Narrow Results

We have investigated the decomposition of C₆₀ molecules with low and high coverages on Si(100)(2×1) surface at elevated temperatures. We also investigated the decomposition of an isolated C₆₀ molecule. We employed molecular-dynamics simulation using a model potential. It has been found that C₆₀ decomposes on Si(100) surface after 1000 K in the case of low coverage (0.11), however in high coverage case (0.67), C₆₀ molecules decompose after 900 K. On the other hand, isolated C₆₀ molecule decomposes after 7500 K, interestingly it shows a phase change from 3D to 2D at higher temperatures.

Chignolin is an artificially designed ten-residue (GYDPETGTWG) folded peptide, which is the smallest protein and provides a good template for protein folding. In this work, we completed four explicit water molecular dynamics simulations of Chignolin folding using GROMOS and OPLS-AA force fields from extended initial states without any experiment informations. The four-folding free energy landscapes of the peptide has been drawn. The folded state of Chignolin has been successfully predicated based on the free energy landscapes. The four independent simulations gave similar results. (i) The four free energy landscapes have common characters. They are fairly smooth, barrierless, funnel-like and downhill without intermediate state, which consists with the experiment. (ii) The different extended initial structures converge at similar folded structures with the lowest free energy under GROMOS and OPLS-AA force fields. In the GROMOS force field, the backbone RMSD of the folded structures from the NMR native structure of Chignolin is only 0.114 nm, which is a stable structure in this force field. In the OPLS-AA force field, the similar results have been obtained. In addition, the smallest RMSD structure is in better agreement with the NMR native structure but unlikely stable in the force field.

This work performed molecular dynamic simulations to study the 2D profile and 3D surface topography in the nanometric cutting process. The least square mean method was used to model the evaluation criteria for the surface roughness at the nanometric scale. The result showed that the cutting speed was the most important factor influencing the spacing between the peaks, the sharpness of the peaks, and the randomness of the profile. The plastic deformation degree of the machined surface at the nanometric scale was significantly influenced by the cutting speed and depth of cut. The 2D and 3D surface roughness parameters exhibited a similar variation tendency, and the parameters Ra and Rq tended to increase gradually with an increase in the cutting speed and a decrease in the depth of cut. Finally, it is concluded that at the nanometric scale, the 3D surface roughness parameters could more accurately reflect the real surface characteristics than the 2D parameters.

The study of the corrosion inhibition of mild steel in acid medium 1 M HCl by the Schiff base compounds named {4,4′-Bis(pyrrole-2-carboxaldehyde) diphenyl diimino sulfide (L1) and 4,4′-Bis(thiophene-2-carboxaldehyde) diphenyl diimino sulfide (L2)} was carried out using various techniques: weight loss measurements, polarization curves, electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM), Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). The influence of the concentration, immersion time and temperature was examined and the mode of adsorption of these inhibitors on the surface of the metal was highlighted by assigning the appropriate isotherm. The experimental results indicate that these compounds are effective corrosion inhibitors and the inhibitory competence rises with increasing inhibitor concentration. The adsorption of these compounds on the mild steel surface obeys the isotherm of Langmuir. The correlation between the molecular structures and the inhibitory properties of the compounds studied was performed using the Density Functional Theory (DFT) method. Furthermore, molecular dynamics (MD) simulation has been taken into account. The results indicate that the adsorption energy of L1 was less than L2, which is in accordance with the experimentally determined inhibition effect.

Magnetic nanoparticles (MNPs) can be used in a wide variety of biomedical applications like contrast agents for magnetic resonance imaging, magnetic labeling, controlled drug release, hyperthermia, and in cell isolation. Most of these applications need distinct and controllable interactions between the MNPs and living cells and can be made possible by a proper functionalization technique. This paper describes a computational approach for the identification of magnetic nanoparticles for the development, design, and demonstration of a novel, incorporated system for selective and rapid removal of biological, chemical, and radioactive biohazards from human body.

The attraction between an external magnetic field and the MNPs facilitate separation of a wide variety of biological materials. This principle can be used for the isolation and aggregation of wandering cancer cells from the blood or the bone marrow to make a proper and early diagnosis of leukemia. Similarly, toxins, kidney stones, and other unwanted particles in the human body can be easily diagnosed and removed by the same technique.

Nanoparticle-sized iron oxides have been studied in this work by computational modeling and molecular dynamic (MD) simulation techniques. Structural, thermodynamic, and magnetic properties have been formulated. In this work, nanoparticles of size varying from 0.5 to 2.5 nm have been analyzed. Cell isolation ability of the nanoparticles has been compared based on the computational results.

MNPs are biologically activated and permitted to bind with the targeted cells through various pathways, thereby allowing certain cellular compartments to be specifically addressed. Once the cells are identified, the preferred cellular compartments can be magnetically isolated and removed with the help of an external magnetic field. Out of the iron oxides analyzed in this work, 1.1 nm Fe₃O₄ is found to be most interacting with leukemia protein. Hence, leukemia cells can be effectively targeted, separated, and removed using Fe₃O₄ of the suggested dimension.

Carbon nanotubes have been identified as the promising agents in reinforcing composite materials to achieve desired mechanical properties. In this study, three different types of single wall carbon nanotubes (SWCNTs) are subjected to molecular dynamics simulation to investigate their mechanical properties taking different interatomic potential functions. With unmodified Brenner's 2nd generation potential, a brittle fracture for all the SWCNTs is observed. But in tight-binding approach, the chiral and armchair SWCNTs exhibit somewhat extended plastic flow region before failure. With unmodified Brenner's potential, high tensile strength and ductility are observed for the armchair and chiral tubes. Y value of these two tubes is less than 1 TPa but more than 1 TPa for a zigzag tube. Much decrease of tensile strength and strain are noticed when we apply smoothing of the Brenner's potential at cut-off region. Failure stresses are dropped to much lower values for the three tubes. Ductility of the armchair and chiral tubes are also affected considerably by the choice of potential. Applying smoothing in the cut-off region to conserve the energy, the results show better agreement with the experimental findings.

Protein tyrosine phosphatase 1B (PTP1B) is one of the important regulators of signal transduction pathways. The present study aims to investigate the effect of Arg 221 on the active site of PTP1B. Six mutants were carried out using Schrödinger Suite 2007 and molecular dynamics simulation was performed by using the Tinker package. Results show that point mutations at position 221 have great influence on shape of active site, backbone movement of active site, and interaction between substrate and PTP1B. R221H and R221K lead to increased total interaction energies. R221G, R221F and R221T cause increase in total interaction energies, but decrease in interaction energies between pTyr 4 and P loop (catalytic residues). R221E results in both decreased total interaction energies and interaction energies between pTyr 4 and P loop. This indicates that Arg 221 mutated to basic residues can lead to enhanced binding affinity between substrate and protein; when mutated to acidic residues it will decrease binding affinity and catalytic activity; other kinds of mutations result in increased binding affinity but decreased catalytic activity.

Molecular dynamics (MD) method was used to simulate the interaction between water-soluble polymers, such as polyacrylic acid (PAA), polymethylacrylic acid (PMAA), acrylic acid-methylacrylate copolymer (AA-MAE), acrylic acid-hydroxypropyl acrylate copolymer (AA-HPA), hydrolyzed polymaleic anhydride (HPMA), acrylic acid-maleic acid copolymer (AA-MA), and hydroxyapatite crystal. The sequence of binding energies of polymers binding with the (100) crystal surface of hydroxyapatite was as follows: AA-HPA > AA-MA > HPMA > PAA > AA-MAE > PMAA. After analyzing various energy components and pair correlation functions of all systems, it could be concluded that binding energies were mainly determined by Coulomb interaction. Polymers deformed during their combining with the hydroxyapatite crystal, but all the deformation energies were far less than respective nonbond energies. The dynamics behavior of carboxyls located at different positions of the polymer chains manifested different features during the processes of MD runs. Carboxyls at the ends of the polymer chains oscillated more acutely than those in the middle of the chains; therefore, the latter ones inhibited scale crystal growth more effectively than the former ones because they combined with hydroxyapatite crystal more firmly.

We studied the interfacial features of 1-butene/water and extraction process of 2-butanol by molecular dynamics (MD) simulations. The infinite dilute diffusion coefficients of 1-butene in water is larger than that of 2-butanol, and one important reason is that 2-butanol molecules can form hydrogen bonds with water molecules. 1-butene is more soluble in water under supercritical condition than that under subcritical condition. 1-butene under supercritical condition can extract more 2-butanol from aqueous solution than that under other conditions. A process of producing 2-butanol by the direct hydration of 1-butene is more competive when it operates under the supercritical conditions of 1-butene which due to a higher solubility of 1-butene in water, a larger diffusion coefficient of 1-butene and a lower 2-butanol concentration in water.

Diffusion in liquid SiO₂ nanoparticle with the diameter of 4 nm has been studied in a spherical model containing 2214 atoms via Molecular Dynamics simulation (MD). Diffusion constant of atomic species has been calculated over temperatures ranged from 2100 K to 7000 K and compared with those observed for the bulk. We found that temperature dependence of diffusion constant of atomic species in nanoparticle shows an Arrhenius law at temperatures above 2100 K and at T > 4200 K, it deviates from an Arrhenius law. However, unlike those observed in the bulk at T > 4200 K, it does not show a power law, D ~ (T - T_c)^γ. Moreover, at relatively low temperatures, diffusion constant in nanoparticle is higher than that in the bulk indicating the surface dynamics effects.

Nano Fe₄N powder has been successfully prepared by the combination between high pressure combined method of reduction and nitriding and molecular dynamics (MD) simulation. The phase, composition, morphology, and magnetic properties have been preliminarily characterized by XRD, TEM, and VSM to investigate the influence of temperature, time, ammonia hydrogen ratio, and pressure during reaction process on the preparation. The results indicate that the preferable nano Fe₄N powder of the average size around 35nm could be obtained nitriding at 0.4MPa and 673K for 2.5hours with the ammonia hydrogen ratio being 3:1. The results of magnetic detection show that the nano Fe₄N produced here is a fairly desirable soft magnetic material with Ms$=$169.70emu/g. This process could reduce the reaction temperature and shorten the reaction time, which is of important significance to the industrial production of nano Fe₄N powder.

Fungal infection of invasive nature is an alarming threat globally and a leading cause of human morbidity and mortality as they are opportunistic in nature. Rising resistance to current clinically approved marketed products for fungal infections is a major concern for humans. Dihydrofolate Reductase (DHFRase) is an essential enzyme in folate metabolic pathway responsible for DNA synthesis and is ubiquitous to all organisms, and also acts as a key target for developing antifungal drugs. In this study, potential mutant DHFRase inhibitors were screened with the help of hierarchical mode of docking of virtual library of antifungal compounds and molecular dynamic (MD) simulation. The identification of best hits was done by using the docking, binding energy prediction and further, which was supported by their predicted pharmacokinetics. MD simulation of the human DHFRase enzyme with the reference lead compound i.e. PY957 and most promising hit found i.e. ChemDiv-C390-0455 and to validate the stability of enzyme-ligand complex in best 07 retrieved hit as a potential mutant DHFRase inhibitor. The key residues Glh30, Phe34, Phe64, Phe31 of the binding pocket acknowledged as essential were found to be matching with the key interactions of the selected hit. Computed root mean square deviation (RMSD) and root mean square fluctuation (RMSF) in MD simulation of complex of DHFRase enzyme with PY957 and ChemDiv-C390-0455 were read less than 2.25Å during 100 nanoseconds simulation for both complex.

Upregulation of MAPK pathway receptors has been majorly reported for the accumulation of tumor cells in non-small cell lung cancer (NSCLC) patients. Several scientific endeavors were committed to developing checkpoint inhibitors for MAPK intermediates. However, poor toxicity profiling and over-expression of other kinases diminish the treatment outcomes. Recently, dual-action drugs are developed to overcome the ineptness and drug resistance that typically occur when the usage of individual checkpoint inhibitors. Therefore, we screened 1574 natural compounds from the NPACT database using high-end computational tools against these attractive kinase targets (RAF and MEK). Initially, Glide docking and prime-MM/GBSA analysis yielded a total of seven hit compounds that showed better binding potency on both targets. The van der Waals interaction energy highly favors the binding of the compound with respective target receptors. Later, we used dynamics ensembles to examine the essential and stable interactions in the complex structures through 16 different MD simulations (50ns) cumulatively in both RAF and MEK systems. These extensive MD analyses resulted in two lead compounds such as NPACT00282 and NPACT01075 having the potential to make a stable complex with RAF and MEK receptors. Notably, the interaction of compounds with CYS532 and TYR125 in RAF and MEK, respectively, might play a crucial role in the compound’s binding process. Furthermore, these lead compounds exhibited good pharmacokinetic/dynamic characteristics. Collectively, we believe that these lead compounds are able to provide better therapeutic options and thus overcome the shortcomings in lung cancer treatment.

Amyloid $\beta$ (A$\beta$) peptide monomers polymerize to form insoluble amyloid fibril aggregates and accumulate as senile plaques which eventually leads to cognitive impairment. Modulating abnormal amyloid aggregation can be considered a therapeutic target for Alzheimer’s disease. Recent studies support that Curcumin interferes with larger protein aggregate formation by destabilizing the salt bridge (Asp 23-Lys 28) of A$\beta$ protein. The chemical library of curcumin derivative with pyrazole, isoxazole, and isothiazole showed considerable binding affinity comparable to that of curcumin. In silico docking studies of the library of the compound, revealed strong binding affinity with A$\beta$ protein and $\beta$-secretase enzyme (BACE1). De novo ligand design coupled with manual pharmacophore mapping of our best-fitting lead revealed another ligand having a potential binding affinity with both A$\beta$ protein and BACE-1. Both the compounds passed Lipinski’s Rule of Five, in silico toxicity testing by admetSAR, and pharmacophore overlaps with Verubecestat, a compound under clinical trial against Alzheimer’s disease. MD dynamic simulation study revealed the stability of protein after it binds to our ligand. Secondary structure determination was also done to observe the changes in $\alpha$ and $\beta$ sheets of the protein with and without ligand binding. Ligand-based drug design was also carried out via pharmacophore mapping and searching the molecules via zinc database.

The aim of the study is to design and synthesize thiazolidinone derivatives having therapeutic potential using PABA as a core component. The characterization of thiazolidinones MS1–MS6 was carried out using different spectroscopic techniques before being subjected to DFT studies to calculate various parameters such as HOMO/LUMO energy gaps and global chemical properties. Thiazolidinones MS1–MS6 were screened to evaluate their in vitro enzyme inhibition potential. In addition to experimental work, theoretical approaches were used as supporting components to design the enzyme inhibitors. In-silico ADMET and docking studies were performed to check the therapeutic properties of thiazolidinone derivatives. The enzyme inhibition potential predicted that MS1–MS6 have potential to inhibit AChE and BChE. The highest activity was depicted by MS4 with a percentage inhibition of 81.7 ± 1.1% against AChE. The molecular dynamic simulation was run for MS4 showing a similar activity on enzyme compared to the standard inhibitor. Both experimental and theoretical assessments suggested the therapeutic importance of the thiazolidinone derivatives MS1–MS6. In-depth studies are ongoing to complete therapeutic probing in terms of toxicity and chemical uses.

The activation of the Neuraminidase 3 (NEU3) enzyme has been associated with the hyperphosphoryla-tion of Epidermal Growth Factor Receptor (EGFR) in Nonsmall Cell Lung Carcinoma (NSCLC). Existing EGFR inhibitors (such as gefitinib, erlotinib, lapatinib, icotinib, afatinib and osimertinib) reduce the hyperactivation of downstream signaling pathways (Akt, Mapk, Jak-Stat, Plc) but fail to completely abolish EGFR hyperphosphorylation. Therefore, co-targeting NEU3 and EGFR presents a greater potential to be used as a combinatorial therapy for NSCLC. This study employs structure guided approaches to elucidate the binding hypothesis of NEU3 and EGFR inhibitors. Toward this, important 3D features associated with high inhibitory potency of NEU3, and EGFR modulators were identified through SAR. The triazole substitution in acetamide dihydropyran carboxylic acid derivatives is mainly responsible for improved inhibitory potency against NEU3. Therefore, the hydrophobic ($\varphi$-H) interaction with the benzene ring and hydrogen bonding with the hydroxyl group of triazole are critical for designing new NEU3 modulators. Molecular Dynamics (MD) simulation studies demonstrate the stability of hydrogen bonding interactions of highly active NEU3 inhibitors with Pro66, Gly199 and Glu410 residues. Similarly, pyrimidine ring of EGFR inhibitors forms stable hydrogen bonds with Lys721 and Asp831 residues, contributing to their inhibitory potency. Our findings suggest that incorporating these identified 3D features associated with triazole and pyrimidine substitutions into a suitable scaffold could be a valuable strategy for developing a new generation of NEU3 and EGFR modulators. This approach offers a potential multi-targeted therapy for NSCLC patients.

F_O is a membrane-embedded part of ATP synthase, transforming proton current running within this molecule into a rotational motion taking place between two subunits, c-subunit and a-subunit. How the proton current could be transformed into the rotational motion remains unclear. In this paper, by means of molecular dynamics simulation, we studied basic properties of the rotational motion. In equilibrium, the c-ring, which consists of 10-12 c-subunits and interacts with the a-subunit, showed stepwise rotational motion. The rotational motions resulted in a free rotational diffusion in a longer period. The diffusion constant calculated as a function of temperature showed a glass-transition-like behavior: at the lower temperatures, diffusional motion was significantly suppressed, deviating from the Einstein's relation. Under a non-equilibrium condition where different heat baths with different temperatures are applied, respectively, to the c-ring and the a-subunit, we found that directionality arises in the rotational diffusion. We finally point out how the structural flexibility (i.e., softness) of protein molecules pertains to our results.