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Under hyperglycemic conditions, proteins undergo structural modifications non-enzymatically, resulting in the formation of advanced glycation end products (AGEs). These AGEs contribute to the production of free radicals, which in turn exacerbate the development of diabetes and its complications. Therefore, inhibiting glycation is anticipated to play a crucial role in managing diabetes. Here, we have examined the effect of 2-hydroxy-1,4-naphthoquinone (NQ) and silibinin on ribose-mediated glycation of HSA. Presence of NQ and silibinin inhibited the fluorescent AGEs formation by 79.18% and 84.10%, respectively. Moreover, the secondary structural loss caused by glycation was restored by NQ and silibinin treatment. Both the compounds showed higher affinity toward native HSA compared to glycated HSA as evident from their binding constants. Molecular docking showed a direct interaction of tested compounds with glycation prone amino acids arginine and lysine residues of HSA. Molecular simulation studies confirmed the NQ or silibinin formed stable complex with HSA. Both the ligands formed hydrogen bonds throughout the trajectory. MM-PBSA calculation showed the overall binding energies for silibinin and NQ with HSA were – 16.863 kcal/mol and – 9.977 kcal/mol, respectively. The findings show the antiglycation potential of NQ and silibinin against ribose mediated glycation of HSA along with mode of action.

The WNT10A gene, which codes for the WNT Family Member 10A (WNT-10a) protein and regulates WNT signaling pathways, has been linked to dental anomaly. WNT-10a protein binds with Frizzled (FZD (FZD1, FZD5 and FZD10) receptors and is involved in tooth development. Mutations in the WNT10A gene cause Oligodontia, tooth agenesis, microdontia and root maldevelopment by impairing WNT signaling. In addition, mutations in the WNT10A gene affect its structure and functional behavior of interaction with FZD receptors. However, the structural changes and interaction behavior of WNT-10 protein upon mutation at the molecular level are still unclear. Hence, in this study, the structural consequences of WNT-10a mutations at the atomic level were elucidated using a molecular simulation approach. Furthermore, docking simulations and MM-GBSA approaches were applied to investigate the interaction pattern of FZD proteins upon mutation in the WNT-10a protein. This study demonstrates that when the WNT-10a protein loses stability, the G213S mutant becomes more flexible, whereas R293C and T357I mutants become more rigid than the wild-type protein. This structural loss affects the interaction between WNT-10a and FZD1, FZD5 and FZD10 receptors which dysregulate the WNT signaling pathway in tooth development. Understanding this mechanism at a molecular level will be beneficial for treating dental anomalies.

The degree of polymerization (DP) has been regarded as an important symbol of mechanical strength, reflecting the aging condition of transformer insulation paper. In this article, a new concept called fracture degree is proposed on the basis of DP. First, nine cellulose I_β crystal models with different fracture degrees were built. Then relevant mechanical parameters and hydrogen bond numbers were calculated by molecular dynamics (MD) simulation. Results showed that during the aging process of insulation paper with fracture of cellulose chain, the elastic constant C₃₃ produces appreciable impact on the Young's modulus (E). With the decrease of DP and increase of fracture degree, the Young's modulus step decreases. To the 50% and 100% fracture degree models respectively, the relationship between their different degrees of polymerization and Young's modulus is subjected to similar exponential distributions. With the increase of the fracture degree, the average hydrogen bond number drops, and the change rules apply to the Young's modulus. Since hydrogen bond is the main factor of mechanical strength, it can be inferred that the fracture degree influences mechanical strength seriously.

Hydrogen sulfide (H₂S) in acid gas reservoirs is an important source of sulfur deposition in rock reservoirs. Studying the adsorption behavior of H₂S in calcite slit-like pore is of great significance for predicting the amount of sulfur in natural gas. In this paper, the grand canonical Monte Carlo (GCMC) method is used to investigate the adsorption of H₂S in calcite with slit-like pore. Moreover, the effects of different pressures, temperatures and pore sizes on the adsorption characteristics are discussed. The results showed that the adsorption of H₂S goes up with the increasing of the pressure and gradually reaches a saturation level. And the adsorption of H₂S decreases with the increasing of the temperature. The excess adsorption of H₂S first increases and then decreases with the increasing of the pressure. The effect of the size on the excess adsorption capacity changes with the pressure. Meanwhile, the peak of the adsorbate near the surface of the adsorbent shows a nonmonotonic trend with the pressure.

The addition of porous nanomaterials is promising to enhance the thermal energy property of the organic working fluid. In this paper, molecular dynamics (MD) and grand canonical Monte Carlo simulations are employed to investigate the adsorption and energy storage properties of R32, R134a and R1234yf in MOF-5 and MOF-177. The results showed that the working fluid with small molecular size is easier to absorb and desorb in MOF structure. Besides, the MOF with larger specific surface area and pore size can absorb more organic working fluids, which can result in the larger enhancement of energy storage.

In concentration gradient (CG) nano-polycrystalline Ni-Co alloy, the deformation mechanism of each region is different with the increase of Co content. It is found that in the Co-free region, grain boundary diffusion and dislocation slip mechanisms are dominant, while in other regions, there is a synergistic effect of solid solution strengthening. Moreover, the formation of new small grains by the migration of GB atoms will assist in the deformation of large grains, and the alloy exhibits gentle and stable stress–strain curve pattern. Meantime, although the dislocation density of each region is different, the dislocation density still changes stably before and after shearing. Compared with the uniform structure, the flow stress fluctuation is small when the CG structure is plastically deformed, which proves that this kind of structure is more stable. Moreover, it is found that at different temperatures, the CG alloy also shows stable dislocation density and coordination of various mechanisms, which ensures the strength stability. It is revealed that the CG structure has important properties that make the material strength more stable. This work demonstrates the excellent properties of CG alloy and has positive guiding significance for the development of low-cost, high-performance materials in terms of theoretical and practical applications.

Polyhedron structures changes in Lennard–Jones (LJ) liquid argon containing 108 atoms are investigated by means of molecular dynamics (MD) simulations during the glass transition. The local bond orientational parameter and the bond angle distribution are calculated. In particular, a new parameter is introduced to simultaneously quantify the changes of all the major polyhedral structures: tetrahedron, hexahedron, octahedron, dodecahedron, and icosahedron. The results show that icosahedral order, hexahedral order and octahedral order increase with decreasing temperature, while tetrahedral order and dodecahedral order decrease. This indicates that the glass transition is a solidification process with complex microstructure changes.

Generally, with the help of adding solid materials, the thermophysical behaviors of refrigerant can be modified. In this work, four kinds of organic refrigerants (i.e. ethane R170, 1-fluoroethane R161, 1,1-difluoroethane R152a, and 1,1,1-trifluoroethane R143a) mixed with metal–organic framework UIO-67 nanoparticles are selected as the objects, their thermodynamic energy, adsorption, desorption heat, and energy storage properties are investigated by means of molecular simulations and thermodynamic calculations. The simulation method and calculation details are elaborated. The results illustrate that the relationship between the change of thermodynamic energy and the temperature is linear, and the adsorption of refrigerants in UIO-67 can be reinforced owing to the fluorine atom in the refrigerants. However, R170, the fluorine-free refrigerant, has greater enthalpy variation of desorption than the other three refrigerants containing fluorine atom under some pressures. The thermal energy storage capacity of the refrigerant/UIO-67 mixture is greater than that of the pure refrigerant at low pressure. Meantime, as the refrigerant undergoes phase transition, the weakened improvement of the energy storage property of the refrigerant/UIO-67 mixture is found in some cases. This work can not only enrich the content of researches about metal–organic heat carrier nanofluids (MOHCs), but also provide guidance for the performance improvement and practical application of organic refrigerants.

As an environmental vegetable insulation oil, camellia oil will be decomposed into dissolvable gases in the presence of electric field. In this work, the characteristic gases of camellia oil were measured by experiments with partial discharge and breakdown discharge, and the decomposition process of triglyceride, which is the main component of camellia oil, was investigated using molecular simulations (MSs). The experimental results demonstrate that H₂ is the main characteristic gas caused by the partial discharge while C₂H₂ is the main decomposition products for the breakdown discharge. According to the MS results, the C–O bond connected to the center carbon in glycerol breaks initially when the electric field strength is lower, and the C–(O–C) bond in the triglyceride molecule breaks while the electric field strength exceeded critical value with increase of voltage. The decomposition gas generates gradually through decomposition and recombination of radicals, H₂ and CH₄ are the main gas products generated by triglyceride with low electric field strength, while the C₂H₂ increases gradually and becomes the main gas product with the energy of the system accumulated.

Neocarzinostatin (NCS) is an antitumor chromophore carrier protein with many applications in clinical use such as drug delivery system; however, so far its chromophore-releasing mechanism remains unclear. In this contribution the process and pathway of the chromophore releasing from holoprotein are revealed by conventional molecular dynamics simulations and essential dynamics (ED) sampling method. The results are consistent with the model for ligand release proposed in [D. H. Chin et al., J Biol Chem281:16025, 2006]. The further analysis suggests that the conformational changes of loop 99–104 and motions of side-chain of residue Phe78 are important factors for chromophore release; the opening state of loop 99–104 is a precondition for the release of ligand.

The understanding of biological ligand–receptor binding processes is relevant for a variety of research topics and assists the rational design of novel drug molecules. Computer simulation can help to advance this understanding, but, due to the high dimensionality of according systems, suffers from the severe computational cost. Based on the framework provided by conformation dynamics and transition state theory, a novel heuristic approach of simulating ligand–receptor binding processes is introduced, which is not dependent on calculating lengthy molecular dynamics trajectories. First, the relevant portion of conformational space is partitioned with meshless methods. Then, each region is sampled separately, using hybrid Monte Carlo. Finally, the dynamical binding process is reconstructed from the static overlaps between the partial densities obtained in the sampling step. The method characterizes the metastable steps of the binding process and can yield the corresponding transition probabilities.

Though subject to intensive studies, the formation mechanism of buckminsterfullerene C₆₀ and related higher fullerenes has long evaded discovery. To elucidate their atomistic self-assembly mechanism, we have performed high-temperature quantum chemical molecular dynamics simulations on carbon vapor model systems initially consisting of C₂ molecules. Our simulations reveal a coherent mechanism how highly ordered fullerene cages naturally self-assemble under nonequilibrium conditions, following a series of irreversible processes from the polymerization of C₂ molecules to vibrationally excited giant fullerenes, which then shrink by C₂ evaporation down to the smallest spherical, isolated pentagon rule obeying species C₇₀ and C₆₀ as the smallest and kinetically most stable species of the shrinking process. We show that the potential energy surface associated with giant fullerene cage growth, measured by an average cluster curvature, is downhill all the way, and in agreement with high-level energetics from density functional theory. This fullerene formation mechanism is a good example of dynamic self-assembly leading to dissipative structures far from thermodynamic equilibrium, and the "shrinking hot giant" road provides a natural explanation for the observed cage size distributions in a random optimization process consistent with several important experimental observations.

The study on the evolution of natural ferroan brucite (MgFe(OH)${}_2)$ was beneficial to discovering the function of brucite in the geologic cycle and directing the reasonable utilization of brucite resources. In this study, natural MgFe(OH)₂ was characterized in detail and Rietveld refinement was employed to determine the precise content and existing environment of Fe${}^{2+}$. The reaction products of MgFe(OH)₂ under various atmospheric conditions, including CO₂, O₂ and a mixed atmosphere of CO₂ and O₂ were innovatively investigated to gain insights into the evolution process and the crucial role played by Fe${}^{2+}$. Accordingly, the evolution mechanism of MgFe(OH)₂ under different atmospheres was afforded based on the characterization and molecular simulations like electron transfer and binding energy. Fe${}^{2+}$ in MgFe(OH)₂ layers could be oxidized by O₂ easily and give positive layers, CO${}_3^{2-}$ produced by CO₂ dissolving in water simultaneously was attracted to finally produce CO${}_3^{2-}$ intercalated MgFe- layered double hydroxides (MgFe-CO${}_3^{2-}$-LDHs) which could be used as adsorbents, catalysts and so on. This process was supported by thermodynamics and also the dominant evolution route due to the dynamic reason. The existence of Fe${}^{2+}$ in MgFe(OH)₂ resulted in the diversity of the evolution products. This work highlighted the composition and structure of evolution products of natural MgFe(OH)₂ under different environment as well as its possible application field.

We present a combined computational/experimental study of fluorescent Au nanocluster complexes synthesized using small biological molecules. Using density-functional theory, we calculated the binding energy, HOMO–LUMO gap, charge transfer, and bond length of the ligand–Au nanocluster systems. These calculations suggest the formation of ligand–Au nanocluster complexes. We further simulated the HOMO/LUMO states and the absorption spectra of the complexes. The HOMO and LUMO states of the complexes were confined within the Au nanoclusters, suggesting little ligand intrinsic fluorescence. The simulated absorption spectra agreed reasonably well with the experimental data. The simulation results of different systems demonstrate the strong ligand effects on the fluorescent emissions of ligand–Au nanocluster complexes. Our studies provide valuable information for the rational design of next-generation fluorescent tags.

Metal ions are ubiquitous in complex with proteins and play key roles in protein structure and function. The ion-protein interactions are electrostatic delicate in nature, however, the description of electrostatic interactions could be problematic in conventional additive fixed-charge force fields. With empowered computational sources going beyond the common approximations, many efforts have been done to take account in more elaborate electrostatic description in molecular modeling using more sophisticated physical models and dilated algorithms/implementations. Here we review rencent progress in advanced polarizable models and new impletment approaches towards accurate electrostatics and highlight some successful application cases in ion-protein interaction systems in recent years.

The Hsp90 family has been extensively studied as a promising target against cancer and neurodegenerative diseases due to its crucial role in protein maturation and transport. However, the toxic and side effects such as cardiotoxicity and ocular toxicity caused by the pan-inhibition of Hsp90 cannot be ignored. The development of highly selective inhibitors toward Hsp90$\alpha$ over Grp94 has been proved to be a feasible approach to avoid these toxic and side effects. Therefore, to explore the different binding modes of inhibitors against Hsp90$\alpha$ and Grp94, hybrid computational methods were used to demonstrate the interaction mechanism between selective inhibitors targeting Hsp90$\alpha$ and Grp94. The results showed that hydrogen bond interaction and hydrophobicity are crucial for the selective inhibition of Hsp90$\alpha$, while Grp94 specificity mainly relies on a typical hydrophobic cavity. These findings would provide the theoretical basis for the future development of novel selective inhibitors of Hsp90$\alpha$ and Grp94.

We have proposed a parallel simulated annealing using genetic crossover as one of powerful conformational search methods, in order to find the global minimum energy structures for protein systems. The simulated annealing using genetic crossover method, which incorporates the attractive features of the simulated annealing and the genetic algorithm, is useful for finding a minimum potential energy conformation of protein systems. However, when we perform simulations by using this method, we often find obviously unnatural stable conformations, which have "knots" of a string of an amino-acid sequence. Therefore, we combined knot theory with our simulated annealing using genetic crossover method in order to avoid the knot conformations from the conformational search space. We applied this improved method to protein G, which has 56 amino acids. As the result, we could perform the simulations, which avoid knot conformations.

In this article, basing ensemble theory, the numerical form of time autocorrelation function and its integration which are usually used in molecular simulation is derived from its fundamental definition. In order to verify the formula, the zero shear viscosity and self-diffusion coefficient are simulated and its results are at close quarters. It will be a useful reference for the application of time autocorrelation function in molecular simulation.

Recently, the computer simulation of molecular imprinted polymer (MIP) has been suggested as a rational method to search for optimal imprinting conditions in environmental science and engineering. In this paper, the sulfisoxazole conformation was optimized and sulfisoxazole and the functional monomers were computed using quantum chemistry method at MP2 level with 6-31++G* basis set. The binding energy, ΔE, an important parameter for their interactions, was used to select the best functional monomers, and the solvation energy was used to choose the most suitable solvent. The results indicated that the best functional monomer was acrylic acid, the most suitable solvent was carbon tetrachloride, and the most stable molecular model was the hydrogen bond formed between the H18 in sulfisoxazole and the O2 in acrylic acid with 1:1 molar ratio of SIZ to AA. These results had an insight into the interaction of the sulfisoxazole MIP, which provided theoretical reference for SIZ-MIP.