Effect of interface layer on the enhancement of thermal conductivity of SiC-Water nanofluids: Molecular dynamics simulation.

To investigate the impact of interfacial layer effects on the thermal conductivity of nanofluids and the microscopic mechanisms of enhanced thermal conductivity, this study employed non-equilibrium molecular dynamics to compute the thermal conductivity, number density, radial distribution function, and mean square displacement distribution of SiC nanofluids. The impact of nanoparticle volume fraction and particle size parameters on the thermal conductivity of nanofluids and the structure of interfacial adsorption layers was discussed. The simulation calculation results show that the coefficient of thermal conductivity of nanofluid is positively related to the volume fraction of nanoparticles, increasing from 0.6529 W/(m·K) to 0.8159 W/(m·K), and the enhancement of thermal conductivity by the volume fraction can be up to 33.97 %. The thermal conductivity is inversely correlated with the change in particle size, and the maximum improvement in thermal conductivity by particle size can reach up to 12.05 %. The simulated results of the thermal conductivity of nanofluid are almost consistent with the predicted results of the Yu&Choi model, and the error is controlled within 5 %. Simultaneously, the thickness of the interfacial adsorption layer decreases with an increase in particle size. This reduction arises due to larger particles having a smaller specific surface area, resulting in fewer particle surfaces covered by the interface layer. Moreover, the impact of particle size on the arrangement and affinity of molecules within the interface layer contributes to this decrease. Overall, interface layer effects exhibit a dual impact on the thermal conduction of nanofluids. The structured formation and high-density distribution of the adsorption layer contribute to enhanced heat transfer, while thermal resistance between nanoparticle surfaces and the fluid restricts heat transmission.

MC design and FIB preparation of a YSZ biochemical material microstructure.

Aiming at the difficulty of traditional machining of Y2O3-ZrO2 (YSZ) inert ceramic materials, a different method using focused ion beam to selectively create nanoscale microscale structures on the surface of materials was proposed. The sputtering yield, surface damage, and the energy loss of YSZ materials was investigated using the SRIM software using the Monte Carlo method. It is shown that the sputtering yield increases with ion energy in the range 0-30 keV, reaching a maximum of 9.4 atoms/ion at 30 keV. At an ion beam voltage of 30 keV, the most severe damage to the material is 8 mm on the surface. At the same time, the main forms of energy loss in the treatment are phonon energy loss and ionization energy loss, of which phonon energy loss due to the recoil atoms is the largest. In addition, we continue to perform focused ion beam processing experiments on YSZ materials, combining previous MC modeling to optimize different operating conditions such as ion beam, voltage and processing mode. The optimized processing parameters are 30 keV and 2.5 nA. It is shown that the quality of the deep grooves gradually improves with decreasing ion beam current at the same ion beam voltage. However, an excessively small ion beam current leads to an excessively large depth of the deep grooves and lengthy processing times.

Ginsenoside compound K protects against cerebral ischemia/reperfusion injury via Mul1/Mfn2-mediated mitochondrial dynamics and bioenergy.

Background: Ginsenoside compound K (CK), the main active metabolite in Panax ginseng, has shown good safety and bioavailability in clinical trials and exerts neuroprotective effects in cerebral ischemic stroke. However, its potential role in the prevention of cerebral ischemia/reperfusion (I/R) injury remains unclear. Our study aimed to investigate the molecular mechanism of ginsenoside CK against cerebral I/R injury. Methods: We used a combination of in vitro and in vivo models, including oxygen and glucose deprivation/reperfusion induced PC12 cell model and middle cerebral artery occlusion/reperfusion induced rat model, to mimic I/R injury. Intracellular oxygen consumption and extracellular acidification rate were analyzed by Seahorse multifunctional energy metabolism system; ATP production was detected by luciferase method. The number and size of mitochondria were analyzed by transmission electron microscopy and MitoTracker probe combined with confocal laser microscopy. The potential mechanisms of ginsenoside CK on mitochondrial dynamics and bioenergy were evaluated by RNA interference, pharmacological antagonism combined with co-immunoprecipitation analysis and phenotypic analysis. Results: Ginsenoside CK pretreatment could attenuate mitochondrial translocation of DRP1, mitophagy, mitochondrial apoptosis, and neuronal bioenergy imbalance against cerebral I/R injury in both in vitro and in vivo models. Our data also confirmed that ginsenoside CK administration could reduce the binding affinity of Mul1 and Mfn2 to inhibit the ubiquitination and degradation of Mfn2, thereby elevating the protein level of Mfn2 in cerebral I/R injury. Conclusion: These data provide evidence that ginsenoside CK may be a promising therapeutic agent against cerebral I/R injury via Mul1/Mfn2-mediated mitochondrial dynamics and bioenergy.

Accurate Cutting-Force Measurement with Smart Tool Holder in Lathe.

Cutting force in lathe work is closely related to tool wear and affects the turning quality. Direct measurement of the cutting force by measuring the strain of the tool holder is challenging because the tool holder design aims to be highly rigid in order to undertake large cutting forces. Accordingly, the most popular dynamometer designs modify the standard tool holder by decreasing the structural rigidity of the holder, which reduces the machining precision and is not widely accepted. In order to solve the issue of the low stiffness of the dynamometer reducing the machining precision, in this paper, the ultra-low strain on the tool holder was successfully detected by the highly sensitive semiconductor strain gauges (SCSG) adjacent to the blade cutting insert. However, the cutting process would generate much heat, which increases the force measuring area temperature of the tool holder by about 30 °C. As a result, the readout drifted significantly with the temperature changes due to the high temperature coefficient of SCSG. To solve this problem, the temperature on the tool holder was monitored and a BP neural network was proposed to compensate for temperature drift errors. Our methods improved the sensitivity (1.14 × 10-2 mV/N) and the average relative error of the BP neural network prediction (≤1.48%) while maintaining the original stiffness of the tool holder. The smart tool holder developed possesses high natural frequency (≥6 kHz), it is very suitable for dynamic cutting-force measurement. The cutting experiment data in the lathe work show comparable performance with the traditional dynamometers and the resolution of the smart tool holder is 2 N (0.25% of total range).

Recent advances in ginsenosides against respiratory diseases: Therapeutic targets and potential mechanisms.

BACKGROUND: Respiratory diseases mainly include asthma, influenza, pneumonia, chronic obstructive pulmonary disease, pulmonary hypertension, lung fibrosis, and lung cancer. Given their high prevalence and poor prognosis, the prevention and treatment of respiratory diseases are increasingly essential. In particular, the development for the novel strategies of drug treatment has been a hot topic in the research field. Ginsenosides are the major component of Panax ginseng C. A. Meyer (ginseng), a food homology and well-known medicinal herb. In this review, we summarize the current therapeutic effects and molecular mechanisms of ginsenosides in respiratory diseases. METHODS: The reviewed studies were retrieved via a thorough analysis of numerous articles using electronic search tools including Sci-Finder, ScienceDirect, PubMed, and Web of Science. The following keywords were used for the online search: ginsenosides, asthma, influenza, pneumonia, chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), lung fibrosis, lung cancer, and clinical trials. We summarized the findings and the conclusions from 176 manuscripts on ginsenosides, including research articles and reviews. RESULTS: Ginsenosides Rb1, Rg1, Rg3, Rh2, and CK, which are the most commonly reported ginsenosides for treating of respiratory diseases, and other ginsenosides such as Rh1, Rk1, Rg5, Rd and Re, all primarily reduce pneumonia, fibrosis, and inhibit tumor progression by targeting NF-κB, TGF-ß/Smad, PI3K/AKT/mTOR, and JNK pathways, thereby ameliorating respiratory diseases. CONCLUSION: This review provides novel ideas and important aspects for the future research of ginsenosides for treating respiratory diseases.

Panax ginseng against myocardial ischemia/reperfusion injury: A review of preclinical evidence and potential mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C. A. Meyer (P. ginseng) is effective in the prevention and treatment of myocardial ischemia-reperfusion (I/R) injury. The mechanism by which P. ginseng exerts cardioprotective effects is complex. P. ginseng contains many pharmacologically active ingredients, such as molecular glycosides, polyphenols, and polysaccharides. P. ginseng and each of its active components can potentially act against myocardial I/R injury. Myocardial I/R was originally a treatment for myocardial ischemia, but it also induced irreversible damage, including oxygen-containing free radicals, calcium overload, energy metabolism disorder, mitochondrial dysfunction, inflammation, microvascular injury, autophagy, and apoptosis. AIM OF THE STUDY: This study aimed to clarify the protective effects of P. ginseng and its active ingredients against myocardial I/R injury, so as to provide experimental evidence and new insights for the research and application of P. ginseng in the field of myocardial I/R injury. MATERIALS AND METHODS: This review was based on a search of PubMed, NCBI, Embase, and Web of Science databases from their inception to February 21, 2022, using terms such as "ginseng," "ginsenosides," and "myocardial reperfusion injury." In this review, we first summarized the active ingredients of P. ginseng, including ginsenosides, ginseng polysaccharides, and phytosterols, as well as the pathophysiological mechanisms of myocardial I/R injury. Importantly, preclinical models with myocardial I/R injury and potential mechanisms of these active ingredients of P. ginseng for the prevention and treatment of myocardial disorders were generally summarized. RESULTS: P. ginseng and its active components can regulate oxidative stress related proteins, inflammatory cytokines, and apoptosis factors, while protecting the myocardium and preventing myocardial I/R injury. Therefore, P. ginseng can play a role in the prevention and treatment of myocardial I/R injury. CONCLUSIONS: P. ginseng has a certain curative effect on myocardial I/R injury. It can prevent and treat myocardial I/R injury in several ways. When ginseng exerts its effects, should be based on the theory of traditional Chinese medicine and with the help of modern medicine; the clinical efficacy of P. ginseng in preventing and treating myocardial I/R injury can be improved.

Biotransformation, Pharmacokinetics, and Pharmacological Activities of Ginsenoside Rd Against Multiple Diseases.

Panax ginseng C.A. Mey. has a history of more than 4000 years and is widely used in Asian countries. Modern pharmacological studies have proved that ginsenosides and their compounds have a variety of significant biological activities on specific diseases, including neurodegenerative diseases, certain types of cancer, gastrointestinal disease, and metabolic diseases, in which most of the interest has focused on ginsenoside Rd. The evidentiary basis showed that ginsenoside Rd ameliorates ischemic stroke, nerve injury, cancer, and other diseases involved in apoptosis, inflammation, oxidative stress, mitochondrial damage, and autophagy. In this review, we summarized available reports on the molecular biological mechanisms of ginsenoside Rd in neurological diseases, cancer, metabolic diseases, and other diseases. We also discussed the main biotransformation pathways of ginsenoside Rd obtained by fermentation.

Addition of Nano CaF2@SiO2 and SiC Whiskers in Ceramic Tools for Wear Reduction and Improved Machinability.

The addition of CaF2@SiO2 and SiC whiskers to ceramic tools can improve their flexural strength and fracture toughness, reduce surface damage, and improve their cutting performance. The cutting experiments showed that under the same cutting conditions, the surface roughness of the workpiece processed with the Al2O3/TiC/SiC/CaF2@SiO2 (ATSC10) tool was significantly lower than that of the workpiece processed with the Al2O3/TiC/ SiC (ATS) tool. Additionally, the main cutting force and cutting temperature when cutting with the ATSC10 tool were lower by 30 and 31.7%, respectively. These results were attributed to the precipitation of CaF2 from the nanocoated particles during cutting and the formation of a uniform and continuous lubricating film on the surface of the tool. The wear on the front surface of the ATS tool was mainly adhesive, and that on the back tool surface was mainly abrasive. For ATSC10, the main forms of wear on the tool front surface were adhesive and abrasive, whereas the main form of wear on the tool back surface was abrasive with slight adhesive wear. The addition of nano-coated particles and whiskers improved the mechanical properties of the cutting tool while maintaining good cutting performance.

Gut Microbiota: Therapeutic Targets of Ginseng Against Multiple Disorders and Ginsenoside Transformation.

Panax ginseng, as the king of Chinese herb, has significant therapeutic effects on obesity, type 2 diabetes mellitus, fatty liver disease, colitis, diarrhea, and many other diseases. This review systematically summarized recent findings, which show that ginseng plays its role by regulating gut microbiota diversity, and gut microbiota could also regulate the transformation of ginsenosides. We conclude the characteristics of ginseng in regulating gut microbiota, as the potential targets to prevent and treat metabolic diseases, colitis, neurological diseases, cancer, and other diseases. Ginseng treatment can increase some probiotics such as Bifidobacterium, Bacteroides, Verrucomicrobia, Akkermansia, and reduce pathogenic bacteria such as Deferribacters, Lactobacillus, Helicobacter against various diseases. Meanwhile, Bacteroides, Eubacterium, and Bifidobacterium were found to be the key bacteria for ginsenoside transformation in vivo. Overall, ginseng can regulate gut microbiome diversity, further affect the synthesis of secondary metabolites, as well as promote the transformation of ginsenosides for improving the absorptivity of ginsenosides. This review can provide better insight into the interaction of ginseng with gut microbiota in multiple disorders and ginsenoside transformation.

D3PM: a comprehensive database for protein motions ranging from residue to domain.

BACKGROUND: Knowledge of protein motions is significant to understand its functions. While currently available databases for protein motions are mostly focused on overall domain motions, little attention is paid on local residue motions. Albeit with relatively small scale, the local residue motions, especially those residues in binding pockets, may play crucial roles in protein functioning and ligands binding. RESULTS: A comprehensive protein motion database, namely D3PM, was constructed in this study to facilitate the analysis of protein motions. The protein motions in the D3PM range from overall structural changes of macromolecule to local flip motions of binding pocket residues. Currently, the D3PM has collected 7679 proteins with overall motions and 3513 proteins with pocket residue motions. The motion patterns are classified into 4 types of overall structural changes and 5 types of pocket residue motions. Impressively, we found that less than 15% of protein pairs have obvious overall conformational adaptations induced by ligand binding, while more than 50% of protein pairs have significant structural changes in ligand binding sites, indicating that ligand-induced conformational changes are drastic and mainly confined around ligand binding sites. Based on the residue preference in binding pocket, we classified amino acids into "pocketphilic" and "pocketphobic" residues, which should be helpful for pocket prediction and drug design. CONCLUSION: D3PM is a comprehensive database about protein motions ranging from residue to domain, which should be useful for exploring diverse protein motions and for understanding protein function and drug design. The D3PM is available on www.d3pharma.com/D3PM/index.php .

Comparisons of Isolation Methods, Structural Features, and Bioactivities of the Polysaccharides from Three Common Panax Species: A Review of Recent Progress.

Panax spp. (Araliaceae family) are widely used medicinal plants and they mainly include Panax ginseng C.A. Meyer, Panax quinquefolium L. (American ginseng), and Panax notoginseng (notoginseng). Polysaccharides are the main active ingredients in these plants and have demonstrated diverse pharmacological functions, but comparisons of isolation methods, structural features, and bioactivities of these polysaccharides have not yet been reported. This review summarizes recent advances associated with 112 polysaccharides from ginseng, 25 polysaccharides from American ginseng, and 36 polysaccharides from notoginseng and it compares the differences in extraction, purification, structural features, and bioactivities. Most studies focus on ginseng polysaccharides and comparisons are typically made with the polysaccharides from American ginseng and notoginseng. For the extraction, purification, and structural analysis, the processes are similar for the polysaccharides from the three Panax species. Previous studies determined that 55 polysaccharides from ginseng, 18 polysaccharides from American ginseng, and 9 polysaccharides from notoginseng exhibited anti-tumor activity, immunoregulatory effects, anti-oxidant activity, and other pharmacological functions, which are mediated by multiple signaling pathways, including mitogen-activated protein kinase, nuclear factor kappa B, or redox balance pathways. This review can provide new insights into the similarities and differences among the polysaccharides from the three Panax species, which can facilitate and guide further studies to explore the medicinal properties of the Araliaceae family used in traditional Chinese medicine.

Modelling and Prediction of Cutting Temperature in the Machining of H13 Hard Steel of Transient Heat Conduction.

Cutting heat conduction undergoes three stages that include intensity transient-state, transient-state, and steady-states. Especially during machining with coated cutting tools, in the conduction process, cutting heat needs to pass through a few micron thick coatings and then flow into the tool body. This heat conduction presents typical non-Fourier heat conduction characteristics. This paper focuses on the cutting temperature in transient heat conduction with a coated tool. A new analytical model to characterize the thermal shock based on the non-Fourier heat conduction was proposed. The distribution of cutting temperature in mono-layer coated tools during the machining was then illustrated. The cutting temperature distribution predicted by the Fourier heat conduction model was employed to compare with that by non-Fourier heat conduction in order to reveal the non-Fourier heat conduction effect in transient heat conduction. The results show that the transient heat conduction analytical model is more suitable for the intensity transient-state and transient-state in the process of cutting heat conduction.

Neuroprotective Potentials of Panax Ginseng Against Alzheimer's Disease: A Review of Preclinical and Clinical Evidences.

Alzheimer's disease (AD), a neurodegenerative disorder, is a major health concern in the increasingly aged population worldwide. Currently, no clinically effective drug can halt the progression of AD. Panax ginseng C.A. Mey. is a well-known medicinal plant that contains ginsenosides, gintonin, and other components and has neuroprotective effects against a series of pathological cascades in AD, including beta-amyloid formation, neuroinflammation, oxidative stress, and mitochondrial dysfunction. In this review, we summarize the effects and mechanisms of these major components and formulas containing P. ginseng in neuronal cells and animal models. Moreover, clinical findings regarding the prevention and treatment of AD with P. ginseng or its formulas are discussed. This review can provide new insights into the possible use of ginseng in the prevention and treatment of AD.

Effect of the Characteristic Size and Content of Graphene on the Crack Propagation Path of Alumina/Graphene Composite Ceramics.

In this paper, the Voronoimosaic model and the cohesive element method were used to simulate crack propagation in the microstructure of alumina/graphene composite ceramic tool materials. The effects of graphene characteristic size and volume content on the crack propagation behavior of microstructure model of alumina/graphene composite ceramics under different interfacial bonding strength were studied. When the phase interface is weak, the average energy release rate is the highest as the short diameter of graphene is 10-50 nm and the long diameter is 1600-2000 nm. When the phase interface is strong, the average energy release rate is the highest as the short diameter of graphene is 50-100 nm and the long diameter is 800-1200 nm. When the volume content of graphene is 0.50 vol.%, the average energy release rate reaches the maximum. When the velocity load is 0.005 m s-1, the simulation result is convergent. It is proven that the simulation results are in good agreement with the experimental phenomena.

Substitution Effect of the Trifluoromethyl Group on the Bioactivity in Medicinal Chemistry: Statistical Analysis and Energy Calculations.

The substitution of methyl (Me or -CH3) by trifluoromethyl (TFM or -CF3) is frequently used in medicinal chemistry. However, the exact effect of -CH3/-CF3 substitution on bioactivity is still controversial. We compiled a data set containing 28 003 pairs of compounds with the only difference that -CH3 is substituted by -CF3, and the statistical results showed that the replacement of -CH3 with -CF3 does not improve bioactivity on average. Yet, 9.19% substitution of -CH3 by -CF3 could increase the biological activity by at least an order. A PDB survey revealed that -CF3 prefers Phe, Met, Leu, and Tyr, while -CH3 prefers Leu, Met, Cys, and Ile. If we substitute the -CH3 by -CF3 near Phe, His, and Arg, the bioactivity is most probably improved. We performed QM/MM calculations for 39 -CH3/-CF3 pairs of protein-ligand complexes and found that the -CH3/-CF3 substitution does achieve a large energy gain in some systems, although the mean energy difference is subtle, which is consistent with the statistical survey. The -CF3 substitution on the benzene ring could be particularly effective at gaining binding energy. The maximum improvements in energy achieved -4.36 kcal/mol by QM/MM calculation. Moreover, energy decompositions from MM/GBSA calculations showed that the large energy gains for the -CH3/-CF3 substitution are largely driven by the electrostatic energy or the solvation free energy. These findings may shed some light on the biological activity profile for -CH3/-CF3 substitution, which should be useful for further drug discovery and drug design.

Computational study of the substituent effect of halogenated fused-ring heteroaromatics on halogen bonding.

Halogen bonding (XB) has been applied in many fields from crystal engineering to medicinal chemistry. Compared with the well-studied XB of simple halogenated aromatics, little research has been done on the XB of halogenated fused-ring heteroaromatics, a prevalent substructure in organic compounds. With 1H-pyrrolo[3,2-b]pyridines (PPs) as examples of novel fused-ring heteroaromatics with hydrogen bond donor and acceptor and XB donor, the XB formed by the halogenated heteroaromatics was explored in this study. With 4 different substituents, viz., -CH3, -NH2, -F, and -CONH2, at different positions, 339 derivatives of brominated PP (Br-PP) were designed for calculating their electrostatic potential of the σ-hole of the halogen atom (VS,max) and binding energy with ammonia as XB acceptor (Eint) at M06-2X/6-311++G(d,p) level by PCM model in dichloromethane. The calculated VS,max values ranging from -1.3 to 35.1 kcal/mol and the calculated Eint ranging from -0.82 to -2.37 kcal/mol demonstrated that the XB is complicated and highly tunable. Noticeably, the electron-withdrawing substituents, especially at ortho-position, do not always increase the values of VS,max, while the electron-donating substituents do not always decrease VS,max. Similar results were observed from the calculation on 339 iodinated PPs at M06-2X/6-311++G(d,p) level. The complexity of the XB formed by the halogenated fused ring heteroaromatics indicated a great potential of tuning its strength by different substituents at different positions and revealed a necessity of quantum chemistry calculation for predicting the XB.Graphical abstract.

Influence of CaF2@Al2O3 on Cutting Performance and Wear Mechanism of Al2O3/Ti(C,N)/CaF2@Al2O3 Self-Lubricating Ceramic Tools in Turning.

This study aimed at improving the cutting performance of a ceramic tool to which were added solid lubricant particles. We prepared the self-lubricating ceramic tool by adding CaF2@Al2O3 instead of CaF2, and the self-lubricating ceramic tool with Al2O3 as matrix phase, Ti(C,N) as reinforcement phase. The properties of the ceramic tool with different contents of CaF2@Al2O3 and CaF2 were studied by turning 40Cr. Compared with the ceramic tool with 10 vol.% CaF2, the main cutting force and the cutting temperature of the ceramic tool with 10 vol.% CaF2@Al2O3 decreased by 67.25% and 38.14% respectively. The wear resistance and machining surface quality of the ceramic tool with CaF2@Al2O3 were better than the ceramic tool to which were directly added CaF2. The optimal content of CaF2@Al2O3 particles was determined to be 10 vol.%. The addition of CaF2@Al2O3 particles effectively reduces the adverse effect of direct addition of CaF2 particles on the ceramic tool, and plays a role in improving the cutting performance of the ceramic tool.

Bisindole alkaloids with nitric oxide inhibitory activities from an alcohol extract of the Isatis indigotica roots.

Eight bisindole alkaloids including six undescribed ones (1a/1b-5) were isolated from an alcohol extract of the Isatis indigotica roots. Their structures and absolute configurations were supported by extensive spectroscopic data analysis, including 1D, 2D NMR, HRESIMS data, specific rotation data, and comparison of the experimental and calculated ECD data. Compounds 1a and 1b were determined to be a pair of enantiomers with a ratio of approximately 1:1 by chiral-phase chromatography analysis while compound 4 was elucidated as a new type of bisindole alkaloid with the aglycone categorized as bis(indole-1'/3″-yl)methane. All the isolated compounds were tested for their nitric oxide (NO) inhibitory effects and 1-4 and 6 exhibited inhibitory effects with IC50 values ranging from 11.0 to 37.6 µM.

Four undescribed sulfur-containing indole alkaloids with nitric oxide inhibitory activities from Isatis tinctoria L. roots.

Four undescribed sulfur-containing indole alkaloids, isatisindigoticanines H, I and isatindigosides F, G along with three known analogues were obtained from Isatis tinctoria L. roots. Isatisindigoticanines H and I contained an unusual 1-(thiazol-4-yl)butane-1,2,3,4-tetraol moiety while isatindigosides F and G possessed a new 3-[3-(1H-indole-2-yl)azet-2-yl]-1H-indole skeleton. The putative biosynthetic pathways of isatisindigoticanines H, I and isatindigosides F, G are proposed. The isolated compounds showed nitric oxide inhibitory effects with IC50 values ranging from 4.3 to 70.3 µM.

Exploring Conformational Change of Adenylate Kinase by Replica Exchange Molecular Dynamic Simulation.

Replica exchange molecular dynamics (REMD) simulation is a popular enhanced sampling method that is widely used for exploring the atomic mechanism of protein conformational change. However, the requirement of huge computational resources for REMD, especially with the explicit solvent model, largely limits its application. In this study, the availability and efficiency of a variant of velocity-scaling REMD (vsREMD) was assessed with adenylate kinase as an example. Although vsREMD achieved results consistent with those from conventional REMD and experimental studies, the number of replicas required for vsREMD (30) was much less than that for conventional REMD (80) to achieve a similar acceptance rate (∼0.2), demonstrating high efficiency of vsREMD to characterize the protein conformational change and associated free-energy profile. Thus, vsREMD is a highly efficient approach for studying the large-scale conformational change of protein systems.