Sefa Celik

Lipopeptides are natural molecules with amphiphilic properties that exhibit various biological activities due to their lipid and peptide components. In this study, the structural, electronic, and vibrational properties of C16-Glu-Gln-Arg-Pro-Arg (C16-EQRPR), a newly synthesized lipopentapeptide formed by attaching palmitic acid to the N-terminus of the pentapeptide, were analyzed. Additionally, its antiviral and anticancer properties were evaluated through molecular docking studies. First, conformational analysis of C16-EQRPR was performed using the MMFF molecular mechanics method, and the lowest-energy conformer obtained was then optimized using DFT/wb97xd/6-31G(d,p) level of theory. The geometric parameters of the optimized structure were reported. Vibrational frequencies were calculated using the same level of theory and compared with experimental results. Complete vibrational assignments were made based on the potential energy distribution (PED) of the vibrational modes. Molecular electrostatic potential (MEP) analysis was performed for the optimized structure. The anticancer and antiviral effects of the lipopeptide were computationally assessed through molecular docking simulations of C16-EQRPR binding to the active sites of various targets, including B-DNA, ACE2, integrins (α₅β₃, α_IIBβ₃, and α₅β₁), human serum albumin, EGFR, FYN, and apo, as well as the holo forms of SARS-CoV-2 M^Pro and SARS-CoV-2 spike glycoprotein. Following molecular docking calculations, the interaction of lipopentapeptide with integrin α₅β₁(PDB ID: 4WK0) was analyzed in detail using molecular dynamics simulations. This study aims to characterize the molecular and biological features of the C16-EQRPR lipopeptide, highlighting its potential as both an anticancer and antiviral agent. However, experimental validation of these findings remains required.

1. Piperazine substituted compounds have attracted great attention for synthetic chemists for their importance in drug design as they show antibacterial activities against a wide variety of pathoge...

In this study, we present detailed results on the molecular structure, vibrational frequencies, and bioactivity of the neutral L‐Glu‐L‐Gln‐L‐Arg‐L‐Pro‐L‐Arg (EQRPR) pentapeptide, derived from rice bran, which exhibits anti‐cancer, anti‐Alzheimer's, and anti‐obesity properties. Theoretical conformational analysis was performed to evaluate the conformational preferences of the pentapeptide. The most stable conformer was then optimized at the DFT/b3lyp/6–31G(d,p), DFT/b3lyp/6–31 + G(d,p), and DFT/wb97xd/6–31++G(d,p) levels of theory. The experimental FTIR and Raman spectra were compared with the theoretically predicted vibrational spectra at these levels. As the DFT/wb97xd/6–31++G(d,p) results showed the closest agreement with the experimental data, all subsequent calculations were performed using this level of theory. The molecular electrostatic potential (MEP) and frontier molecular orbitals were calculated using the optimized pentapeptide structure to evaluate its chemical reactivity. To investigate its potential biological activity as an anticancer and antiviral agent, molecular docking studies were performed against 1BNA, 4HJO, 1JV2, 3ZDX, 4WK0, 6 M03, 6 LU7, and 6VXX targets. Among these, the EQRPR pentapeptide exhibited the strongest binding affinity toward α ₅ β ₁ integrin (4WK0; ∆ G = −9.3 kcal/mol). Furthermore, following the docking calculations, the best conformation of the EQRPR‐ α ₅ β ₁ integrin complex was subjected to 200 ns of all‐atom molecular dynamics simulations. The MD results indicate the stability of the EQRPR‐4WK0 complex, and the binding free energy was determined from the simulation results using the Molecular Mechanics/Poisson‐Boltzmann Surface Area (MM‐PBSA) method as −72.9895 kcal/mol. Overall, these results suggest that the neutral EQRPR pentapeptide possesses broad therapeutic potential and may serve as a promising candidate for the development of antiviral and anticancer agents.

1. Human serum albumin (HSA) is an abundant and versatile protein in plasma and interstitial fluids. It is the primary plasma carrier protein, binding and transporting a wide variety of biologicall...

Thymocartin, also known as Thymopoietin II (32–35), is a tetrapeptide fragment (Arg-Lys-Asp-Val) of thymopoietin with immunomodulatory properties. In this study, thymocartin was thoroughly examined for its structural features and antibacterial, antiviral, and anticancer activities. Conformational analysis was performed to investigate its conformational preferences and better understand its biological activity. The most stable conformer identified was optimized using density functional theory (DFT) at the B3LYP/6-311++G(d,p) level. The vibrational wavenumbers of the optimized structure were calculated and compared with experimental data to evaluate the accuracy of the computational structure. The potential of thymocartin as an anticancer agent was explored through molecular docking simulations with E. coli DNA Gyrase B (PDB ID: 6F86) and the epidermal growth factor receptor (EGFR; PDB ID: 4HJO). Following molecular docking, 200 ns all-atom molecular dynamics (MD) simulations were conducted on the top-scoring ligand-receptor complexes involving 4HJO and 6F86, providing further insight into ligand-receptor interactions. Overall, thymocartin showed diverse biological activities, especially antibacterial and anticancer effects. KEY WORDS: Thymopoietin II (32–35), Thymocartin, DFT calculations, Vibrational analysis, Molecular Docking, Molecular dynamics Bull. Chem. Soc. Ethiop. 2026, 40(2), 319-339 DOI: https://dx.doi.org/10.4314/bcse.v40i2.5

Two new anthraquinone derivatives: 1-(4-ethylpiperazin-1-yl)-5-chloroanthracene-9,10-dione and 1-(4-methylpiperidine-1-yl)-5-chloroanhtrecene-9,10-dione were synthesized in the laboratory and their structures were confirmed by Fourier transform-infrared and nuclear magnetic resonance techniques. The optimal molecular geometry was determined using a 6-311+G(d,p) basis set and the Density Functional Theory, B3LYP approach. The presence of charge transfer within the molecule was demonstrated by the energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). These new anthraquinone derivatives exhibited antibacterial activity against both Gram-positive and Gram-negative bacteria. The highest antimicrobial effect was observed against Gram-positive bacteria, especially Bacillus cereus and Staphylococcus aureus. The antibacterial properties of these new anthraquinone derivatives were also demonstrated by molecular docking simulations using Escherichia coli DNA gyrase B (PDB ID: 6F86). Moreover, molecular dynamics (MD) simulations conducted over a 100 ns period verified that the 1-(4-ethylpiperazin-1-yl)-5-chloroanthracene-9,10-dione-6F86 and 1-(4-methylpiperidine-1-yl)-5-chloroanhtrecene-9,10-dione-6F86 complexes were stable. According to a combination of experimental, computational, and biological research, compounds are promising antibacterial agents that might be developed further.

To gain deeper insights into the biological activity of thymopentin, its structural, anticancer, antiviral and antimicrobial properties were systematically investigated. Conformational preferences of thymopentin were investigated through conformational analysis and the lowest energy conformation was optimized using density functional theory (DFT) method, Becke three Lee–Yang–Parr (B3LYP) functional and 6-31G(d,p) basis set. Vibrational wavenumbers of the optimized structure were computed and compared with the experimental results. To elucidate the potential of thymopentin as anti-COVID-19 and anticancer agents, molecular docking simulations were performed. Thymopentin was docked into DNA (PDB ID: 1BNA), SARS-CoV-2 main protease (PDB ID: 6M03) and EGFR receptor complex (PDB ID: 4HJO). Additionally, following molecular docking analyses, top-scoring ligand-receptor complexes of thymopentin with SARS-CoV-2 enzyme (6M03) and EGFR (4HJO) were subjected to 50 ns all-atom molecular dynamics (MD) simulations to examine the ligand-receptor interactions in greater detail. Moreover, the antimicrobial potency of thymopentin against the most prevailing human pathogenic microorganisms was also investigated. The strongest antibacterial activity was observed against “Listeria monocytogenes”, a pathogenic bacterium capable of causing listeriosis, a serious infection that can potentially lead to death. This study revealed the anticancer, anti-Covid 19 and antimicrobial activities of the thymopentin molecule, demonstrating its multifunctional bioactivity. KEY WORDS: Thymopentin, DFT calculations, Vibrational analysis, Molecular docking, Molecular dynamics Bull. Chem. Soc. Ethiop. 2025, 39(10), 2005-2026. DOI: https://dx.doi.org/10.4314/bcse.v39i10.10

Molecular docking is one of the most widely used techniques for simulating molecular interactions between molecules and forecasting the mode of binding and affinities between them. Due to the presence of structure-function relationship, in this study firstly, the molecular structures of the cellulose I(alpha) and I(beta) molecules were optimized and their most stable structures were determined by density functional theory (DFT) using B3LYP method with 6-31G(d,p) basis set. The vibrational wavenumbers of 1-ring, 2-ring, 3-ring, and 4-ring structures of cellulose I(alpha) and I(beta) were calculated using the same level of theory. Reliable vibrational assignments were made based on potential energy distribution (PED %) of the vibrational modes. The energy gap (Eg = ELUMO - EHOMO) of the cellulose Ia and cellulose Ib was found to be 8.286 eV and 7.965 eV, respectively. To identify the molecular interactions between cellulose Ia and Ib ligands and the cellulase enzymes, molecular docking studies were performed. The molecular docking results revealed the strong interaction of the cellulose Ia and Ib with Endoglucanase enzyme (-6.4 and -6.3 kcal/mol, respectively), enzyme β-glucosidase (-5.3 and -5.2 kcal/mol, respectively), and Exoglucanase enzyme (-6.1 and -6.2 kcal/mol, respectively). KEY WORDS: Cellulose I alpha, Cellulose I beta, Density functional theory, Molecular docking Bull. Chem. Soc. Ethiop. 2025, 39(10), 2041-2064. DOI: https://dx.doi.org/10.4314/bcse.v39i10.12

SARS-CoV-2 initiates infection by binding its surface spike glycoprotein to the ACE2 receptor on the human cell surface, facilitating the entry of its genetic material into the human cell. Due to the pivotal role of the spike protein in this infection mechanism, in this study the versatility of the bioactivity of the doxylamine molecule was investigated, and by theoretical molecular modeling studies its potential of blocking the entry of the spike protein into human cells was revealed. In the initial phase of this investigation, conformational analysis of doxylamine was executed employing the PM3 method, yielding six stable conformations. Subsequently, the lowest energy conformation obtained was subjected to optimization at the DFT/B3LYP/6-31++G(d,p) level of theory. Vibrational wavenumbers, highest occupied and lowest unoccupied molecular orbitals, and molecular electrostatic potential for the most stable conformer of doxylamine were computed using the DFT/B3LYP/6-31++G(d,p) level of theory. For docking studies firstly, the optimization by energy minimization feature of the YASARA structure program was employed to both ligand and the ligand-free receptor obtained from the protein databank. Molecular docking simulations were adeptly employed to identify potential compounds with doxylamine anticipated to demonstrate inhibitory activity against the spike protein of SARS-CoV-2. Molecular docking study of doxylamine was conducted with spike receptor-binding domain (RBD) of SARS-CoV-2 (PDB ID: 6M0J). Furthermore, ligand-receptor interactions were scrutinized through a molecular dynamics (MD) simulation lasting 125 ns to verify the stability of doxylamine within the ACE2 binding site.

Bleomycin (BLM) is the first‐line clinical antibiotic used in the treatment of cancer. It inhibits DNA metabolism and is used in conjunction with other anticancer medications to treat various kinds of malignant tumors. This work focuses on examining more fully the bioactivity of BLM as both anticancer and antibacterial agents. Due to the structure–function relationship, the conformational study of the molecule was carried out first, and its potential conformations were identified. Afterwards, using the energy minimization feature of the YASARA structure program, the obtained lowest energy conformation of the molecule and the receptor taken from the protein databank (ligand‐free) were optimized. BLM was subjected to molecular docking tests with two antibiotic‐binding proteins (PDB IDs: 1ewj and 2zw7) to determine its action mechanism as a TN5 transposon inhibitor. Moreover, its binding affinities towards thymidylate kinase (TMK) (PDB ID: 4qgg) Escherichia coli DNA gyrase B (PDB ID: 6f86) were also evaluated to reveal its antibacterial potential. Additionally, ligand‐receptor interactions were assessed via molecular dynamics (MD) process to confirm the stability of BLM docked into antibiotic binding protein (1ewj), TMK (4qgg) and E. coli DNA gyrase B (6f86) within 500 ns (for 1ewj and 6f86) or 200 ns of time (for 4qgg). Molecular mechanics/Poisson‐Boltzmann Surface Area methods (MM/PBSA) were used to compute the binding energies through MD simulations. Dynamics cross correlation matrices (DCCM) analysis and principal component analysis (PCA) on the MD data were performed. Results have cleared the mechanism of action of BLM having anticancer and antibacterial properties.