhr, Peter F. Pelz

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Molecular Dynamics (MD) simulation is a proven method to inspect behaviours of lubricant oils in nano-scale gaps. However, most MD simulations on tribology have been performed with atomically smooth walls to determine wall slip and friction properties. This study will investigate the effect of porosity, specifically nano-porous walls, on wall slip properties of hydrocarbon oils confined between two walls in a Couette flow. Different pore geometries will be modelled to investigate the effect on wall slip and bulk shear. In this paper, the Polyalphaolefin (PAO) molecules are confined to a stationary and a moving wall. A hybrid force field consisting of different potential energy functions was employed in this MD simulation. Newton’s law defines how those forces will influence the atoms' movements. The interactions among surface atoms were simulated with an Embedded Atom Method (EAM) potential function which can represent the characteristics of metallic arrangements very strongly. We implemented NERD forcefield for intramolecular potential energy function. Also, Lennard-Jones potential was employed for nonbonded intermolecular interaction.

Keywords: slip length, molecular dynamics, critical shear rate, Couette flow

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Authors: Tivani Phosa Mashamba-Thompson, Mahmoud E. S. Soliman

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To date, the cause of neurodegeneration is not well understood and diseases that stem from neurodegeneration currently have no known cures. Cathepsin B (CB) enzyme is known to be involved in the production of peptide neurotransmitters and toxic peptides in neurodegenerative diseases (NDs). CA-074Me is a membrane-permeable irreversible selective cathepsin B (CB) inhibitor as confirmed by in vivo studies. Due to the lack of the crystal structure, the binding mode of CA-074Me with the human CB at molecular level has not been previously reported. The main aim of this study is to gain an insight into the binding mode of CB CA-074Me to human CB using various computational tools. Herein, molecular dynamics simulations, binding free energy calculations and per-residue energy decomposition analysis were employed to accomplish the aim of the study. Another objective was to identify novel CB inhibitors based on the structure of CA-074Me using fragment based drug design using scaffold hoping drug design approach. Results showed that two of the designed ligands (hit 1 and hit 2) were found to have better binding affinities than the prototype inhibitor, CA-074Me, by ~2-3 kcal/mol. Per-residue energy decomposition showed that amino acid residues Cys29, Gly196, His197 and Val174 contributed the most towards the binding. The Van der Waals binding forces were found to be the major component of the binding interactions. The findings of this study should assist medicinal chemist towards the design of potential irreversible CB inhibitors.

Keywords: cathepsin B, scaffold hopping, docking, molecular dynamics, binding-free energy, neurodegerative diseases

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Authors: Fernanda Miranda da Cruz

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This paper aims to systematize, descriptively and analytically, the relations between language, body and material world explored in a specific empirical context: everyday co-presence interactions between children diagnosed with Autistic Spectrum Disease ASD and various interlocutors. We will work based on 20 hours of an audiovisual corpus in Brazilian Portuguese language. This analysis focuses on 1) the analysis of daily interactions that have the presence/participation of subjects with a diagnosis of ASD based on an embodied interaction perspective; 2) the study of the status and role of gestures, body and material world in the construction and constitution of human interaction and its relation with linguistic-cognitive processes and Autistic Spectrum Disorders; 3) to highlight questions related to the field of videoanalysis, such as: procedures for recording interactions in complex environments (involving many participants, use of objects and body movement); the construction of audiovisual corpora for linguistic-interaction research; the invitation to a visual analytical mentality of human social interactions involving not only the verbal aspects that constitute it, but also the physical space, the body and the material world.

Keywords: autism spectrum disease, multimodality, social interaction, non-verbal interactions

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Authors: Sara Ataei, Molouk Hadjibabaie, Shirinsadat Badri, Amirhossein Moslehi, Iman Karimzadeh, Ardeshir Ghavamzadeh

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Purpose: To assess the pattern and probable risk factors for moderate and major drug–drug interactions in a referral hematology-oncology ward in Iran. Methods: All patients admitted to hematology–oncology ward of Dr. Shariati Hospital during a 6-month period and received at least two anti-cancer or non-anti-cancer medications simultaneously were included. All being scheduled anti-cancer and non-anti-cancer medications both prescribed and administered during ward stay were considered for drug–drug interaction screening by Lexi-Interact On- Desktop software. Results: One hundred and eighty-five drug–drug interactions with moderate or major severity were detected from 83 patients. Most of drug–drug interactions (69.73 %) were classified as pharmacokinetics. Fluconazole (25.95 %) was the most commonly offending medication in drug–drug interactions. Interaction of sulfamethoxazole-trimethoprim with fluconazole was the most common drug–drug interaction (27.27 %). Vincristine with imatinib was the only identified interaction between two anti-cancer agents. The number of administered medications during ward stay was considered as an independent risk factor for developing a drug–drug interaction. Conclusions: Potential moderate or major drug–drug interactions occur frequently in patients with hematological malignancies or related diseases. Performing larger standard studies are required to assess the real clinical and economical effects of drug–drug interactions on patients with hematological and non-hematological malignancies.

Keywords: drug–drug interactions, hematology–oncology ward, hematological malignancies

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Authors: Sanja Podunavac-Kuzmanović, Strahinja Kovačević, Lidija Jevrić, Evgenija Djurendić, Jovana Ajduković

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In the present study, the molecular modeling of a series of 24 17-picolyl and 17-picolinylidene androstane derivatives whit significant anticancer activity was carried out. Modelling of studied compounds was performed by CS ChemBioDraw Ultra v12.0 program for drawing 2D molecular structures and CS ChemBio3D Ultra v12.0 for 3D molecular modelling. The obtained 3D structures were subjected to energy minimization using molecular mechanics force field method (MM2). The cutoff for structure optimization was set at a gradient of 0.1 kcal/Åmol. Full geometry optimization was done by the Austin Model 1 (AM1) until the root mean square (RMS) gradient reached a value smaller than 0.0001 kcal/Åmol using Molecular Orbital Package (MOPAC) program. The obtained physicochemical, lipophilicity and topological descriptors were used for analysis of molecular similarities and dissimilarities applying suitable chemometric methods (principal component analysis and cluster analysis). These results are the part of the project No. 114-451-347/2015-02, financially supported by the Provincial Secretariat for Science and Technological Development of Vojvodina and CMST COST Action CM1306.

Keywords: androstane derivatives, anticancer activity, chemometrics, molecular descriptors

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Authors: Debjit Dutta, P. Roy, O. Panella

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In recent years, non Hermitian interaction in non relativistic as well as relativistic quantum mechanics have been examined from various aspect. We can observe interesting fact that for such systems a class of potentials, namely the PT symmetric and η-pseudo Hermitian admit real eigenvalues despite being non Hermitian and analogues of those system have been experimentally verified. Point to be noted that relativistic non Hermitian (PT symmetric) interactions can be realized in optical structures and also there exists photonic realization of the (1 + 1) dimensional Dirac oscillator. We have thoroughly studied generalized Dirac oscillators with non Hermitian interactions in (1 + 1) dimensions. To be more specific, we have examined η pseudo Hermitian interactions within the framework of generalized Dirac oscillator in (1 + 1) dimensions. In particular, we have obtained a class of interactions which are η-pseudo Hermitian and the metric operator η could have been also found explicitly. It is possible to have exact solutions of the generalized Dirac oscillator for some choices of the interactions. Subsequently we have employed the mapping between the generalized Dirac oscillator and the Jaynes Cummings (JC) model by spin flip to obtain a class of exactly solvable non Hermitian JC as well as anti Jaynes Cummings (AJC) type models.

Keywords: Dirac oscillator, non-Hermitian quantum system, Hermitian, relativistic

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Authors: P. Haldar, P. Ghosh, S. Ghoshdastidar, K. Kargupta

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In polymer electrolyte membrane fuel cells (PEMFC), the membrane electrode assembly (MEA) is consisting of two platinum coated carbon electrodes, sandwiched with one proton conducting phosphoric acid doped polymeric membrane. Due to low mechanical stability, flooding and fuel cell crossover, application of phosphoric acid in polymeric membrane is very critical. Phosphorous and silica based 3D inorganic gel gains the attention in the field of supercapacitors, fuel cells and metal hydrate batteries due to its thermally stable highly proton conductive behavior. Also as a large amount of water molecule and phosphoric acid can easily get trapped in Si-O-Si network cavities, it causes a prevention in the leaching out. In this study, we have performed molecular dynamics (MD) simulation and first principle calculations to understand the structural, electronics and electrochemical and morphological behavior of this inorganic gel at various P to Si ratios. We have used dipole-dipole interactions, H bonding, and van der Waals forces to study the main interactions between the molecules. A 'structure property-performance' mapping is initiated to determine optimum P to Si ratio for best proton conductivity. We have performed the MD simulations at various temperature to understand the temperature dependency on proton conductivity. The observed results will propose a model which fits well with experimental data and other literature values. We have also studied the mechanism behind proton conductivity. And finally we have proposed a structure for the gel paste with optimum P to Si ratio.

Keywords: first principle calculation, molecular dynamics simulation, phosphorous and silica based 3D inorganic gel, polymer electrolyte membrane fuel cells, proton conductivity

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Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

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Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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Authors: Daniel C. S. Lim, Eric Y. M. Yeo, W. Y. Tan

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This paper presents an overview of how calcium interacts with the various essential nutrients within an environment of cellular and hormonal interactions for the purpose of increasing bioavailability to the human body. One example of such interactions can be illustrated with calcium homeostasis. This paper gives an in-depth discussion on the possible interactive permutations with various nutrients and factors leading to the promotion of calcium bioavailability to the body. The review hopes to provide further insights into how calcium supplement formulations can be improved to better influence its bioavailability in the human body.

Keywords: bioavailability, environment of cellular and hormonal interactions, nutritional combinations, synergistic

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Authors: Andrey Angorsky

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In the article an issue about the possible number of fundamental physical interactions is studied. The theory of similarity on the dimensionless quantity as the damping ratio serves as the instrument of analysis. The structure with the features of Higgs field comes out from non-commutative expression for this ratio. The experimentally checked up supposition about the nature of dark energy is spoken out.

Keywords: damping ratio, dark energy, dimensionless quantity, fundamental physical interactions, Higgs field, non-commutative expression

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Authors: Archana Gupta, Rajesh Kumar

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The chemistry of chalcones has generated intensive scientific studies throughout the world. Especially, interest has been focused on the synthesis and biodynamic activities of chalcones. The blue light transmittance, excellent crystallizability and the two planar rings connected through a conjugated double bond show that chalcone derivatives are superior nonlinear organic compounds. 3-(2-Chloro-6-fluoro¬phen¬yl)-1-(2-thien¬yl) prop-2-en-1-one, 3-(2, 4- Dichlorophenyl) – 1 - (4-methylphenyl) – prop -2-en-1-one, (2E)-3-[4-(methylsulfanyl) phenyl]-1-(4-nitrophenyl) prop-2-en-1-one are some chalcone derivatives exhibiting non linear optical (NLO) properties. NLO materials have been extensively investigated in recent years as they are the key elements for photonic technologies of optical communication, optical interconnect oscillator, amplifier, frequency converter etc. Due to their high molecular hyperpolarizabilities, organic materials display a number of significant NLO properties. Experimental measurements and theoretical calculations on molecular hyperpolarizability β have become one of the key factors in the design of second order NLO materials. Theoretical determination of hyperpolarizability is quite useful both in understanding the relationship between the molecular structure and NLO properties. It also provides a guideline to experimentalists for the design and synthesis of organic NLO materials. Quantum-chemical calculations have made an important contribution to the understanding of the electronic polarization underlying the molecular NLO processes and the establishment of structure–property relationships. In the present investigation, the detailed vibrational analysis of some chalcone derivatives is taken up to understand the correlation of the charge transfer interaction and the NLO activity of the molecules based on density functional theory calculations. The vibrational modes contributing toward the NLO activity have been identified and analyzed. Rather large hyperpolarizability derived by theoretical calculations suggests the possible future use of these compounds for non-linear optical applications. The study suggests the importance of π - conjugated systems for non-linear optical properties and the possibility of charge transfer interactions. We hope that the results of the present study of chalcone derivatives are of assistance in development of new efficient materials for technological applications.

Keywords: hyperpolarizability, molecular structure, NLO material, quantum chemical calculations

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Authors: Sinethemba Yakobi, Lindiwe Zuma, Ofentse Pooe

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Gonococcal infections present a notable public health issue, and the major approach for treatment involves using β-lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in Neisseria gonorrhoeae. This study examines the influence of flavonoids, namely rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research clarifies the structural effects of particular mutations, such as inserting an aspartate residue at position 345 (Asp-345a) in the PBP2 protein. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely P551S and F504L, significantly impact the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasizing its exceptional binding affinity and potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in N. gonorrhoeae. Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant N. gonorrhoeae bacteria. The verified simulation outcomes establish a basis for creating potent inhibitors and medicinal therapies to combat infectious illnesses.

Keywords: phytochemicals, penicillin-binding protein 2, gonococcal infection, ligand-protein interaction, binding energy, neisseria gonorrhoeae FA19, neisseria gonorrhoeae FA6140, flavonoids

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

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Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential Cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L were in-silico screened using molecular docking, pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect towards the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interactions stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries towards the rational development of potent anti-Alzheimer agents.

Keywords: alzheimer’s disease, molecular docking, cannabis sativa l, cholinesterase inhibitors

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Authors: K. Veluraja

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Glycan of glycolipids and glycoproteins is playing a significant role in living systems particularly in molecular recognition processes. Molecular recognition processes are attributed to their occurrence on the surface of the cell, sequential arrangement and type of sugar molecules present in the oligosaccharide structure and glyosidic linkage diversity (glycoinformatics) and conformational diversity (glycoconformatics). Molecular Dynamics Simulation study is a theoretical-cum-computational tool successfully utilized to establish glycoconformatics of glycan. The study on various oligosaccharides of glycan clearly indicates that oligosaccharides do exist in multiple conformational states and these conformational states arise due to the flexibility associated with a glycosidic torsional angle (φ,ψ) . As an example: a single disaccharide structure NeuNacα(2-3) Gal exists in three different conformational states due to the differences in the preferential value of glycosidic torsional angles (φ,ψ). Hence establishing three dimensional structural and conformational models for glycan (cartesian coordinates of every individual atoms of an oligosaccharide structure in a preferred conformation) is quite crucial to understand various molecular recognition processes such as glycan-toxin interaction and glycan-virus interaction. The gycoconformatics models obtained for various glycan through Molecular Dynamics Simulation stored in our 3DSDSCAR (3DSDSCAR.ORG) a public domain database and its utility value in understanding the molecular recognition processes and in drug design venture will be discussed.

Keywords: glycan, glycoconformatics, molecular dynamics simulation, oligosaccharide

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Authors: Amir Bahrami

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In the fields of chemical graph theory, molecular topology, and mathematical chemistry, a topological index or a descriptor index also known as a connectivity index is a type of a molecular descriptor that is calculated based on the molecular graph of a chemical compound. Topological indices are numerical parameters of a graph which characterize its topology and are usually graph invariant. Topological indices are used for example in the development of quantitative structure-activity relationships (QSARs) in which the biological activity or other properties of molecules are correlated with their chemical structure. In this paper some descriptor index (descriptor index) of single-walled carbon nanotubes, is determined.

Keywords: chemical graph theory, molecular topology, molecular descriptor, single-walled carbon nanotubes

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Authors: Dafna Knani, Sarit S. Sivan

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Aggrecan, one of the main components of the intervertebral disc (IVD), belongs to the family of proteoglycans (PGs) that are composed of glycosaminoglycan (GAG) chains covalently attached to a core protein. Its primary function is to maintain tissue hydration and hence disc height under the high loads imposed by muscle activity and body weight. Significant PG loss is one of the first indications of disc degeneration. A possible solution to recover disc functions is by injecting a synthetic hydrogel into the joint cavity, hence mimicking the role of PGs. One of the hydrogels proposed is GAG-analogues, based on sulfate-containing polymers, which are responsible for hydration in disc tissue. In the present work, we used molecular dynamics (MD) to study the effect of the hydrogel crosslinking (type and degree) on the swelling behavior of the suggested GAG-analogue biomimetics by calculation of cohesive energy density (CED), solubility parameter, enthalpy of mixing (ΔEmix) and the interactions between the molecules at the pure form and as a mixture with water. The simulation results showed that hydrophobicity plays an important role in the swelling of the hydrogel, as indicated by the linear correlation observed between solubility parameter values of the copolymers and crosslinker weight ratio (w/w); this correlation was found useful in predicting the amount of PEGDA needed for the desirable hydration behavior of (CS)₄-peptide. Enthalpy of mixing calculations showed that all the GAG analogs, (CS)₄ and (CS)₄-peptide are water-soluble; radial distribution function analysis revealed that they form interactions with water molecules, which is important for the hydration process. To conclude, our simulation results, beyond supporting the experimental data, can be used as a useful predictive tool in the future development of biomaterials, such as disc replacement.

Keywords: molecular dynamics, proteoglycans, enthalpy of mixing, swelling

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Authors: Wenjun Zhang, Yunqing Du, Steven W. Cranford, Ming L. Wang

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The beginning of 21st century has witnessed new advancements in the design and use of new materials for biosensing applications, from nano to macro, protein to tissue. Traditional analytical methods lack a complete toolset to describe the complexities introduced by living systems, pathological relations, discrete hierarchical materials, cross-phase interactions, and structure-property dependencies. Materiomics – via systematic molecular dynamics (MD) simulation – can provide structure-process-property relations by using a materials science approach linking mechanisms across scales and enables oriented biosensor design. With this approach, DNA biosensors can be utilized to detect disease biomarkers present in individuals’ breath such as acetone for diabetes. Our wireless sensor array based on single-stranded DNA (ssDNA)-decorated single-walled carbon nanotubes (SWNT) has successfully detected trace amount of various chemicals in vapor differentiated by pattern recognition. Here, we present how MD simulation can revolutionize the way of design and screening of DNA aptamers for targeting biomarkers related to oral diseases and oral health monitoring. It demonstrates great potential to be utilized to build a library of DNDA sequences for reliable detection of several biomarkers of one specific disease, and as well provides a new methodology of creating, designing, and applying of biosensors.

Keywords: biosensor, DNA, biomarker, molecular dynamics simulation

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Authors: Elzbieta Babula, Juhyun Park

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Tversky and Kahneman’s cumulative prospect theory assumes symmetric probability cumulation with regard to the reference point within decision weights. Theoretically, this model should be invariant under the change of the direction of probability cumulation. In the present study, this phenomenon is being investigated by creating a reference model that allows verifying the parameter interactions in the cumulative prospect theory specifications. The simultaneous parametric fitting of utility and weighting functions is applied to binary choice data from the experiment. The results show that the flexibility of the probability weighting function is a crucial characteristic allowing to prevent parameter interactions while estimating cumulative prospect theory.

Keywords: binary choice experiment, cumulative prospect theory, decision weights, parameter interactions

Procedia PDF Downloads 183