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Publication Restricted Shedding Light Into the Biological Activity of Aminopterin, Via Molecular Structural, Docking, and Molecular Dynamics Analyses(Taylor & Francis Inc., 2023) Çelik, Sefa; YILMAZ, GÖZDE; AKYÜZ, SEVİM; Özel, Ayşen E.In this study, the structural and anticancer properties of aminopterin, as well as its antiviral characteristics, were elucidated. The preferred conformations of the title molecule were investigated with semiempirical AM1 method, and the obtained the lowest energy conformer was then optimized by using density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. The vibrational frequencies of the optimized structure were calculated by the same level of theory and were compared with the experimental values. The vibrational assignments were performed based on the computed potential energy distribution (PED) of the vibrational modes. The molecular electrostatic potential (MEP) and frontier molecular orbitals (HOMO, LUMO) analyses were carried out for the optimized structure and the chemical reactivity has been scrutinized. To enlighten the biological activity of aminopterin as anticancer and anti-COVID-19 agents, aminopterin was docked into DNA, & alpha;(IIB)& beta;(3) and & alpha;(5)& beta;(1)integrins, human dihydrofolate reductase, main protease (M-pro) of SARS-CoV-2 and SARS-CoV-2/ACE2 complex receptor. The binding mechanisms of aminopterin with the receptors were clarified. The molecular docking results revealed the strong interaction of the aminopterin with DNA (-8.2 kcal/mol), & alpha;(IIB)& beta;(3) and & alpha;(5)& beta;(1) integrins (-9.0 and -10.8 kcal/mol, respectively), human dihydrofolate reductase (-9.7 kcal/mol), M-pro of SARS-CoV-2 (-6.7 kcal/mol), and SARS-CoV-2/ACE2 complex receptor (-8.1 kcal/mol). Moreover, after molecular docking calculations, top-scoring ligand-receptor complexes of the aminopterin with SARS-CoV-2 enzymes (6M03 and 6M0J) were subjected to 50 ns all-atom MD simulations to investigate the ligand-receptor interactions in more detail, and to determine the binding free energies accurately. The predicted results indicate that the aminopterin may significantly inhibit SARS-CoV-2 infection. Thus, in this study, as both anticancer and anti-COVID-19 agents, the versatility of the biological activity of aminopterin was shown.Publication Metadata only Vibrational spectroscopic and structural investigations of bioactive molecule Glycyl-Tyrosine (Gly-Tyr)(Elsevier Science Bv, Po Box 211, 1000 AE Amsterdam, Netherlands, 2017-09) Çelik, Sefa; Özel, Ayşen E.; AKYÜZ, SEVİM; 110147; 10127; 110745This study investigated the conformational behavior of biological active molecule Glycyl-Tyrosine (Gly-Tyr) dipeptide and its dimers, by Boltzmann jump and DET calculations. The energy calculations on Gly-Tyr dipeptide as a function of side chain torsion angles enabled us to determine the preferred conformations. The most stable conformations obtained from the above process were further optimized by the DFT calculations. The geometry optimization and vibrational wavenumbers calculations of Gly-Tyr dipeptide were carried out with the Gaussian03 program by using density functional theory (DFF) with B3LYP functional and 6-31++G (d,p) basis set. The dimeric forms of the dipeptide were also formed and energetically preferred conformations of dimers were investigated using the same method and the same basis set. The results provided a good account of the role of the number and type of inter- or/and intramolecular H-bond interactions existing in the dialer and monomer forms of the dipeptides. The fundamental vibrational wavenumbers, IR and Raman intensities for the optimized structure of monomeric and dimeric forms of the dipeptide were calculated and compared with the experimental vibrational spectra of solid Gly-Tyr dipeptide. Vibrational assignment of the molecule was done using the potential energy distribution analysis. HOMO-LUMO energy has been used to elucidate the reasons for intra molecular charge transfer. (C) 2017 Elsevier B.V. All rights reserved.Publication Open Access Evaluation of Anti-Cancer and Anti-Covid-19 Properties of Cationic Pentapeptide Glu-Gln-Arg-Pro-Arg, From Rice Bran Protein and Its D-Isomer Analogs Through Molecular Docking Simulations(Elsevier Science Inc., 2021) Gasymov, Oktay K.; Çelik, Sefa; Ağaeva, Gülşen; AKYÜZ, SEVİM; Keçel-Gündüz, Serda; Qocayev, Niftali M.; Özel, Ayşen E.; Ağaeva, Ülker; Bakhishova, Matanat; Aliyev, Jamil A.Bioactive peptides derived from food proteins are becoming increasingly popular due to the growing awareness of their health-promoting properties. The structure and mechanism of anti-cancer action of pentapeptide GluGln-Arg-Pro-Arg (EQRPR) derived from a rice bran protein are not known. Theoretical and experimental methods were employed to fill this gap. The conformation analysis of the EQRPR pentapeptide was performed first and the obtained lowest energy conformer was optimized. The experimental structural data obtained by FTIR and CD spectroscopies agree well with the theoretical results. D-isomer introduced one-by-one to each position and all D-isomers of the peptide were also examined for its possible anti-proteolytic and activity enhancement properties. The molecular docking revealed avid binding of the pentapeptide to the integrins alpha(5)beta(1) and alpha(IIb)beta(3), with K-d values of 90 nM and 180 nM, respectively. Moreover, the EQRPR and its D-isomers showed strong binding affinities to apo-and holo-forms of M-pro, spike glycoprotein, ACE2, and dACE2. The predicted results indicate that the pentapeptide may significantly inhibit SARS-CoV-2 infection. Thus, the peptide has the potential to be the leading molecule in the drug discovery process as having multifunctional with diverse biological activities.Publication Restricted Vibrational Spectroscopic Characterization and Structural Investigations of Cepharanthine, a Natural Alkaloid(Elsevier, 2022) Çelik, Sefa; AKYÜZ, SEVİM; Özel, Ayşen E.Cepharanthine, a natural alkaloid obtained from the Stephania cepharantha Hayata plant, that has anti-tumor, anti-inflammatory, antioxidative, antiparasitic, and antiviral properties, has been widely used for many years to treat a wide variety of diseases in Japan. However, to elucidate its mechanism of action needs further study. This study aimed to enlighten the molecular structure, and the anticancer and antiviral action mechanisms of Cepharanthine. To evaluate the molecular structure of Cepharanthine, conforma-tional analysis was performed using the DFT/B3LYP with 6-31G(d,p) basis set. The obtained most stable molecular geometry was then optimized at the DFT/B3LYP/6-311 ++ G(d,p) level of theory. The observed IR and Raman bands were compared with harmonic vibrational frequencies of the optimized structure of cepharanthine, calculated using the same level of theory, and assigned on the base of potential energy distribution (PED). The experimental UV-Vis absorption spectrum was recorded and compared with the simulated Time Dependent (TD-DFT/B3LYP/6-311 ++ G(d,p)) method. Moreover, (1) H and C-13 NMR spectra has been calculated and compared by the experimental spectra. To reveal pharmacological importance of Cepharanthine, a molecular docking study was performed with NF-kappa B (nuclear factor kappa-light-chain-enhancer of activated B cells) receptor which controls transcription of DNA, cytokine production and cell survival. Molecular docking simulations revealed that Cepharanthine showed strong binding affinity to NF-kappa B receptor ( Delta G = -8.9 kcal/mol). In addition, to enlight the antiviral properties of cepharantine and to explore the possibility of its use in the treatment of COVID-19, the interactions of cepharanthine with ACE2, apo and holo forms of COVID-19 main protease enzyme (M-pro) and spike glycoprotein of SARSCoV-2 receptors were investigated. (c) 2022 Elsevier B.V. All rights reserved.Publication Restricted Vibrational Spectroscopic Characterization, Quantum Chemical and Molecular Docking Studies of Valyl-Methionine Dipeptide(Taylor & Francis Inc., 2020) Çelik, Sefa; E. Özel, Ayşen; Durak, Volkan; AKYÜZ, SEVİMIn this study, valyl-methionine dipeptide (Val-Met), a breakdown product of protein digestion or protein catabolism,has been investigated both theoretically and experimentally. Four different valyl-methionine conformations were formed, using the geometric parameters of two asymmetric units of L-Valine and L-Methionine, taken from the literature and their optimized geometric parameters were obtained by DFT/B3LYP level of theory, using different basis sets. The vibrational spectral analysis for the obtained two energetically most stable conformations were carried out theoretically by using 6-311++G(d,p) basis set. Experimental vibrational spectra of the title molecule were compared with the calculated spectra and the vibrational modes were assigned on the basis of potential energy distributions (PED) analysis, performed using the MOLVIB program. Furthermore, molecular electrostatic potential map analysis was carried out and dipole moment of the compound was calculated. Conformation analysis is an important step in molecular modeling. The selection of suitable conformers for many flexible drug molecules, which can be present in many conformations by turning around single bonds, to adopt different conformations, can easily be overlooked. In this work a series of dipeptide with A and B forms of valine and methionine amino acids have been chosen as examples to demonstrate the importance of conformational analysis. Energy differences between conformations underline the importance of a detailed conformational analysis and should be taken into account when defining their activities. Results show that the formation of hydrogen bonds between N1 and H17 and between H17 and O25 in Valyl(B)-Methionine(B) dipeptide, affects the stability of the molecule. The molecular electrostatic potential of the title molecule has also been calculated which is a very useful property in prediction of molecular reactive behavior. In addition, in silico molecular docking studies were performed for the title molecule with DNA. The results indicated the ability of the Val-Met dipeptide to bind DNA.Publication Metadata only Enez Kazısından Çıkartılan Bazı Arkeolojik Seramik ve Killerin FTIR, Mikro-Raman, EDXRF, XRD ve Kemometrik Yöntemler ile Analizi(2019-09) Çelik, Sefa; E.Özel, Ayşen; Başaran, Sait; AKYÜZ, SEVİM; 10127; 110147; 110745Potteries are the most abundant findings among the archeological artifacts. These findings, whose main raw material is clay, give important information about the civilization, culture, technology and trade of that period. Clay minerals undergo chemical and structural changes during the firing; e.g. during thermal treatment the structural collapse due to loss of structural hydroxyls, transformation to different mineral structures due to reaction with calcite in the structure and phase changes. For this reason, investigation of the mineral structures of the ancient potteries gives information about the firing temperature and firing conditions. Since XRD provides information mineral phases only in crystalline state, in combination to XRD the FTIR and Raman spectroscopic investigations and the determination of elemental contents by EDXRF allow us to determine the firing- temperature and -conditions in more detail. In this study, pottery fragments belonging to 4th-6th century BC, excavated in Enez- Turkey, were analyzed by different analytical techniques, in comparison with those of the local clays unearthed during the excavations. The firing temperatures and firing conditions were estimated. The XRD analysis of the raw clay found in the excavation area showed that it contained montmorillonite, illite and muscovite. The comparative FTIR and micro-Raman spectroscopic, EDXRF and XRD analyzes of the terracotta remains allowed to determine the chemical and mineralogical contents of the ceramic fragments. Moreover, chemometric techniques were applied on FTIR results in order to determine similarities and dissimilarities between archaeological findings and to reveal the distinct groups. Principal component analysis and cluster analysis techniques were used.