Search results for: molecular cloning

Authors: Mona Alharbi

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Melioidosis has emerged as a lethal disease. Unfortunately, the molecular mechanisms of virulence and pathogenicity of Burkholderia pseudomallei remain unknown. However, proteomics research has selected putative targets in B. pseudomallei that might play roles in the B. pseudomallei virulence. BPSL 2418 putative protein has been predicted as a free methionine sulfoxide reductase and interestingly there is a link between the level of the methionine sulfoxide in pathogen tissues and its virulence. Therefore in this work, we describe the cloning expression, purification, and crystallization of BPSL 2418 and the solution of its 3D structure using X-ray crystallography. Also, we aimed to identify the substrate binding and reduced forms of the enzyme to understand the role of BPSL 2418. The gene encoding BPSL2418 from B. pseudomallei was amplified by PCR and reclone in pETBlue-1 vector and transformed into E. coli Tuner DE3 pLacI. BPSL2418 was overexpressed using E. coli Tuner DE3 pLacI and induced by 300μM IPTG for 4h at 37°C. Then BPS2418 purified to better than 95% purity. The pure BPSL2418 was crystallized with PEG 4000 and PEG 6000 as precipitants in several conditions. Diffraction data were collected to 1.2Å resolution. The crystals belonged to space group P2 21 21 with unit-cell parameters a = 42.24Å, b = 53.48Å, c = 60.54Å, α=γ=β= 90Å. The BPSL2418 binding MES was solved by molecular replacement with the known structure 3ksf using PHASER program. The structure is composed of six antiparallel β-strands and four α-helices and two loops. BPSL2418 shows high homology with the GAF domain fRMsrs enzymes which suggest that BPSL2418 might act as methionine sulfoxide reductase. The amino acids alignment between the fRmsrs including BPSL 2418 shows that the three cysteines that thought to catalyze the reduction are fully conserved. BPSL 2418 contains the three conserved cysteines (Cys⁷⁵, Cys⁸⁵ and Cys¹⁰⁹). The active site contains the six antiparallel β-strands and two loops where the disulfide bond formed between Cys⁷⁵ and Cys¹⁰⁹. X-ray structure of free methionine sulfoxide binding and native forms of BPSL2418 were solved to increase the understanding of the BPSL2418 catalytic mechanism.

Keywords: X-Ray Crystallography, BPSL2418, Burkholderia pseudomallei, Melioidosis

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Authors: Rajandeep Kaur, Rajeev Gupta

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Background: Chronic myeloid leukemia (CML) is the most common leukaemia in India. The annual incidence of chronic myeloid leukemia in India was originally reported to be 0.8 to 2.2 per 1,00,000 population. CML is a clonal disorder that is usually easily diagnosed because the leukemic cells of more than 95% of patients have a distinctive cytogenetic abnormality, the Philadelphia chromosome (Ph1). The approval of tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity, has significantly reduced the mortality rate associated with chronic myeloid leukemia (CML) and revolutionized treatment. Material and Methods: 80 diagnosed cases of CML were taken. Investigations were done. Bone marrow and molecular studies were also done and with EUTOS, patients were stratified into low and high-risk groups and then treatment with Imatinib was given to all patients and the molecular response was evaluated at 6 months and 12 months follow up with BCR-ABL by RT-PCR quantitative assay. Results: In the study population, out of 80 patients in the study population, 40 were females and 40 were males, with M: F is 1:1. Out of total 80 patients’ maximum patients (54) were in 31-60 years age group. Our study showed a most common symptom of presentation is abdominal discomfort followed by fever. Out of the total 80 patients, 25 (31.3%) patients had high EUTOS scores and 55 (68.8%) patients had low EUTOS scores. On 6 months follow up 36.3% of patients had Complete Molecular Response, 16.3% of patients had Major Molecular Response and 47.5% of patients had No Molecular Response but on 12 months follow up 71.3% of patients had Complete Molecular Response, 16.25% of patients had Major Molecular Response and 12.5% patients had No Molecular Response. Conclusion: In this study, we found a significant correlation between EUTOS score and Molecular response at 6 months and 12 months follow up after Imatinib therapy.

Keywords: chronic myeloid leukemia, European treatment and outcome study score, hematological response, molecular response, tyrosine kinase inhibitor

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Authors: Mahsa Fathollahzadeh

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The quick advancement of nanotechnology necessitates the creation of innovative theoretical approaches to elucidate complex experimental findings and forecast novel capabilities of nanodevices. Therefore, over the past ten years, a difficult task in quantum chemistry has been comprehending electron and spin transport in molecular devices. This thorough evaluation presents a comprehensive overview of current research and its status in the field of molecular electronics, emphasizing the theoretical applications to various device types and including a brief introduction to theoretical methods and their practical implementation plan. The subject matter includes a variety of molecular mechanisms like molecular cables, diodes, transistors, electrical and visual switches, nano detectors, magnetic valve gadgets, inverse electrical resistance gadgets, and electron tunneling exploration. The text discusses both the constraints of the method presented and the potential strategies to address them, with a total of 183 references.

Keywords: chemistry, nanotechnology, quantum, molecule, spin

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Authors: Sanja O. Podunavac-Kuzmanović, Lidija R. Jevrić, Strahinja Z. Kovačević

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Benzimidazoles are a group of compounds with significant antibacterial, antifungal and anticancer activity. The studied compounds consist of the main benzimidazole structure with different combinations of substituens. This study is based on the two-dimensional and three-dimensional molecular modeling and calculation of molecular descriptors (physicochemical and lipophilicity descriptors) of structurally diverse benzimidazoles. Molecular modeling was carried out by using ChemBio3D Ultra version 14.0 software. The obtained 3D models 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. The obtained set of molecular descriptors was used in principal component analysis (PCA) of possible similarities and dissimilarities among the studied derivatives. After the molecular modeling, the quantitative structure-property relationship (QSPR) analysis was applied in order to get the mathematical models which can be used in prediction of pKb values of structurally similar benzimidazoles. The obtained models are based on statistically valid multiple linear regression (MLR) equations. The calculated cross-validation parameters indicate the high prediction ability of the established QSPR models. This study is financially supported by COST action CM1306 and the project No. 114-451-347/2015-02, financially supported by the Provincial Secretariat for Science and Technological Development of Vojvodina.

Keywords: benzimidazoles, chemometrics, molecular modeling, molecular descriptors, QSPR

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Authors: Jannes Quer, Amir Niknejad, Marcus Weber

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Computational Drug Design is often based on Molecular Dynamics simulations of molecular systems. Molecular Dynamics can be used to simulate, e.g., the binding and unbinding event of a small drug-like molecule with regard to the active site of an enzyme or a receptor. However, the time-scale of the overall binding event is many orders of magnitude longer than the time-scale of simulation. Thus, there is a need to speed-up molecular simulations. In order to speed up simulations, the molecular dynamics trajectories have to be ”steared” out of local minimizers of the potential energy surface – the so-called metastabilities – of the molecular system. Increasing the kinetic energy (temperature) is one possibility to accelerate simulated processes. However, with temperature the entropy of the molecular system increases, too. But this kind ”stearing” is not directed enough to stear the molecule out of the minimum toward the saddle point. In this article, we give a new mathematical idea, how a potential energy surface can be changed in such a way, that entropy is kept under control while the trajectories are still steared out of the metastabilities. In order to compute the unsteared transition behaviour based on a steared simulation, we propose to use extrapolation methods. In the end we mathematically show, that our method accelerates the simulations along the direction, in which the curvature of the potential energy surface changes the most, i.e., from local minimizers towards saddle points.

Keywords: extrapolation, Eyring-Kramers, metastability, multilevel sampling

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Authors: A. Azari, S. S. K. Seyyedi

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One of the unaddressed and open challenges in the nano-networking is the characteristics of noise. The previous analysis, however, has concentrated on end-to-end communication model with no separate modelings for propagation channel and noise. By considering a separate signal propagation and noise model, the design and implementation of an optimum receiver will be much easier. In this paper, we justify consideration of a separate additive Gaussian noise model of a nano-communication system based on the molecular communication channel for which are applicable for MSK and MOSK modulation schemes. The presented noise analysis is based on the Brownian motion process, and advection molecular statistics, where the received random signal has a probability density function whose mean is equal to the mean number of the received molecules. Finally, the justification of received signal magnitude being uncorrelated with additive non-stationary white noise is provided.

Keywords: molecular, noise, diffusion, channel

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Authors: Paweł Stączek, Tomasz Plech, Aleksandra Strzelczyk, Katarzyna Dzitko, Monika Wujec, Edyta Kuśmierz, Piotr Paneth, Agata Paneth

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In this contribution, we will describe the inhibitory potency of nine thiosemicarbazide derivatives against bacterial type IIA topoisomerases, their antibacterial profile, and molecular modeling evaluation. We have found that one of the tested compounds, 4-benzoyl-1-(2-methyl-furan-3-ylcarbonyl) thiosemicarbazide, remarkably inhibits the activity of S. aureus DNA gyrase with the IC50 below 5 μM. Besides, this compound displays antibacterial activity on Staphylococcus spp. and E. faecalis at non-cytotoxic concentrations in mammalian cells, with minimal inhibitory concentrations (MICs) values at 25 μg/mL. Based on the enzymatic and molecular modeling studies we propose two factors, i.e. geometry of molecule and hydrophobic/hydrophilic balance as important molecular properties for developing thiosemicarbazide derivatives as potent Staphylococcus aureus DNA gyrase inhibitors.

Keywords: bioactivity, drug design, topoisomerase, molecular modeling

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Authors: Hai Hoang, Thanh Xuan Nguyen Thi, Guillaume Galliero

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Coarse-Grained (CG) molecular simulations have shown to be an efficient way to estimate thermophysical (static and dynamic) properties of fluids. Several strategies have been developed and reported in the literature for defining CG molecular models. Among them, those based on a top-down strategy (i.e. CG molecular models related to macroscopic observables), despite being heuristic, have increasingly gained attention. This is probably due to its simplicity in implementation and its ability to provide reasonable results for not only simple but also complex systems. Regarding simple Force-Fields associated with these CG molecular models, it has been found that the four parameters Mie chain model is one of the best compromises to describe thermophysical static properties (e.g. phase diagram, saturation pressure). However, parameterization procedures of these Mie-chain GC molecular models given in literature are generally insufficient to simultaneously provide static and dynamic (e.g. viscosity) properties. To deal with such situations, we have extended the corresponding states by using a quantity associated with the liquid viscosity. Results obtained from molecular simulations have shown that our approach is able to yield good estimates for both static and dynamic thermophysical properties for various real non-associating fluids. In addition, we will show that on simple (e.g. phase diagram, saturation pressure) and complex (e.g. thermodynamic response functions, thermodynamic energy potentials) static properties, results of our scheme generally provides improved results compared to existing approaches.

Keywords: coarse-grained model, mie potential, molecular simulations, thermophysical properties, phase equilibria

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Authors: Manel Boulakoud, Abdelkader Chouaih, Fodil Hamzaoui

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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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Authors: Efendi Zaenudin, Chien-Hung Huang, Ka-Lok Ng

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Essential genes play an important role in the survival of an organism. It has been shown that cancer-associated essential genes are genes necessary for cancer cell proliferation, where these genes are potential therapeutic targets. Also, it was demonstrated that mutations of the cancer-associated essential genes give rise to the resistance of immunotherapy for patients with tumors. In the present study, we focus on studying the biological effects of the essential genes from a network perspective. We hypothesize that one can analyze a biological molecular network by decomposing it into both three-node and four-node digraphs (subgraphs). These network subgraphs encode the regulatory interaction information among the network’s genetic elements. In this study, the frequency of occurrence of the subgraph-associated essential genes in a molecular network was quantified by using the statistical parameter, odds ratio. Biological effects of subgraph-associated essential genes are discussed. In summary, the subgraph approach provides a systematic method for analyzing molecular networks and it can capture useful biological information for biomedical research.

Keywords: biological molecular networks, essential genes, graph theory, network subgraphs

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Authors: Y. Megrous, A. Chouaih, F. Hamzaoui

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The crystal structure of 4-Methyl-7-(salicylideneamino)coumarin C17H13NO3has been determined using X-ray diffraction to establish the configuration and stereochemistry of the molecule. This crystal is characterized by its nolinear activity. The molecular electron charge density distribution of the title compound is described accurately using the multipolar model of Hansen and Coppens. The net atomic charge and the molecular dipole moment in-crystal have been determined in order to understand the nature of inter-and intramolecular charge transfer. The study present the thermal motion and the structural analysis obtained from the least-square refinement on F2,this study has also allowed us to determine the electrostatic potential and therefore locate the electropositive part and the electronegative part in molecular scale of the title compound.

Keywords: electron charge density, net atomic charge, molecular dipole moment, X-ray diffraction

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Authors: I-Ling Chang, Jer-An Chen

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The elastic properties and fracture of two-dimensional graphene were calculated purely from the atomic bonding (stretching and bending) based on molecular mechanics method. Considering the representative unit cell of graphene under various loading conditions, the deformations of carbon bonds and the variations of the interlayer distance could be realized numerically under the geometry constraints and minimum energy assumption. In elastic region, it was found that graphene was in-plane isotropic. Meanwhile, the in-plane deformation of the representative unit cell is not uniform along armchair direction due to the discrete and non-uniform distributions of the atoms. The fracture of graphene could be predicted using fracture criteria based on the critical bond length, over which the bond would break. It was noticed that the fracture behavior were directional dependent, which was consistent with molecular dynamics simulation results.

Keywords: energy minimization, fracture, graphene, molecular mechanics

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Authors: Jing Zhao, Yongqing Bai, Qiaofang Shi, Huaihao Zhang

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Advances in software technology enable computational chemistry to be commonly applied in various research fields, especially in pedagogy. Thus, in order to expand and improve experimental instructions of computational chemistry for undergraduates, we designed an introductory experiment—research on acrylamide molecular structure and physicochemical properties. Initially, students construct molecular models of acrylamide and polyacrylamide in Gaussian and Materials Studio software respectively. Then, the infrared spectral data, atomic charge and molecular orbitals of acrylamide as well as solvation effect of polyacrylamide are calculated to predict their physicochemical performance. At last, rheological experiments are used to validate these predictions. Through the combination of molecular simulation (performed on Gaussian, Materials Studio) with experimental verification (rheology experiment), learners have deeply comprehended the chemical nature of acrylamide and polyacrylamide, achieving good learning outcomes.

Keywords: upper-division undergraduate, computer-based learning, laboratory instruction, molecular modeling

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Authors: Sakina Fatima, Joseph-Patrick W. E. Clarke, Patricia A. Thibault, Subha Kalyaanamoorthy, Michael Levin, Aravindhan Ganesan

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Heteronuclear ribonucleoprotein (hnRNPA1 or A1) is associated with the pathology of different diseases, including neurological disorders and cancers. In particular, the aggregation and dysfunction of A1 have been identified as a critical driver for neurodegeneration (NDG) in Multiple Sclerosis (MS). Structurally, A1 includes a low-complexity domain (LCD) and two RNA-recognition motifs (RRMs), and their interdomain coordination may play a crucial role in A1 aggregation. Previous studies propose that RNA-inhibitors or nucleoside analogs that bind to RRMs can potentially prevent A1 self-association. Therefore, molecular-level understanding of the structures, dynamics, and nucleotide interactions with A1 RRMs can be useful for developing therapeutics for NDG in MS. In this work, a combination of computational modelling and biochemical experiments were employed to analyze a set of RNA-A1 RRM complexes. Initially, the atomistic models of RNA-RRM complexes were constructed by modifying known crystal structures (e.g., PDBs: 4YOE and 5MPG), and through molecular docking calculations. The complexes were optimized using molecular dynamics simulations (200-400 ns), and their binding free energies were computed. The binding affinities of the selected complexes were validated using a thermal shift assay. Further, the most important molecular interactions that contributed to the overall stability of the RNA-A1 RRM complexes were deduced. The results highlight that adenine and guanine are the most suitable nucleotides for high-affinity binding with A1. These insights will be useful in the rational design of nucleotide-analogs for targeting A1 RRMs.

Keywords: hnRNPA1, molecular docking, molecular dynamics, RNA-binding proteins

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Authors: Salem El-Tohami Ashoor

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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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Authors: Milica Karadzic, Lidija Jevric, Sanja Podunavac-Kuzmanovic, Strahinja Kovacevic, Sinisa Markov, Aleksandar Okljesa, Andrea Nikolic, Marija Sakac, Katarina Penov Gasi

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This study considered the microbiological activity determination and molecular docking study for selected steroid derivatives of biomedical importance. Minimal inhibitory concentration (MIC) was determined for steroid derivatives against Staphylococcus aureus using macrodilution method. Some of the investigated steroid derivatives express bacteriostatic effect against Staphylococcus aureus. Molecular docking approaches are the most widely used techniques for predicting the binding mode of a ligand. Molecular docking study was done for steroid derivatives for androgen receptor negative prostate cancer cell line (PC-3) toward Human Cytochrome P450 CYP17A1. The molecules that had the smallest experimental IC50 values confirmed their ability to dock into active place using suitable molecular docking procedure. The binding disposition of those molecules was thoroughly investigated. Microbiological analysis and molecular docking study were conducted with aim to additionally characterize selected steroid derivatives for future investigation regarding their biological activity and to estimate the binding-affinities of investigated derivatives. This article is based upon work from COST Action (TD1305), supported by COST (European Cooperation and Science and Technology).

Keywords: binding affinity, minimal inhibitory concentration, molecular docking, pc-3 cell line, staphylococcus aureus, steroids

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Authors: Lethukuthula Ngobese, Abin Gupthar, Patrick Govender

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The ability of yeast cell wall-derived mannoproteins (glycoproteins) to positively contribute to oenological properties has been a key factor that stimulates research initiatives into these industrially important glycoproteins. In addition, and from a fundamental research perspective, yeast cell wall glycoproteins are involved in a wide range of biological interactions. To date, and to the best of our knowledge, our understanding of the fine molecular structure of these mannoproteins is fairly limited. Generally, the amino acid sequences of their protein moieties have been established from structural and functional analysis of the genomic sequence of these yeasts whilst far less information is available on the glycosyl moieties of these mannoproteins. A novel strategy was devised in this study that entails the genetic engineering of yeast strains that over-express and release cell wall-associated glycoproteins into the liquid growth medium. To this end, the Flo1p mannoprotein was overexpressed in Saccharomyces cerevisiae laboratory strains bearing a specific deletion in KNR4 and GPI7 genes involved in cell wall biosynthesis that have been previously shown to extracellularly hyper-secrete cell wall-associated glycoproteins. A polymerase chain reaction (PCR) -based cloning strategy was employed to generate transgenic yeast strains in which the native cell wall FLO1 glycoprotein-encoding gene is brought under transcriptional control of the constitutive PGK1 promoter. The modified Helm’s flocculation assay was employed to assess flocculation intensities of a Flo1p over-expressing wild type and deletion mutant as an indirect measure of their abilities to release the desired mannoprotein. The flocculation intensities of the transformed strains were assessed and all the strains showed similar intensities (>98% flocculation). To assess if mannoproteins were released into the growth medium, the supernatant of each strain was subjected to the BCA protein assay and the transformed Δknr4 strain showed a considerable increase in protein levels. This study has the potential to produce mannoproteins in sufficient quantities that may be employed in future investigations to understand their molecular structures and mechanisms of interaction to the benefit of both fundamental and industrial applications.

Keywords: glycoproteins, genetic engineering, flocculation, over-expression

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Authors: Jayanthi Sivaraman

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Claudins are the important components of the tight junctions that play a key role in paracellular permeability. Among various members of Claudin family, Claudin 4 (CLDN4) is found to be overexpressed in ovarian, pancreatic carcinomas and other epithelial malignancies. Therefore, in this study, an attempt has been made to identify potent inhibitors for CLDN4 from the ZINC database using virtual screening, molecular docking and molecular dynamics simulations. A well refined molecular model of CLDN4 was built using Prime of Schrodinger v10.2(Template- PDB ID: 4P79). Approximately, 6 million compounds from ZINC database are subjected to high-throughput virtual screening (HTVS) against the active site of CLDN4. Molecular docking using GLIDE predicted ARG31, ASN142, ASP146 and ARG158 as critically important residues. Furthermore, three compounds from ZINC database (ZINC96331839, ZINC36533519 and ZINC75819394) showed highly promising ADME properties and binding affinity with stable conformation. The therapeutic efficiency of these lead compounds is evaluated and confirmed by in-vitro and in-vivo studies which leads to the development of novel anti-cancer drugs.

Keywords: ADME property, inhibitors, molecular docking, virtual screening

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Authors: Guohua Cao, Xu Dong

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X-ray Fluorescence Molecular Imaging (XFMI) holds great promise as a low-cost molecular imaging modality for biomedical applications with high chemical sensitivity. However, for in vivo biomedical applications, a key technical bottleneck is the relatively low chemical sensitivity of XFMI, especially at a reasonably low radiation dose. In laboratory x-ray source based XFMI, one of the main factors that limits the chemical sensitivity of XFMI is the scattered x-rays. We will present our latest findings on improving the chemical sensitivity of XFMI using excitation beam spectrum optimization. XFMI imaging experiments on two mouse-sized phantoms were conducted at three different excitation beam spectra. Our results show that the minimum detectable concentration (MDC) of iodine can be readily increased by five times via excitation spectrum optimization. Findings from this investigation could find use for in vivo pre-clinical small-animal XFMI in the future.

Keywords: molecular imaging, X-ray fluorescence, chemical sensitivity, X-ray scattering

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Authors: Begüm Terzi, Özlem Ateş Sönmezoğlu, Ahmet Yildirim

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Drought is the most important factor that limiting the production and productivity of wheat in the world. The yield of wheat, which is one of the most important crop in the world, reduced depend on drought. Researches to minimize effects of drought are one of the most important about breeding of drought resistant varieties. In recent years, benefiting from the drought resistance wild species and rapid advances in molecular biology studies, researches about drought have been accelerated and number of studies were made on molecular plant breeding which included the molecular mechanisms related to drought resistance. The aim of the present study was characterization of some bread wheat lines for drought tolerance which commonly cultivated in different location of Turkey. In this study, registered 9 bread wheat varieties which on the physiological tests about drought tolerance and 10 bread wheat line has been developed by Transitional Zone Agricultural Research Institute were used. SSR, STS, RAPD and SNP markers that associated with drought tolerance were used. The polymorphisms of the markers were determined by screening of two control varieties. For these purpose 40 molecular markers were used and 12 markers of them were polymorphic among the drought tolerance and the drought sensitive varieties. Control varieties were screened using polymorphic markers. All the DNAs on the genotypes will be searched for the presence of QTLs mapped to different chromosomes. Result of the research, the studied genotypes will be grouped according to drought tolerance and will be detected drought tolerance varieties by molecular markers. In addition, the results will be compared also with physiological tests. The drought tolerant wheat genotypes may be used in breeding studies related to drought stress.

Keywords: bread wheat, drought, molecular marker, Triticum aestivum

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Authors: Asli Faiza, Khamouli Saida

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With the development of computer tools over the past 20 years. Molecular modeling and, more precisely, molecular docking has very quickly entered field of pharmaceutical research. EGFR enzyme involved in cancer disease.Our work consists of studying the inhibition of EGFR (1M17) with deferent inhibitors derived from quinazoline and quinoline by molecular docking. The values of ligands L148 and L177 are the best ligands for inhibit the activity of 1M17 since it forms a stable complex with this enzyme by better binding to the active site. The results obtained show that the ligands L148 and L177 give weak interactions with the active site residues EGFR (1M17), which stabilize the complexes formed of this ligands, which gives a better binding at the level of the active site, and an RMSD of L148 [1,9563 Å] and of L177 [ 1,2483 Å]. [1, 9563, 1.2483] Å

Keywords: docking, EGFR, quinazoline, quinoliène, MOE

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Authors: Mohamad Mohsen Yavarizadeh

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Polystyrene (PS) and related homopolymers are brittle materials that typically fail in tensile tests at very low strains. These polymers can be toughened by the addition of rubbery particles which initiate a large number of crazes that produce substantial plastic strain at relatively low stresses. Considerable energy is dissipated in the formation of these crazes, producing a relatively tough material that shows an impact toughness of more than 5 times of pure PS. While cross linking of rubbery phase is necessary in aforementioned mechanism of toughening, another mechanism of toughening was also introduced in which low molecular weight liquid rubbers can also toughen PS when dispersed in the form of small pools in the glassy matrix without any cross linking. However, this new mechanism which is based on local plasticization, fails to act properly at high strain rate deformations, i.e. impact tests. In this work, the idea of combination of these two mechanisms was tried. To do so, Polybutadiene rubbers (PB) with bimodal distribution of molecular weight were prepared in which, comparable fractions of very high and very low molecular weight rubbers were mixed. Incorporation of these materials in PS matrix in a reactive process resulted in more significant increases in toughness of PS. In other words, although low molecular weight PB is ineffective in high strain rate impact test by itself, it showed a significant synergistic effect when combined with high molecular weight PB. Surprisingly, incorporation of just 10% of low molecular weight PB doubled the impact toughness of regular high impact PS (HIPS). It was observed that most of rubbery particles could initiate crazes. The effectiveness of low molecular weight PB in impact test was attributed to low strain rate deformation of each individual craze as a result of producing a large number of crazes in this material. In other words, high molecular weight PB chains make it possible to have an appropriate dispersion of rubbery phase in order to create a large number of crazes in the PS matrix and consequently decrease the velocity of each craze. Low molecular weight PB, in turn, would have enough time to locally plasticize craze fibrils and enhance the energy dissipation.

Keywords: molecular weight distribution, polystyrene, toughness, homopolymer

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Authors: Moulay Driss Mellaoui, Khadija Zaki, Khalid Abbiche, Abdallah Imjjad, Rachid Boutiddar, Abdelouahid Sbai, Aaziz Jmiai, Souad El Issami, Al Mokhtar Lamsabhi, Hanane Zejli

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This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, leveraging a multifaceted approach that combines Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Through DFT analysis, using the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, we optimized molecular geometries, analyzed vibrational frequencies, and mapped Molecular Electrostatic Potentials (MEP), identifying key sites for electrophilic attacks and hydrogen bonding. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b showing slightly higher stability. Chemical potential assessments indicated differences in binding affinities, suggesting stronger potential interactions for compounds 1b and 2b. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, highlighting compound 3b superior oral effectiveness. Molecular docking and molecular dynamics simulations were conducted on isoxazolidine and 4-isoxazoline derivatives targeting the EGFR receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, among the isoxazolidine derivatives, compound 3b exhibited the most favorable binding energy, with a g score of -8.50 kcal/mol. Molecular dynamics simulations over 100 nanoseconds demonstrated the stability and potential of compound 3b as a superior candidate for anticancer applications, further supported by structural analyses including RMSD, RMSF, Rg, and SASA values. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.

Keywords: isoxazolines, DFT, molecular docking, molecular dynamic, ADMET, drugs.

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Authors: Ashkan Forootan, Reza Rashedi

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Polyethylene has wide usage areas such as blow molding, pipe, film, cable insulation. However, regardless to its growing applications, it has some constraints such as the limited 70C operating temperature. Polyethylene thermo setting procedure whose molecules are knotted and 3D-molecular-network formed , is developed to conquer the above problem and to raise the applicable temperature of the polymer. This paper reports the cross-linking for two different molecular weight grades of LLDPE by adding 0.5, 1, and 2% of DCP (Dicumyl Peroxide). DCP was chosen for its prevalence among various cross-linking agents. Structural parameters such as molecular weight, melt flow index, comonomer, number of branches,etc. were obtained through the use of relative tests as Gel Permeation Chromatography and Fourier Transform Infra Red spectrometer. After calculating the percentage of gel content, properties of the pure and cross-linked samples were compared by thermal and mechanical analysis with DMTA and FTIR and the effects of cross-linking like viscous and elastic modulus were discussed by using various structural paprameters such as MFI, molecular weight, short chain branches, etc. Studies showed that cross-linked polymer, unlike the pure one, had a solid state with thermal mechanical properties in the range of 110 to 120C and this helped overcome the problem of using polyethylene in temperatures near the melting point.

Keywords: LLDPE, cross-link, structural parameters, DCP, DMTA, GPC

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Authors: Strahinja Z. Kovačević, Lidija R. Jevrić, Sanja O. Podunavac Kuzmanović

Abstract:

The relationship between antibacterial activity of eighteen different substituted benzimidazole derivatives and their molecular characteristics was studied using chemometric QSAR (Quantitative Structure–Activity Relationships) approach. QSAR analysis has been carried out on inhibitory activity towards Staphylococcus aureus, by using molecular descriptors, as well as minimal inhibitory activity (MIC). Molecular descriptors were calculated from the optimized structures. Principal component analysis (PCA) followed by hierarchical cluster analysis (HCA) and multiple linear regression (MLR) was performed in order to select molecular descriptors that best describe the antibacterial behavior of the compounds investigated, and to determine the similarities between molecules. The HCA grouped the molecules in separated clusters which have the similar inhibitory activity. PCA showed very similar classification of molecules as the HCA, and displayed which descriptors contribute to that classification. MLR equations, that represent MIC as a function of the in silico molecular descriptors were established. The statistical significance of the estimated models was confirmed by standard statistical measures and cross-validation parameters (SD = 0.0816, F = 46.27, R = 0.9791, R2CV = 0.8266, R2adj = 0.9379, PRESS = 0.1116). These parameters indicate the possibility of application of the established chemometric models in prediction of the antibacterial behaviour of studied derivatives and structurally very similar compounds.

Keywords: antibacterial, benzimidazole, molecular descriptors, QSAR

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Authors: W. Soufi, F. Boukli Hacene, S. Ghalem

Abstract:

Alzheimer's disease (AD) is a neurodegenerative disease that leads to a progressive and permanent deterioration of nerve cells. This disease is progressively accompanied by an intellectual deterioration leading to psychological manifestations and behavioral disorders that lead to a loss of autonomy. It is the most frequent of degenerative dementia. Alzheimer's disease (AD), which affects a growing number of people, has become a major public health problem in a few years. In the context of the study of the mechanisms governing the evolution of AD disease, we have found that natural flavonoids are good acetylcholinesterase inhibitors that reduce the rate of ßA secretion in neurons. This work is to study the inhibition of acetylcholinesterase (AChE) which is an enzyme involved in Alzheimer's disease, by methods of molecular modeling. These results will probably help in the development of an effective therapeutic tool in the fight against the development of Alzheimer's disease. Our goal of the research is to study the inhibition of acetylcholinesterase (AChE) by molecular modeling methods.

Keywords: Alzheimer's disease, acetylcholinesterase, flavonoids, molecular modeling

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Authors: Aliyu Adamu, Fahrul Huyop, Roswanira Abdul Wahab, Mohd Shahir Shamsir

Abstract:

Halogenated organic compounds occur in huge amount in biosphere. This is attributable to the diverse use of halogen-based compounds in the synthesis of various industrially important products. Halogenated compound is toxic and may persist in the environment, thereby causing serious health and environmental pollution problems. L-2-haloacid dehalogenases (EC 3.8.1.2) catalyse the specific cleavage of carbon-halogen bond in L-isomers of halogenated compounds, which consequently reverse the effects of environmental halogen-associated pollution. To enhance the efficiency and utility of these enzymes, this study investigates the catalytic amino acid residues and the molecular functional mechanism of DehL, by classical molecular dynamic simulations, MM-PBSA and ab initio fragments molecular orbital (FMO) calculations. The results of the study will serve as the basis for the molecular engineering of the enzyme.

Keywords: DehL, Functional mechanism, Catalytic residues, L-2-haloacid dehalogenase

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Authors: F. Boukli Hacene, W. Soufi, S. Ghalem

Abstract:

Glaucoma disease is a progressive degenerative optic neuropathy, with irreversible visual field deficits and high eye pressure being one of the risk factors. Sulfonamides are carbonic anhydrase-II inhibitors that aim to decrease the secretion of aqueous humor by direct inhibition of this enzyme at the level of the ciliary processes. These drugs present undesirable effects that are difficult to accept by the patient. In our study, we are interested in the inhibition of carbonic anhydrase-II by different natural ligands (curcumin analogues) using molecular modeling methods using molecular operating environment (MOE) software to predict their interaction with this enzyme.

Keywords: carbonic anhydrase-II, curcumin analogues, drug research, molecular modeling

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Authors: Ainoa Guinart, Maria Korpidou, Daniel Doellerer, Cornelia Palivan, Ben L. Feringa

Abstract:

Stimuli responsive systems arise from the need to meet unsolved needs of current molecular drugs. Our study presents the design of a delivery system with high spatiotemporal control and tuneable release profiles. We study the incorporation of a hydrophobic synthetic molecular motor into PDMS-b-PMOXA block copolymer vesicles to create a self-assembled system. We prove their successful incorporation and selective activation by low powered visible light (λ 430 nm, 6.9 mW). We trigger the release of a fluorescent dye with high release efficiencies over sequential cycles (up to 75%) with the ability to turn on and off the release behaviour on demand by light irradiation. Low concentrations of photo-responsive units are proven to trigger release down to 1 mol% of molecular motor. Finally, we test our system in relevant physiological conditions using a lung cancer cell line and the encapsulation of an approved drug. Similar levels of cell viability are observed compared to the free-given drugshowing the potential of our platform to deliver functional drugs on demand with the same efficiency and lower toxicity.

Keywords: molecular motor, polymer, drug delivery, light-responsive, cancer, selfassembly

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Authors: Kaining Zhang, Lang Chen, Danyang Liu, Jianying Lu, Kun Yang, Junying Wu

Abstract:

In order to solve the problem of a large amount of simulation and limited simulation scale in the first-principle molecular dynamics simulation of energetic material detonation reaction, we established an artificial intelligence model for analyzing and predicting the detonation reaction mechanism of CL-20 based on the first-principle molecular dynamics simulation of the multiscale shock technique (MSST). We employed principal component analysis to identify the dominant charge features governing molecular reactions. We adopted the K-means clustering algorithm to cluster the reaction paths and screen out the key reactions. We introduced the neural network algorithm to construct the mapping relationship between the charge characteristics of the molecular structure and the key reaction characteristics so as to establish a calculation method for predicting detonation reactions based on the charge characteristics of CL-20 and realize the rapid analysis of the reaction mechanism of energetic materials.

Keywords: energetic material detonation reaction, first-principle molecular dynamics simulation of multiscale shock technique, neural network, CL-20

Procedia PDF Downloads 77