Journal of Computational Biophysics and Chemistry

Human nonreceptor tyrosine kinase (TK) Fyn is implicated in various cellular processes and has been exploited as a sophisticated druggable target of pediatric T-cell lymphoma by blocking its kinase domain with small-molecule inhibitors or disrupting its regulatory SH2 and SH3 domains with peptidic inhibitors. In this study, the proline-heavy 9P1Y-peptide was found as a good binder of Fyn SH3 domain, of which the chemical diversity space was extended by replacing its proline residues with a variety of N-substituted amino acids, since N-substitution can mimic the side-chain location and shape of proline. A systematic single-point N-substituting perturbation profile (SSNPP) for 9P1Y-peptide was created theoretically, from which a systematic combinatorial peptoid library (SCPL) was then generated by introducing favorable N-substituted to different proline residue positions of the peptide. The computational design was further substantiated by fluorescence spectroscopy assays to identify five promising peptoid hits in the SCPL as potential Fyn SH3 binders. In particular, the designed peptoid Ptoid2 exhibited a good affinity to Fyn SH3 domain ($K_d=0.76\mu$M) and a moderate selectivity for Fyn over Lyn (3.8-fold), which are improved substantially from the natural 9P1Y-peptide. Molecular mechanism underlying the N-substituting perturbation effect was also examined in detail.

DFT calculations of ground-state hydrazine and benzohydrazide derivatives were performed by using hybrid functional B3LYP and CAMB3LYP with 6–31G (d, p) as basis set. The electric dipole moment ($\mu )$, polarizability ($\alpha )$ and molecular first hyperpolarizability ($\beta )$ were characterized in these compounds. The HOMO–LUMO energy gaps and the global chemical reactivity descriptors were computed by B3LYP and CAMB3LYP using 6–31G (d,p), while the excitation energies have determined by time dependent DFT (TDDFT). Besides, the stability and charge delocalization were studied by natural bond orbital analysis. Topological analyses such as atom in molecule (AIM), natural bonding orbital (NBO) and molecular electrostatic potential (MEP) have used to compute intermolecular interactions and in particular hydrogen bonds. The obtained first-order hyperpolarizabilities in the range of 1.5 × ${10}^{-30}$ to 30.2 × ${10}^{-30}$ esu revealed that the hydrazine and benzohydrazide derivatives have better NLO properties. The low-energy gap of 3.53 eV generates an intramolecular charge transfer, leading to the enhancement of the NLO activity in these compounds.

Malaria is a serious illness transmitted through the bite of an infected mosquito, which is caused by a type of parasite called plasmodium and can be fatal if left untreated. Thus, newer antimalarials with unique mode of actions are encouraged. Fused pyridines have been vastly reported for numerous pharmacological activities including but not limited to analgesics, antitubercular, antifungal, antibacterial and antiapoptotic agents. In a current study, a series of substituted Imidazo[1,2-a]pyridine-3-carboxamides (IMPCs) (SM-IMP-01-13) along with some hydrazides (DA-01-DA-02) were synthesized and characterized by Fourier-transform infrared spectroscopy (FTIR), ¹H-/${}^{13}$C-NMR (proton/carbon nuclear magnetic resonance), elemental analyses and mass spectra. These synthesized analogies were subjected for in vitro biological activities such as Brine Shrimp lethality (BSL), and assay of $\beta$-hematin formation inhibitions. The BSL assay results suggested that compounds, SM-IMP-09, SM-IMP-05 were found to be less toxic and they also had comparable toxicity as of 5-Flurouracil (control) ((e.g., at 10 $\mu$g/ml: 20% deaths of nauplii). Derivatives SM-IMP-02, and DA-05 inhibited $\beta$-hematin formation: IC${}_{50}$: 1.849 and 0.042 $\mu$M, respectively). Our molecular docking analysis on plasmodial cysteine protease falcipain-2 indicated that compound DA-05 (–9.993 kcal/mol) had highest docking score and it was comparable to standard Chloroquine (–7.673 kcal/mol). The most active molecule, DA-05 was also retained with lower HOMO–LUMO energy gap as 3.36 eV. Further, we have also analyzed MEP, and other global reactivity indexes for all IMPCs using DFT. Finally, our in-silico pharmacokinetic analysis suggested that all compounds were having good% human oral absorption values ($\approx$100%), good Caco-2 cell permeabilities (>1600 nm/s), and non- carcinogenic profiles.

The primary emphasis of this study is on the interactions between heat radiation and viscous dissipation on the MHD flow of Fe₃O₄-ethylene glycol nanofluid along a dwindling sheet with heat absorption/ production and velocity slip is investigated. Consequently, we provide a novel study to develop and comprehend a mathematical model for the non-Newtonian nanofluid flow in a magnetic and porous medium situation. Ethylene glycol (EG) is a commonly used fluid. In order to form the nanofluid, Fe₃O₄ nanoparticles are distributed in EG. The basic governing PDEs are converted into ODEs by appropriate suitable resemblance conversions. Employing the Keller-Box process, the numerical outcome of the governing equations is found. In diagrams and tables, the influence of developing flow aspects on essential flow appearances is elucidated. The results of this research are also contrasted with those found in the previous works. The presence of Eckert number has been shown through computational investigation to increase the temperature curve, whereas the Porosity parameter resulted in a diminution in fluid velocity and an upsurge in fluid temperature. The results demonstrated that the temperature of a fluid improves with increasing thermal radiation and diminishes with raising the heat absorption factor. The suggested concept finds useful applications in the construction of nuclear vessels where the moving plate serves as a rheostat rod, power transmission systems, and molding compression development in nanoscale nanotechnology.

This work reveals how two natural multi-target compounds (Carnosine and Homocarnosine) can prevent the oligomerization of beta-amyloid peptides (A$\beta )$. Properly combining molecular dynamics, docking and electronic structure calculations it was possible to investigate how Carnosine/Homocarnosine strongly interact with the amino acids of the A$\beta$(1-42) peptide responsible for the complexation with metallic ions (metallic hypothesis). This discovery may prevent the formation of harmful protein deposits, thereby preventing the progression of, for example, Alzheimer’s disease (AD). These important results suggest that Carnosine/Homocarnosine can interact with, at least, two of the amino acids responsible for the complexation of the A$\beta$(1-42) peptide with the metallic ion copper(II). These findings open a new perspective on the inhibitory potential of these molecules in the treatment of AD and other neurodegenerative diseases.

Effluents from dyeing companies are a major polluter of the environment and water bodies. An estimated 70 tons of dye are generated globally each year, with more than one-third of this amount lost to the environment. To combat this issue, novel chemical compounds that are more efficient than existing ones are proposed. The soft synthetic approach was used to create [Ni(II)(Tpy)₂] MOF by reacting nickel nitrate with terpyridine (Tpy). The melting point of the MOF was determined, as well as the EA, HSM, TGA, PXRD, and X-ray crystallographic studies. The MOF results support the synthesis and coordination of the nickel (II) ion with the two Tpy molecules. In application, [Ni(II)(Tpy)₂] MOF was utilized to study the adsorption of Congo red. After 30 min of adsorption time, 1 g of [Ni(II)(Tpy)₂] MOF adsorbed a high amount of Congo red (138.26 mg) at $25^{\circ }$C and a pH of 2. When compared to other isotherms, the Langmuir isotherm provided the best fit. Adsorption kinetics demonstrating electrostatic interaction between MOF and Congo red might be interpreted using the pseudo-second-order model.

Density functional theory, Monte Carlo, and molecular dynamics simulations of the [Ni(II)(Tpy)₂] MOF over Congo red dye were computed. Density functional theory calculations provide insights into the reactivity of the novel [Ni(II)(Tpy)₂] MOF by furnishing chemical reactivity parameters that explain the interactions and adsorption processes between the [Ni(II)(Tpy)₂] MOF and Congo red. The quantum mechanical calculations provide data for an insightful understanding of the reactivity of the MOF and its high adsorption on the Congo red surface. Low band gaps (1.40 and 1.43 eV in the gas phase and water, respectively) obtained for the [Ni(II)(Tpy)₂] MOF suggest that this will make an extrinsic semiconductor with high electrical conductivity. Thus, it would readily interact with and be adsorbed on the Congo red.

Irritable Bowel Syndrome (IBS) is a gastrointestinal disorder that affects 7-21% of the world’s population. People suffering from this illness can have a significant change in their quality of life and their productivity at work. Medicinal plants and their derived products have long been explored and used for their medicinal qualities throughout the world to cure numerous ailments, including gastrointestinal problems. The main aim of this study was to predict highly efficacies therapeutic molecules from the medicinal plant, Aegle marmelos to bind potential target against IBS and gastrointestinal protection, using in silico molecular modeling tools. A total of 16 phytocompounds were identified through the IMPPAT database from A. marmelos, and their structures were drawn by Chemsketch software. All the phytocompounds were docked against the chosen potential target protein, Motilin receptor (MLNR). The selected phytocompounds showed better binding affinities (–5 to –8.4 kcal × ${\text{mol}}^{-1}$) against the target. Top-scored phytocompounds from A. marmelos, Aegeline (–8.4 kcal × ${\text{mol}}^{-1}$), Alloimperatorin methyl (–8.2 kcal × ${\text{mol}}^{-1}$), and Imperatorin (–8.2 kcal × ${\text{mol}}^{-1}$) were selected for further evaluation and compared to the standard drug R093877 (–6.7 kcal × ${\text{mol}}^{-1}$). Drug-likeness, ADME & T and other physicochemical properties of selected top scored phytocompounds were assessed to confirm their druggability. The molecular dynamics simulation studies of selected top scored phytocompounds showed stable binding affinities with the MLNR protein on entire period. Based on these findings, the top three scored phytocompounds might be used as potent and safe molecules against the MLNR protein and could potentially be used in the treatment of IBS.

This study is motivated by the vital role of dissipating thermal energy in the physiological system where energy depletion can lead to severe health complications. These complications encompass a range of issues, including sudden death, anemia, hypothermia, blood pressure fluctuations and the necessity for cardiac surgery. Biomedical engineers and clinicians have recognized the significance of analyzing entropy generation to quantify energy loss in biological systems. Furthermore, this study acknowledges the importance of understanding the thermodynamic state of entropy generation, particularly in evaluating cancer cells during chemotherapy treatment and enhancing heat transfer in tissues. The primary objective of this study is to evaluate the heat transfer characteristics of a magnetohydrodynamic (MHD) tangent hyperbolic hybrid nanofluid near a heat source and thermal radiation as it flows over a porous plate. The research methodology utilizes the MATLAB program bvp4c for solving the momentum and temperature equations. These equations are subsequently transformed into ordinary differential equations using the appropriate self-similarity variables. An elevation in the heat source parameter leads to heightened internal energy of liquid particles, resulting in an increase in temperature. Additionally, the magnetic field parameter is directly proportional to the entropy generation; as it increases, so does the entropy generation. Moreover, nanoparticles, owing to their high surface area-to-volume ratio, have the capacity to hinder heat transport within the fluid. The specific application of this study lies in the field of biomedical engineering and clinical practices. The findings can contribute to developing advanced heat-transfer techniques for medical applications, such as improving chemotherapy treatments for cancer cells and enhancing tissue heat-transfer efficiency. Moreover, using silver and copper nanoparticles as heat-transfer agents could hold promise in treating blood-related health conditions and facilitating the healing of injured tissue.