Search results for: in silico molecular docking

Authors: M. Zemouli, K. Amara, M. Elkeurti, Y. Benallou

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We present a theoretical study of the structural, elastic and thermodynamic properties of the zinc-blende AlBi for a wide temperature range. The simulation calculation is performed in the framework of the molecular dynamics method using the three-body Tersoff potential which reproduces provide, with reasonable accuracy, the lattice constants and elastic constants. Our results for the lattice constant, the bulk modulus and cohesive energy are in good agreement with other theoretical available works. Other thermodynamic properties such as the specific heat and the lattice thermal expansion can also be predicted. In addition, this method allows us to check its ability to predict the phase transition of this compound. In particular, the transition pressure to the rock-salt phase is calculated and the results are compared with other available works.

Keywords: aluminium compounds, molecular dynamics simulations, interatomic potential, thermodynamic properties, structural phase transition

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Authors: D. S. Malatesh, K. J. Ananda, C. Ansar Kamran, K. Ganesh Udupa

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Dirofilaria repens is a mosquito-borne filarioid nematode of dogs and other carnivores and accidentally affects humans. D. repens is reported in many countries, including India. Subcutaneous dirofilariosis caused by D. repens is a zoonotic disease, widely distributed throughout Europe, Asia, and Africa, with higher prevalence reported in dogs from Sri Lanka (30-60%), Iran (61%) and Italy (21-25%). Dirofilariasis in dogs was diagnosed by detection of microfilariae in blood. Identification of different Dirofilaria species was done by using molecular methods like polymerase chain reaction (PCR). Even though many researchers reported molecular evidence of D. repens across India, to our best knowledge there is no data available on molecular diagnosis of D. repens in dogs and its zoonotic implication in Karnataka state a southern state in India. The aim of the present study was to identify the Dirofilaria species occurring in dogs from Karnataka, India. Out of 310 samples screened for the presence of microfilariae using traditional diagnostic methods, 99 (31.93%) were positive for the presence of microfilariae. Based on the morphometry, the microfilariae were identified as D. repens. For confirmation of species, the samples were subjected to PCR using pan filarial primers (DIDR-F1, DIDR-R1) for amplification of internal transcribed spacer region 2 (ITS2) of the ribosomal DNA. The PCR product of 484 base pairs on agarose gel was indicative of D. repens. Hence, a single PCR reaction using pan filarial primers can be used to differentiate filarial species found in dogs. The present study confirms that dirofilarial species occurring in dogs from Karnataka is D. repens and further sequencing studies are needed for genotypic characterization of D. repens.

Keywords: Dirofilaria repens, molecular characterization, polymerase chain reaction, Karnataka, India

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Authors: Boda Sreenivas, Lyathakula Ravindranath, Kanugula Srishailam, Byru Venkatram Reddy

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Extensive research into the optimized structure and molecular properties of 3-Flouro-2-methylbenzoicacid(FMB), 3-Chloro-2-methoxybenzoicacid (CMB), and 3-Bromo-2-methylbenzoicacid (BMB) was carried out using FT-IR, FT-Raman and UV-Visible spectra, as well as theoretically using the DFT approach with B3LYPfunctional in conjunction with 6-311++G(d,p) basis set. The optimized structure was determined by evaluating torsional scans about free rotation bonds. Structure parameters, harmonic vibrational frequencies, potential energy distribution(PED), and infrared and Raman intensities were computed. The computational results from the DFT approach, such asFT-IR, FT-Raman, and UV-Visible spectra, were compared with the experimental results and found good agreement. Observed and calculated frequencies agreed with an rms error of 8.42, 6.60, and 6.95 cm-1 for FMB, CMB, and BMB, respectively. Unambiguous vibrational assignments were made for all fundamentals using PED and eigenvectors. The electronic HOMO-LUMO, H-bonding, and strong conjugative interactions across different molecular entities are discussed using experimental and simulated Ultraviolet-Visible spectra. The title molecules' molecular properties such as dipole moment, mean polarizability, and first-order hyperpolarizability, were calculated to study their non-linear optical (NLO) behavior. The chemical reactivity descriptors and mapped electrostatic surface potential (MESP) were also evaluated. Natural bond orbital (NBO) analysis was used to examine the stability of molecules resulting from hyperconjugative interactions and charge delocalization.

Keywords: ftir/raman spectra, DFT, NLO, homo-lumo, NBO, halogenated benzoic acids

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Authors: M. Dehestani, F. Kamali, M. Klantari Pour, L. Zeidabadi-Nejad

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Chemical bonding between polyethylene glycol (PEG) with pharmaceutical proteins called pegylation is one of the most effective methods of improving the pharmacological properties. The covalent attachment of polyethylene glycol (PEG) to proteins will increase their pharmacologic properties. For the formation of a combination of pegylated protein should first be activated PEG and connected to the protein. Interferons(IFNs) are a family of cytokines which show antiviral effects in front of the biological and are responsible for setting safety system. In this study, the nature and properties of the interaction between active positions of IFNs and polyethylene glycol have been investigated using molecular dynamics simulation. The main aspect of this theoretical work focuses on the achievement of valuable data on the reaction pathways of PEG-IFNs and the transition state energy. Our results provide a new perspective on the interactions, chemical properties and reaction pathways between IFNs and PEG.

Keywords: interaction, interferons, molecular dynamics simulation, polyethylene glycol

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Authors: Mahdi Asghari

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The cavitation phenomenon is the formation and production of micro-bubbles and eventually the bursting of the micro-bubbles inside the liquid fluid, which results in localized high pressure and temperature, causing physical and chemical fluid changes. This pressure and temperature are predicted to be 2000 atmospheres and 5000 °C, respectively. As a result of small bubbles bursting from this process, temperature and pressure increase momentarily and locally, so that the intensity and magnitude of these temperatures and pressures provide the energy needed to break the molecular bonds of heavy compounds such as fuel oil. In this paper, we study the theory of cavitation and the methods of cavitation production by acoustic and hydrodynamic methods and the necessary mechanical equipment and reactors for industrial application of the hydrodynamic cavitation method to break down the molecular bonds of the fuel oil and convert it into useful and economical products.

Keywords: Cavitation, Hydrodynamic Cavitation, Cavitation Reactor, Fuel Oil

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Authors: A. Rezaei, M. Huisman, W. Van Paepegem

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Atomic interactions in molecular systems are mainly studied by particle mechanics. Nevertheless, researches have also put on considerable effort to simulate them using continuum methods. In early 2000, simple equivalent finite element models have been developed to study the mechanical properties of carbon nanotubes and graphene in composite materials. Afterward, many researchers have employed similar structural simulation approaches to obtain mechanical properties of nanostructured materials, to simplify interface behavior of fiber-reinforced composites, and to simulate defects in carbon nanotubes or graphene sheets, etc. These structural approaches, however, are limited to small deformations due to complicated local rotational coordinates. This article proposes a method for the finite element simulation of molecular mechanics. For ease in addressing the approach, here it is called Structural Finite Element Molecular Modeling (SFEMM). SFEMM method improves the available structural approaches for large deformations, without using any rotational degrees of freedom. Moreover, the method simulates molecular conformation, which is a big advantage over the previous approaches. Technically, this method uses nonlinear multipoint constraints to simulate kinematics of the atomic multibody interactions. Only truss elements are employed, and the bond potentials are implemented through constitutive material models. Because the equilibrium bond- length, bond angles, and bond-torsion potential energies are intrinsic material parameters, the model is independent of initial strains or stresses. In this paper, the SFEMM method has been implemented in ABAQUS finite element software. The constraints and material behaviors are modeled through two Fortran subroutines. The method is verified for the bond-stretch, bond-angle and bond-torsion of carbon atoms. Furthermore, the capability of the method in the conformation simulation of molecular structures is demonstrated via a case study of a graphene sheet. Briefly, SFEMM builds up a framework that offers more flexible features over the conventional molecular finite element models, serving the structural relaxation modeling and large deformations without incorporating local rotational degrees of freedom. Potentially, the method is a big step towards comprehensive molecular modeling with finite element technique, and thereby concurrently coupling an atomistic domain to a solid continuum domain within a single finite element platform.

Keywords: finite element, large deformation, molecular mechanics, structural method

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Authors: Bakhtishod Matmuratov, Sakhiba Madraximova, Rakhmat Esanov, Alimjan Matchanov

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Studies have been performed to obtain complexes of glycyrrhizic acid and kinetins in a 2:1 ratio. The complex of glycyrrhizic acid and kinetins in a 2:1 ratio was considered evidence of the formation of a molecular complex by determining the molecular masses using chromato-mass spectroscopy and analyzing the IR spectra.

Keywords: monoammonium salt of glycyrrhizic acid, glycyrrhizic acid, supramolecular complex, isomolar series, IR spectroscopy

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Authors: M. Shahina, K. Fakruddin, C. M. Subhan, S. Rangappa

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In this work, two mixtures with equal concentrations of 1) 4ꞌ-(6-(4-(pentylamino) methyl)-3-hydroxyphenoxy) hexyloxy) biphenyl-4-carbonitrile+-4-((4-(hexyloxy) benzylidene) amino) phenyl 4-butoxy benzoate and 2) 4ꞌ - (6-(4-(hexylamino) methyl)-3-hydroxyphenoxy) hexyloxy) biphenyl-4-carbonitrile+-4-((4-(octyloxy) benzylidene) amino) phenyl 4-butoxy benzoate, have been prepared. The transition temperature and optical texture are observed by using thermal microscopy. Density and birefringence studies are carried out on the above liquid crystalline mixtures. Using density and refractive indices data, the molecular polarizabilities are evaluated by using well-known Vuks and Neugebauer models. The molecular polarizability is also evaluated theoretically by Lippincott δ function model. The results reveal that the polarizability values are same in both experimental and theoretical methods.

Keywords: liquid crystals, optical textures, transition temperature, birefringence, polarizability

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Authors: Sadaf Moeez, Madiha Khalid, Zoya Khalid, Sania Shaheen, Sumbul Khalid

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Background: Inter-individual variation in response to metformin, which has been considered as a first line therapy for T2DM treatment is considerable. In the current study, it was aimed to investigate the impact of two genetic variants Leu125Phe (rs77474263) and Gly64Asp (rs77630697) in gene SLC47A1 on the clinical efficacy of metformin in T2DM Pakistani patients. Methods: The study included 800 T2DM patients (400 metformin responders and 400 metformin non-responders) along with 400 ethnically matched healthy individuals. The genotypes were determined by allele-specific polymerase chain reaction. In-silico analysis was done to confirm the effect of the two SNPs on the structure of genes. Association was statistically determined using SPSS software. Results: Minor allele frequency for rs77474263 and rs77630697 was 0.13 and 0.12. For SLC47A1 rs77474263 the homozygotes of one mutant allele ‘T’ (CT) of rs77474263 variant were fewer in metformin responders than metformin non-responders (29.2% vs. 35.5 %). Likewise, the efficacy was further reduced (7.2% vs. 4.0 %) in homozygotes of two copies of ‘T’ allele (TT). Remarkably, T2DM cases with two copies of allele ‘C’ (CC) had 2.11 times more probability to respond towards metformin monotherapy. For SLC47A1 rs77630697 the homozygotes of one mutant allele ‘A’ (GA) of rs77630697 variant were fewer in metformin responders than metformin non-responders (33.5% vs. 43.0 %). Likewise, the efficacy was further reduced (8.5% vs. 4.5%) in homozygotes of two copies of ‘A’ allele (AA). Remarkably, T2DM cases with two copies of allele ‘G’ (GG) had 2.41 times more probability to respond towards metformin monotherapy. In-silico analysis revealed that these two variants affect the structure and stability of their corresponding proteins. Conclusion: The present data suggest that SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) polymorphisms were associated with the therapeutic response of metformin in T2DM patients of Pakistan.

Keywords: diabetes, T2DM, SLC47A1, Pakistan, polymorphism

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Authors: Sumit Sharma, Rakesh Chandra, Pramod Kumar, Navin Kumar

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Molecular dynamics (MD) simulation has been used to study the effect of carbon nanofiber (CNF) volume fraction (Vf) and aspect ratio (l/d) on mechanical properties of CNF reinforced polypropylene (PP) composites. Materials Studio 5.5 has been used as a tool for finding the modulus and damping in composites. CNF composition in PP was varied by volume from 0 to 16%. Aspect ratio of CNF was varied from l/d=5 to l/d=100. To the best of the knowledge of the authors, till date there is no study, either experimental or analytical, which predict damping for CNF-PP composites at the nanoscale. Hence, this will be a valuable addition in the area of nanocomposites. Results show that with only 2% addition by volume of CNF in PP, E11 increases 748%. Increase in E22 is very less in comparison to the increase in E11. With increase in CNF aspect ratio (l/d) till l/d=60, the longitudinal loss factor (η11) decreases rapidly. Results of this study have been compared with those available in literature.

Keywords: carbon nanofiber, elasticity, mechanical properties, molecular dynamics

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Authors: Alya Harichane, Abderraouf Achour, Abdelbaki Benmounah

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The main difficulty encountered in the formulation of high-performance concrete (HPC) consists in choosing the most efficient cement-superplasticizer pair allowing to obtain maximum water reduction, good workability of the concrete in the fresh state, and very good mechanical resistance in the hardened state. The aim of this work is to test the efficiency of three polycarboxylate ether-based superplasticizers (PCE) marketed in Algeria with CEMI 52.5 R cement and to study the effect of chemical structure of PCE on zeta potential, rheological and mechanical properties of cement pastes. The property of the polymers in cement was tested by a Malvern Zetasizer 2000 apparatus and VT 550 viscometer. Results showed that the zeta potential and its rheological properties are related to the molecular weight and the density carboxylic of PCE. The PCE with a moderate molecular weight and the highest carboxylic groups had the best dispersion (high value of zeta potential) and lowest viscosity. The effect of the chemical structure of PCEs on mechanical properties is evaluated by the formulation of cement mortar with these PCEs. The result shows that there is a correlation between the zeta potential of polymer and the compressive strength of cement paste.

Keywords: molecular weight, polycarboxylate-ether superplasticizer, rheology, zeta potential

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Authors: Waqas Shafqat Chattha, Muhammad Iqbal, Amir Shakeel

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Transcriptional factors are proteins that play a vital role in regulating the transcription of target genes in different biological processes and are being widely studied in different plant species. In the current era of genomics, plant genomes sequencing has directed to the genome-wide identification, analyses and categorization of diverse transcription factor families and hence provide key insights into their structural as well as functional diversity. The DNA-binding with One Finger (DOF) proteins belongs to C2-C2-type zinc finger protein family. DOF proteins are plant-specific transcription factors implicated in diverse functions including seed maturation and germination, phytohormone signalling, light-mediated gene regulation, cotton-fiber elongation and responses of the plant to biotic as well as abiotic stresses. In this context, a genome-wide in-silico analysis of DOF TF family in diploid cotton species i.e. Gossypium raimondii has enabled us to identify 55 non-redundant genes encoding DOF proteins renamed as GrDofs (Gossypium raimondii Dof). Gene distribution studies have shown that all of the GrDof genes are unevenly distributed across 12 out of 13 G. raimondii chromosomes. The gene structure analysis illustrated that 34 out of 55 GrDof genes are intron-less while remaining 21 genes have a single intron. Protein sequence-based phylogenetic analysis of putative 55 GrDOFs has divided these proteins into 5 major groups with various paralogous gene pairs. Molecular evolutionary studies aided with the conserved domain as well as gene structure analysis suggested that segmental duplications were the principal contributors for the expansion of Dof genes in G. raimondii.

Keywords: diploid cotton , G. raimondii, phylogenetic analysis, transcription factor

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Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

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Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

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Authors: Chaudhari S. G., Saxena, S.

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We systematically and quantitatively investigated the effect of glucose as a model of natural molecular crowding agent on the structure and thermodynamics of Watson-Crick base paired three duplexes (named as D1, D2 and D3) of different base compositions and lengths. Structural analyses demonstrated that duplexes (D1 and D2) folded into B-form with different cations in the absence and presence of glucose while duplex (D3) folded into mixed A and B-form. Moreover, we demonstrated that the duplex was more stable in the absence of glucose, and marginally destabilized in its presence because glucose act as a weak structure breaker on the tetrahedral network of water. In the absence of glucose, the values of ΔG°25 for duplex (D1) were -13.56, -13.76, -12.46, and -12.36 kcal/mol, for duplex (D2) were -13.64, -12.93, -12.86, and -12.30 kcal/mol, for duplex (D3) were -10.05, -11.76, -9.91, -9.70 kcal/mol in the presence of Na+, K+, Na+ + Mg++ and K+ + Mg++ respectively. At high concentration of glucose (1:10000), there was increase in ΔG°25 for duplex (D1) -12.47, -12.37, -11.96, -11.55 kcal/mol, for duplex (D2) -12.37, -11.47, -11.98, -11.01 kcal/mol and for duplex (D3) -8.47, -9.17, -9.16, -8.66 kcal/mol. Our results provide the information that structure and stability of DNA duplex depends on the structure of molecular crowding agent present in its close vicinity. In this study, I have taken the hydration of simple sugar as an essential model for understanding interactions between hydrophilic groups and interfacial water molecules and its effect on hydrogen bonded DNA duplexes. On the basis of these relatively simple building blocks I hope to gain some insights for understanding more generally the properties of sugar–water–salt systems with DNA duplexes.

Keywords: natural molecular crowding, DNA Duplex, structure of DNA, bioengineering and life sciences

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Authors: Hyery Kang, Dong-Yeun Koh, Yun-Ho Ahn, Huen Lee

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Terahertz time-domain spectroscopy (THz-TDS) was used to observe the THF clathrate hydrate system with dosage of polyvinylpyrrolidone (PVP) with three different average molecular weights (10,000 g/mol, 40,000 g/mol, 360,000 g/mol). Distinct footprints of phase transition in the THz region (0.4 - 2.2 THz) were analyzed and absorption coefficients and complex refractive indices are obtained and compared in the temperature range of 253 K to 288 K. Along with the optical properties, ring breathing and stretching modes for different molecular weights of PVP in THF hydrate are analyzed by Raman spectroscopy.

Keywords: clathrate hydrate, terahertz, polyvinylpyrrolidone (PVP), THz-TDS, inhibitor

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Authors: R. Pilafkan, M. Kaffash Irzarahimi, S. F. Asbaghian Namin

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The biaxial buckling behavior of single-layered graphene sheets (SLGSs) is studied in the present work. To consider the size-effects in the analysis, Eringen’s nonlocal elasticity equations are incorporated into classical plate theory (CLPT). A Generalized Differential Quadrature Method (GDQM) approach is utilized and numerical solutions for the critical buckling loads are obtained. Then, molecular dynamics (MD) simulations are performed for a series of zigzag SLGSs with different side-lengths and with various boundary conditions, the results of which are matched with those obtained by the nonlocal plate model to numerical the appropriate values of nonlocal parameter relevant to each type of boundary conditions.

Keywords: biaxial buckling, single-layered graphene sheets, nonlocal elasticity, molecular dynamics simulation, classical plate theory

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Authors: Mahdi Golriz

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The aim of this work is to estimate the change in molecular structure of linear low-density polyethylene (LLDPE) during peroxide modification can be detected by a simple rheological method. For this purpose a commercial grade LLDPE (Exxon MobileTM LL4004EL) was reacted with different doses of dicumyl peroxide (DCP). The samples were analyzed by size-exclusion chromatography coupled with a light scattering detector. The dynamic shear oscillatory measurements showed a deviation of the δ-׀G ׀٭curve from that of the linear LLDPE, which can be attributed to the presence of long-chain branching (LCB). By the use of a simple rheological method that utilizes melt rheology, transformations in molecular architecture induced on an originally linear low density polyethylene during the early stages of reactive modification were indicated. Reasonable and consistent estimates are obtained, concerning the degree of LCB, the volume fraction of the various molecular species produced in peroxide modification of LLDPE.

Keywords: linear low-density polyethylene, peroxide modification, long-chain branching, rheological method

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Authors: Soraya Abtouche, Zeyneb Ghoualem, Syrine Daoudi, Lina Ouldmohamed, Xavier Assfeld

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This work reports density functional theory calculations of the optimized geometries, molecular reactivity, energy gap,and thermodynamic properties of the free base (H2P) and their Zn (II) metallated (ZnP), bearing one, two, or three carboxylic acid groups using the hybrid functional B3LYP, Cam-B3lYP, wb97xd with 6-31G(d,p) basis sets. When donating groups are attached to the molecular dye, the bond lengths are slightly decreased, which is important for the easy transfer of an electron from donating to the accepting group. For all dyes, the highest occupied molecular orbital/lowest occupied molecular orbital analysis results in positive outcomes upon electron injection to the semiconductor and subsequent dye regeneration by the electrolyte. The ionization potential increases with increasing conjugation; therefore, the compound dye attached to one carboxylic acid group has the highest ionization potential. The results show higher efficiencies of those sensitized with ZnP. These results have been explained, taking into account the electronic character of the metal ion, which acts as a mediator in the injection step, and, on the other hand, considering the number of anchoring groups to which it binds to the surface of TiO2.

Keywords: DSSC, porphyrin, TD-DFT, electronic properties, donor-acceptor groups

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Authors: Amir Doustgani

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Melt electrospinning is a safe and simple technique for the production of micro and nanofibers which can be an alternative to conventional solvent electrospinning. The effects of various melt-electrospinning parameters, including molecular weight, electric field strength, flow rate and temperature on the morphology and fiber diameter of polylactic acid were studied. It was shown that molecular weight was the predominant factor in determining the obtainable fiber diameter of the collected fibers. An orthogonal design was used to examine process parameters. Results showed that molecular weight is the most effective parameter on the average fiber diameter of melt electrospun PLA nanofibers and the flow rate has the less important impact. Mean fiber diameter increased by increasing MW and flow rate, but decreased by increasing electric field strength and temperature. MFD of optimized fibers was below 100 nm and the result of software was in good agreement with the experimental condition.

Keywords: fiber formation, processing, spinning, melt blowing

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Authors: Mohammad Hossein Modarressi, Mozhgan Mondeali, Khabat Barkhordari, Ali Etemadi

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The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant concerns worldwide due to its catastrophic effects on public health. The SARS-CoV-2 infection is initiated with the binding of the receptor-binding domain (RBD) in its spike protein to the ACE2 receptor in the host cell membrane. Due to the error-prone entity of the viral RNA-dependent polymerase complex, the virus genome, including the coding region for the RBD, acquires new mutations, leading to the appearance of multiple variants. These variants can potentially impact transmission, virulence, antigenicity and evasive immune properties. S477N mutation located in the RBD has been observed in the SARS-CoV-2 omicron (B.1.1. 529) variant. In this study, we investigated the consequences of S477N mutation at the molecular level using computational approaches such as molecular dynamics simulation, protein-protein interaction analysis, immunoinformatics and free energy computation. We showed that displacement of Ser with Asn increases the stability of the spike protein and its affinity to ACE2 and thus increases the transmission potential of the virus. This mutation changes the folding and secondary structure of the spike protein. Also, it reduces antibody neutralization, raising concern about re-infection, vaccine breakthrough and therapeutic values.

Keywords: S477N, COVID-19, molecular dynamic, SARS-COV2 mutations

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Authors: Neha Kanodia, M. Kamil

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Properties of mono layers of Pluronic F127 at air/water interface have been investigated by using Langmuir trough method. Pluronic F127 is a triblock copolymer of poly (ethyleneoxide) (PEO groups)– poly (propylene oxide) (PO groups)–poly(ethylene oxide) (PEO groups). Surface pressure versus mean molecular area isotherms is studied. The isotherm of the mono layer showed the characteristics of a pancake-to-brush transition upon compression of the mono layer. The effect of adding surfactant (SDS) to polymer and the effect of increasing loading on polymer was also studied. The effect of repeated compression and expansion cycle (or hysteresis curve) is investigated to know about stability of the film formed. Static elasticity of mono layer gives information about molecular arrangement, phase structure and phase transition.

Keywords: surface-pressure, mean molecular area isotherms, hysteresis, static elasticity

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Authors: Jie Lin, Yiwen Pan, Li Zhang, Zhangyong Xia

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Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, immune cells, and extracellular matrix in the arterial walls. This pathological process can lead to the formation of plaques that can obstruct blood flow and trigger various cardiovascular diseases such as heart attack and stroke. The underlying molecular mechanisms still remain unclear, although many studies revealed the dysfunction of endothelial cells, recruitment and activation of monocytes and macrophages, and the production of pro-inflammatory cytokines and chemokines in atherosclerosis. This study aimed to identify hub genes involved in the progression of atherosclerosis and to analyze their biological function in silico, thereby enhancing our understanding of the disease’s molecular mechanisms. Through the analysis of microarray data, we examined the gene expression in media and neo-intima from plaques, as well as distant macroscopically intact tissue, across a cohort of 32 hypertensive patients. Initially, 112 differentially expressed genes (DEGs) were identified. Subsequent immune infiltration analysis indicated a predominant presence of 27 immune cell types in the atherosclerosis group, particularly noting an increase in monocytes and macrophages. In the Weighted gene co-expression network analysis (WGCNA), 10 modules with a minimum of 30 genes were defined as key modules, with blue, dark, Oliver green and sky-blue modules being the most significant. These modules corresponded respectively to monocyte, activated B cell, and activated CD4 T cell gene patterns, revealing a strong morphological-genetic correlation. From these three gene patterns (modules morphology), a total of 2509 key genes (Gene Significance >0.2, module membership>0.8) were extracted. Six hub genes (CD36, DPP4, HMOX1, PLA2G7, PLN2, and ACADL) were then identified by intersecting 2509 key genes, 102 DEGs with lipid-related genes from the Genecard database. The bio-functional analysis of six hub genes was estimated by a robust classifier with an area under the curve (AUC) of 0.873 in the ROC plot, indicating excellent efficacy in differentiating between the disease and control group. Moreover, PCA visualization demonstrated clear separation between the groups based on these six hub genes, suggesting their potential utility as classification features in predictive models. Protein-protein interaction (PPI) analysis highlighted DPP4 as the most interconnected gene. Within the constructed key gene-drug network, 462 drugs were predicted, with ursodeoxycholic acid (UDCA) being identified as a potential therapeutic agent for modulating DPP4 expression. In summary, our study identified critical hub genes implicated in the progression of atherosclerosis through comprehensive bioinformatic analyses. These findings not only advance our understanding of the disease but also pave the way for applying similar analytical frameworks and predictive models to other diseases, thereby broadening the potential for clinical applications and therapeutic discoveries.

Keywords: atherosclerosis, hub genes, drug prediction, bioinformatics

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Authors: Rozhgar A. Khailany, Mehri Igci, Emine Bayraktar, Sakip Erturhan, Metin Karakok, Ahmet Arslan

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Kidney cancer is the most lethal urological cancer accounting for 3% of adult malignancies. VHL, a tumor-suppressor gene, is best known to be associated with renal cell carcinoma (RCC). The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The PBRM1 gene encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes. SETD2 encodes a histone methyltransferase, which may play a role in suppressing tumor development. In this study, RNAs of 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were examined by RT-PCR, SSCP and sequencing techniques. VHL, PBRM1 and SETD2 expressions were relatively down-regulated. However, statistically no significance was found (Wilcoxon signed rank test, p > 0.05). Interestingly, no mutation was observed on the contrary of previous studies. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Further analysis is required to identify the responsible genes rather than VHL, PBRM1 and SETD2 in kidney cancer.

Keywords: kidney cancer, molecular biomarker, expression analysis, mutation screening

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

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

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

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Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

Abstract:

Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

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Authors: Nahush Modak, Meena Pangarkar, Anand Pathak, Ankita Tamhane

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Background: Breast cancer is the prominent cause of cancer and mortality among women. This study was done to show the statistical analysis of a cohort of over 250 patients detected with breast cancer diagnosed by oncologists using Immunohistochemistry (IHC). IHC was performed by using ER; PR; HER2; Ki-67 antibodies. Materials and methods: Formalin fixed Paraffin embedded tissue samples were obtained by surgical manner and standard protocol was followed for fixation, grossing, tissue processing, embedding, cutting and IHC. The Ventana Benchmark XT machine was used for automated IHC of the samples. Antibodies used were supplied by F. Hoffmann-La Roche Ltd. Statistical analysis was performed by using SPSS for windows. Statistical tests performed were chi-squared test and Correlation tests with p<.01. The raw data was collected and provided by National Cancer Insitute, Jamtha, India. Result: Luminal B was the most prevailing molecular subtype of Breast cancer at our institute. Chi squared test of homogeneity was performed to find equality in distribution and Luminal B was the most prevalent molecular subtype. The worse prognostic indicator for breast cancer depends upon expression of Ki-67 and her2 protein in cancerous cells. Our study was done at p <.01 and significant dependence was observed. There exists no dependence of age on molecular subtype of breast cancer. Similarly, age is an independent variable while considering Ki-67 expression. Chi square test performed on Human epidermal growth factor receptor 2 (HER2) statuses of patients and strong dependence was observed in percentage of Ki-67 expression and Her2 (+/-) character which shows that, value of Ki depends upon Her2 expression in cancerous cells (p<.01). Surprisingly, dependence was observed in case of Ki-67 and Pr, at p <.01. This shows that Progesterone receptor proteins (PR) are over-expressed when there is an elevation in expression of Ki-67 protein. Conclusion: We conclude from that Luminal B is the most prevalent molecular subtype at National Cancer Institute, Jamtha, India. There was found no significant correlation between age and Ki-67 expression in any molecular subtype. And no dependence or correlation exists between patients’ age and molecular subtype. We also found that, when the diagnosis is Luminal A, out of the cohort of 257 patients, no patient shows >14% Ki-67 value. Statistically, extremely significant values were observed for dependence of PR+Her2- and PR-Her2+ scores on Ki-67 expression. (p<.01). Her2 is an important prognostic factor in breast cancer. Chi squared test for Her2 and Ki-67 shows that the expression of Ki depends upon Her2 statuses. Moreover, Ki-67 cannot be used as a standalone prognostic factor for determining breast cancer.

Keywords: breast cancer molecular subtypes , correlation, immunohistochemistry, Ki-67 and HR, statistical analysis

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Authors: Manar Makhoul, Buthainah Alsalamah, Salam Lawand, Hassan Azzam

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The major storage proteins in endosperm of 33 cultivated and wild barley genotypes (H.vulgare, H. spontaneum, H. bulbosum, H. murinum, H. marinum) were analyzed to demonstrate the variation in the hordein polypeptides encoded by multigene families in grains. The SDS-PAGE revealed 13 and 17 alleles at the Hor1 and the Hor2 loci respectively, with frequencies from 0.83 to 14 and 0.56 to 13.41% respectively, while seven alleles at the Hor3 locus with frequencies from 3.63 to 30.91% were recognized. The phylogenetic analysis indicated to relevance of the polymorphism in hordein patterns as successful tool in identifying the individual genotypes and discriminating the species according to genome type. We also reported in this research complete nucleotide sequence B-hordein genes of seven wild and cultivated barley genotypes. A 152bp upstream sequence of B-hordein promoter contained a TATA box, CATC box, AAAG motif, N-motif and E-motif. In silico analysis of B-Hordein sequences demonstrated that the coding regions were not interrupted by any intron, and included the complete ORF which varied between 882 and 906 bp, and encoded mature proteins with 293-301 residues characterized by high contents of glutamine (29%), and proline (18%). Comparison of the predicted polypeptide sequences with the published ones suggested that all S-rich prolamins genes are descended from common ancestor. The sequence started at N-terminal with a signal peptide, and then followed directly by two domains; a repetitive one based on the repetition of the repeat unit PQQPFPQQ and C-terminal domain. Also, it was found that positions of the eight cysteine residues were highly conserved in all the B-hordein sequences, but Hordeum bulbosum had additional unpaired one. The phylogenetic tree of B-hordein polypeptide separated the genotypes in distinct seven subgroups. In general, the high homology between B-hordeins and LMW glutenin subunits suggests similar bread-making influences for these B-hordeins.

Keywords: hordeum, phylogenetic tree, sequencing, storage protein

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Authors: Murali Aarthy, Sanjeev Kumar Singh

Abstract:

High risk human papillomaviruses are highly associated with the carcinoma of the cervix and the other genital tumors. Cervical cancer develops through the multistep process in which increasingly severe premalignant dysplastic lesions called cervical intraepithelial neoplastic progress to invasive cancer. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers drives the cells into S-phase creating an environment conducive for viral genome replication and cell proliferation. The replication of the virus occurs in the terminally differentiating epithelium and requires the activation of cellular DNA replication proteins. To date, no suitable drug molecule is available to treat HPV infection whereas identification of potential drug targets and development of novel anti-HPV chemotherapies with unique mode of actions are expected. Hence, our present study aimed to identify the potential inhibitors analogous to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems. A 3D similarity search on the natural small molecule library from natural product database using EGCG identified 11 potential hits based on their similarity score. The structure based docking strategies were implemented in the potential hits and the key interacting residues of protein with compounds were identified through simulation studies and binding free energy calculations. The conformational changes between the apoprotein and the complex were analyzed with the simulation and the results demonstrated that the dynamical and structural effects observed in the protein were induced by the compounds and indicated the dominance to the oncoprotein. Overall, our study provides the basis for the structural insights of the identified potential hits and EGCG and hence, the analogous compounds identified can be potent inhibitors against the HPV 16 E7 oncoprotein.

Keywords: EGCG, oncoprotein, molecular dynamics simulation, analogues

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Authors: Shokofeh Ebrtahimi

Abstract:

Let G be the chemical graph of a molecule. The matrix D = [dij ] is called the detour matrix of G, if dij is the length of longest path between atoms i and j. The sum of all entries above the main diagonal of D is called the detour index of G.Chemical graph theory is the topology branch of mathematical chemistry which applies graph theory to mathematical modelling of chemical phenomena.[1] The pioneers of the chemical graph theory are Alexandru Balaban, Ante Graovac, Ivan Gutman, Haruo Hosoya, Milan Randić and Nenad TrinajstićLet G be the chemical graph of a molecule. The matrix D = [dij ] is called the detour matrix of G, if dij is the length of longest path between atoms i and j. The sum of all entries above the main diagonal of D is called the detour index of G. In this paper, a new program for computing the detour index of molecular graphs of nanotubes by heptagons is determineded. Some Conjectures about detour index of Molecular graphs of nanotubes is included.

Keywords: chemical graph, detour matrix, Detour index, carbon nanotube

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Authors: A. Didaoui, N. Benhalima, M. Elkeurti, A. Chouaih, F. Hamzaoui

Abstract:

The monomer and dimer structures of the title molecule have been obtained from density functional theory (DFT) B3LYP method with 6-31G (d,p) as basis set calculations. The optimized geometrical parameters obtained by B3LYP/6-31G (d,p) method show good agreement with xperimental X-ray data. The polarizability and first order hyperpolarizabilty of the title molecule were calculated and interpreted. the intermolecular N–H•••O hydrogen bonds are discussed in dimer structure of the molecule. The vibrational wave numbers and their assignments were examined theoretically using the Gaussian 03 set of quantum chemistry codes. The predicted frontier molecular orbital energies at B3LYP/6-31G(d,p) method set show that charge transfer occurs within the molecule. The frontier molecular orbital calculations clearly show the inverse relationship of HOMO–LUMO gap with the total static hyperpolarizability. The results also show that N-(2-Methylphenyl)-2-nitrobenzenesulfonamide molecule may have nonlinear optical (NLO) comportment with non-zero values.

Keywords: DFT, Gaussian 03, NLO, N-(2-Methylphenyl)-2-nitrobenzenesulfonamide

Procedia PDF Downloads 525