6 results
Search Results
Now showing 1 - 6 of 6
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 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 Embargo Comparative Study of the Characteristics of Nano Silica-, Silica Fume- and Fly Ash-Incorporated Cement Mortars(Univ Fed Sao Carlos, Dept Engenharia Materials, Laboratoria De Materiais Vitreos, Caixa Postal 676, Sao Carlos, 13565-905Sp, Brazil, 2014) Biricik, Hasan; SARIER, NİHAL; 58815; 114920The structural characteristics of cement mortars, impregnated with nano silica (NS), silica fume (SF) and fly ash (FA), were comparatively studied using Fourier transform infrared spectrometer (FTIR), thermogravimeter-differential thermogravimeter (TG-DTG) and scanning electron microscope (SEM). The mechanical strengths of the specimens were determined at early (7th day) and standard (28th day) curing ages. The compressive strengths and flexural strengths developed in the mortar specimens containing NS particles were found considerably higher than those of the corresponding specimens of SF and FA over and above the control at both ages. FTIR, TG-DTG and SEM analyses results were consistent with the remarkable increase in the mechanical strength of the mortars with NS. These increases in the strengths of the mortars with NS are attributable to the nano sized particles and extensive surface area of NS. The nano sized particles, as nucleating agents, promoted the hydration of C3S and C2S and the formation of C-S-H phase. Plenty of active sites on the surface of NS particles induced their pozzolanic reactivity and the extent of bond formation between NS particles and free CH.Publication Open Access Indigo Carmine Binding to Cu(II) in Aqueous Solution and Solid State: Full Structural Characterization Using NMR, FTIR and UV/Vis Spectroscopies and DFT Calculations(MDPI, 2024) Braz, Sofia; Justino, Licinia L. G.; Ramos, M. Luisa; FAUSTO, RUIThe food industry uses indigo carmine (IC) extensively as a blue colorant to make processed food for young children and the general population more attractive. Given that IC can act as a ligand, this raises concerns about its interactions with essential metal ions in the human body. In view of this interest, in the present investigation, the copper(II)/indigo carmine system was thoroughly investigated in aqueous solution and in the solid state, and the detailed structural characterization of the complexes formed between copper(II) and the ligand was performed using spectroscopic methods, complemented with DFT and TD-DFT calculations. NMR and UV/Vis absorption spectroscopy studies of the ligand in the presence of copper(II) show changes that clearly reveal strong complexation. The results point to the formation of complexes of 1:1, 1:2 and 2:1 Cu(II)/IC stoichiometry in aqueous solution, favored in the pH range 6-10 and stable over time. DFT calculations indicate that the coordination of the ligand to the metal occurs through the adjacent carbonyl and amine groups and that the 1:1 and the 2:1 complexes have distorted tetrahedral metal centers, while the 1:2 structure is five-coordinate with a square pyramidal geometry. FTIR results, together with EDS data and DFT calculations, established that the complex obtained in the solid state likely consists of a polymeric arrangement involving repetition of the 1:2 complex unit. These results are relevant in the context of the study of the toxicity of IC and provide crucial data for future studies of its physiological effects. Although the general population does not normally exceed the maximum recommended daily intake, young children are highly exposed to products containing IC and can easily exceed the recommended dose. It is, therefore, extremely important to understand the interactions between the dye and the various metal ions present in the human body, copper(II) being one of the most relevant due to its essential nature and, as shown in this article, the high stability of the complexes it forms with IC at physiological pH.