Journal of Computational Biophysics and Chemistry

Application of the zigzag (24, 0) single-walled carbon nanotube (SWCNT) in delivery of carbamate and imine tautomers of capecitabine is investigated via quantum mechanical geometry optimizations followed by chemical shielding calculations. Torsion angle between ribose and cytosine rings is very close to the experimental value in both tautomers. This suggests that relative orientation of these rings is independent of presence of SWCNT. Their carbon nuclei become closer to the tube’s internal surface by about 1Å, when going from cytosine ring to aliphatic tail. Their cytosine and ribose rings bend so that fluorine atoms and 2${}^{\prime }$-OH group form ion-$\pi$ interaction with the surface. Calculated binding energies aside from observation of these sorts of interactions in these tautomers can propose SWCNT as their potent delivery tool. Most of the obtained conclusions are manifested in the observed trends for calculated chemical shielding values. They make connections among the reported experimental and computational distributions of chemical shielding values inside SWCNTs.

As sensitizers, a series of organic dyes containing phenoxazine is synthesized for use in dye-sensitized solar cells (DSSCs). The dyes were characterized using FT-IR, NMR and UV experiments. Quantum chemical calculations were used to gain insight into the structural, electronic and photophysical properties including its as-synthesized sensitizers, as well as to allocate experimental spectroscopic results. It has been observed that increasing the electron-donor potential and the $\pi$-conjugated bridge of the dyes would increase the photovoltaic performance. The obtained two dyes have substantially higher efficiency of 6.6 and 6.4%, respectively, under the modeled AM1.5G conditions. Efficient electron injection from the excited sensitizer to the conduction band of TiO₂ film occurs due to further delocalizing electrons in the $\pi$-conjugated bridge and donor areas of the dyes. Using cyclic voltammetry, the electrochemical efficiency of BPA and BPCA was evaluated, and reversible oxidation signals were reported.

Parkinson’s disease (PD) is a progressive nervous system disorder and its pathological hallmark is the presence of fibrillar aggregates called Lewy bodies (LB) in substantia nigra. As it is also well established, $\alpha$-synuclein is the major constituent of the LB. Although numerous experimental studies have been conducted on inhibition of $\alpha$-synuclein aggregation, the detailed inhibitory mechanism is not still fully elucidated. In this paper, we first focused on identifying the binding modes of nicotine and dopamine to $\alpha$-synuclein using molecular docking. Then, we performed comparative molecular dynamics (MD) simulations to enlighten the inhibition mechanism of $\alpha$-synuclein for both dopamine and nicotine. MD simulations demonstrate that both nicotine and dopamine stabilize dominant helical structure of $\alpha$-synuclein and so they inhibit their conformational transitions. Moreover, the favorable and unfavorable contribution residues, which play a key role in the inhibition of $\alpha$-synuclein, were determined using MM-PBSA analysis. The findings in this study will shed light on understanding the inhibition mechanism of $\alpha$-synuclein and guide potential drug development studies of degenerative diseases.

Semaglutide is a glucagon-like peptide 1 analog used for the treatment of patients with type 2 diabetes mellitus. With 94% sequence similarity to human GLP-1, semaglutide is a glucagon-like peptide-1 receptor (GLP-1R) agonist, which binds directly to GLP-1R, causing various beneficial downstream effects that reduce blood glucose. Incorporating currently (June 21, 2021) available experimental structural data in PDB of semaglutide and GLP-1R, and with a set of computational structural and biophysical analysis, this short paper for the first time puts forward an experimentally testable hypothesis: semaglutide is able to bind tighter to GLP-1R via a simple Val27-Arg28 exchange in its peptide backbone.

Due to an undecided target and the prescription of chiral-aminoquinolines (chloroquine, primaquine and quinacrine) in the racemic form, the mechanism of action as well as the reason of causing side effects become unclear. Based on computationally evaluated literature data, the things determined theoretically were (i) the target of aminoquinolines during antimalarial activity, (ii) the mechanism of action of chiral-aminoquinolines and (iii) biologically active enantiomers of aminoquinolines. For the presented study, the enantiomeric binding affinities of aminoquinolines with all the targets claimed by other scientists were calculated, and then used in interpretation with the help of many investigations done/observed by others. The results were very interesting based on which, a new and acceptable mechanism of action of chiral-aminoquinolines during malaria curing step, is given for the first time. The current docking study not only resolves the questionable point about a definite target of aminoquinolines but also makes the mechanism of action understandable.

This study spotlights the fundamental insights about the systematic and comparative analysis of four famous hybrid classes of density functional theory (DFT) methods and their efficacy to calculate the linear and nonlinear optical (NLO) polarizabilities. For this study, urea and para-nitroaniline ($p$-NA) molecular geometries are used as prototypes to calculate their linear and NLO properties. For comparative purposes, these molecules are often used as reference organic molecules for determination of NLO response properties and there is a dire need for such a benchmark database to be utilized by the researchers. We report systematically a range of functionals including hybrid (B3LYP, PBE1PBE, BH and HLYP), meta-hybrid (M06, M06-2X, M06-HF, M06-L), long-range corrected (CAM-B3LYP, LC-BLYP, LC-B97D, LC-B97D3) and functional with dispersion correction ($\omega$B97, $\omega$B97X, $\omega$B97XD, HSEH1PBE). These groups are evaluated and their efficiency to calculate linear and NLO properties is graphically compared with each other. Overall, there are less deviations among different functionals for calculating dipole moments of $p$-NA and urea while these deviations enhance as one moves from dipole moment to linear polarizability and nonlinear hyperpolarizabilities. In general, if we look at the trends, the polarizability values of B3LYP, M06-L, CAM-B3LYP and HSEH1PBE are relatively large and can be compared with each other. The dispersion corrected and long-range corrected functionals show more systematic deviations. For instance, among dispersion corrected functionals, the amplitudes of dipole moments, linear polarizability and NLO polarizabilities show an increasing trend as $\omega \mathrm{\text{B}}97<\omega \mathrm{\text{B}}97\mathrm{\text{X}}<\omega \mathrm{\text{B}}97\mathrm{\text{XD}}<\mathrm{\text{HSEH1PBE}}$. It is also important to note that LC-B97D and LC-B97D3 of long-range corrected functional have observed exactly the same values of all the calculated parameters. A good agreement is being observed in static first and second hyperpolarizabilities of urea (B3LYP, M06-L, M06 and HSEH1PBE) and $p$-NA (B3LYP, M06, M06-L, CAM-B3LYP and HSEH1PBE). Thus, we believe that the current investigation will provide the benchmark data of reference NLO molecules at different methods for theoretical community and molecular level insights for experimental community to design better NLO materials for hi-tech NLO applications.

In this paper, three tetrahedral nanocages, composed of six DNA double helix edges with all having the twist number 1, 2 or 3, have been characterized using classical molecular dynamics simulation to measure the specific structural and conformational features produced by only changing the twisting number of each double helix. The simulation result indicates that three tetrahedral cages are relatively stable and are maintained along the entire trajectory. Each double helix is more inclined to behave as a whole in the 2TD and 3TD cages than in the 1TD cage according to the cross-correlation maps for three nanocages, and also their local motions are more easily induced by the conformational variability of the thymidine linkers due to the increased flexibility of each helix. Hence, the double helices become the important factors on the structural stability of total cages with the DNA twisting number, and also give the signification contributions to the sizes of these cages conferring the larger spaces of the 2TD and 3TD cages than the 1TD cage. Our result provides an insight into which roles the double helix edges play in assembling DNA polyhedron, and also contribute to improving the loading capacity of DNA tetrahedron in drug delivery.

In this study, the ability of salvianolic acids A, B, C, F, G and calix[$n$]arenes ($n=4$, 5, 6 and 8) with different upper rims in the inhibition of insulin amyloid fibril formation was studied using molecular docking. The results were analyzed from a molecular point of view. All of the considering ligands interacted with significant residues of insulin, which had a crucial role in the process of insulin fibrillation. The interactions among the ligands and insulin residues could be done through hydrogen bonding and hydrophobic interactions with good binding affinity. So, these ligands could prevent the formation of the insulin fibril. The good consistency of the docking results of $P$-sulfonatocalix[4]arene and $P$-sulfonatocalix[6]arene with the experimental results in the previous literature represented the capacity of the current theoretical method to supplement and interpret experimental findings. Also, in this study, salvianolic acids A, C, F and G were suggested as new inhibitors of the insulin amyloid fibril.