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1.
Accuracy comparison of several common implicit solvent models and their implementations in the context of protein-ligand binding.
Katkova, EV, Onufriev, AV, Aguilar, B, Sulimov, VB
Journal of molecular graphics & modelling. 2017;:70-80
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Abstract
In this study several commonly used implicit solvent models are compared with respect to their accuracy of estimating solvation energies of small molecules and proteins, as well as desolvation penalty in protein-ligand binding. The test set consists of 19 small proteins, 104 small molecules, and 15 protein-ligand complexes. We compared predicted hydration energies of small molecules with their experimental values; the results of the solvation and desolvation energy calculations for small molecules, proteins and protein-ligand complexes in water were also compared with Thermodynamic Integration calculations based on TIP3P water model and Amber12 force field. The following implicit solvent (water) models considered here are: PCM (Polarized Continuum Model implemented in DISOLV and MCBHSOLV programs), GB (Generalized Born method implemented in DISOLV program, S-GB, and GBNSR6 stand-alone version), COSMO (COnductor-like Screening Model implemented in the DISOLV program and the MOPAC package) and the Poisson-Boltzmann model (implemented in the APBS program). Different parameterizations of the molecules were examined: we compared MMFF94 force field, Amber12 force field and the quantum-chemical semi-empirical PM7 method implemented in the MOPAC package. For small molecules, all of the implicit solvent models tested here yield high correlation coefficients (0.87-0.93) between the calculated solvation energies and the experimental values of hydration energies. For small molecules high correlation (0.82-0.97) with the explicit solvent energies is seen as well. On the other hand, estimated protein solvation energies and protein-ligand binding desolvation energies show substantial discrepancy (up to 10kcal/mol) with the explicit solvent reference. The correlation of polar protein solvation energies and protein-ligand desolvation energies with the corresponding explicit solvent results is 0.65-0.99 and 0.76-0.96 respectively, though this difference in correlations is caused more by different parameterization and less by methods and indicates the need for further improvement of implicit solvent models parameterization. Within the same parameterization, various implicit methods give practically the same correlation with results obtained in explicit solvent model for ligands and proteins: e.g. correlation values of polar ligand solvation energies and the corresponding energies in the frame of explicit solvent were 0.953-0.966 for the APBS program, the GBNSR6 program and all models used in the DISOLV program. The DISOLV program proved to be on a par with the other used programs in the case of proteins and ligands solvation energy calculation. However, the solution of the Poisson-Boltzmann equation (APBS program) and Generalized Born method (implemented in the GBNSR6 program) proved to be the most accurate in calculating the desolvation energies of complexes.
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Computational prediction of octanol-water partition coefficient based on the extended solvent-contact model.
Kim, T, Park, H
Journal of molecular graphics & modelling. 2015;:108-17
Abstract
The logarithm of 1-octanol/water partition coefficient (LogP) is one of the most important molecular design parameters in drug discovery. Assuming that LogP can be calculated from the difference between the solvation free energy of a molecule in water and that in 1-octanol, we propose a method for predicting the molecular LogP values based on the extended solvent-contact model. To obtain the molecular solvation free energy data for the two solvents, a proper potential energy function was defined for each solvent with respect to atomic distributions and three kinds of atomic parameters. Total 205 atomic parameters were optimized with the standard genetic algorithm using the training set consisting of 139 organic molecules with varying shapes and functional groups. The LogP values estimated with the two optimized solvation free energy functions compared reasonably well with the experimental results with the associated squared correlation coefficient and root mean square error of 0.824 and 0.697, respectively. Besides the prediction accuracy, the present method has the merit in practical applications because molecular LogP values can be computed straightforwardly from the simple potential energy functions without the need to calculate various molecular descriptors. The methods for enhancing the accuracy of the present prediction model are also discussed.
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In vitro anti cancer activity of ethanol extract fractions of Aerva lanata L.
Bhanot, A, Sharma, R, Singh, S, Noolvi, MN, Singh, S
Pakistan journal of biological sciences : PJBS. 2013;(22):1612-7
Abstract
To explore in vitro anticancer potential of Aerva lanata L. (flowering aerial part). The study was performed with 5 different human cell lines for the study of lung, leukaemia, prostate, colon and cervix cancer by using Sulphorhodamine B (SRB) assay. There were three doses of 10, 30 and 100 microg mL(-1) of each Aerva lanata L. Chloroform fraction (ALCF) and Aerva lanata L. Ethyl Acetate Fraction (ALEAF) used in this study. ALCF showed significant % inhibitory effect for leukaemia, lung and colon cancer at maximum concentration of 100 microg mL(-1) as compared to standard drug mitomycin. On the other hand ALEAF showed the significant % inhibitory effect for lung and cervix cancer at maximum concentration of 100 microg mL(-1) as compared to standard drug 5-fluoro Uracil (5-FU). From the above studies it is concluded that, the ethyl acetate fraction and chloroform fraction of Aerva lanata L. provide enough experimental evidence for anticancer activity and these fractions could be useful in medical care.
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In vitro anti-oxidative activities and GC-MS analysis of various solvent extracts of Cassia singueana parts.
Ibrahim, MA, Koorbanally, NA, Islam, MS
Acta poloniae pharmaceutica. 2013;(4):709-19
Abstract
The present study was conducted to investigate the anti-oxidative activities of different solvent extracts of Cassia singueana parts. Our results indicate that all the extracts have reducing power (Fe3+ --> Fe2+) and DPPH radical scavenging abilities. However, the ethyl acetate extract of the stem bark has the highest total reducing power whilst the ethanol extract of the stem bark has more potent free radical scavenging activity than all the other extracts. The ethyl acetate extract of the stem bark exhibited more powerful hydroxyl radical scavenging activity than other extracts whilst the aqueous extract of the leaves displayed more potent nitric oxide inhibition activity than other extracts. The GC-MS analysis of the ethyl acetate extract of the stem bark and the ethanol extract of the root and leaves indicated that several aromatic compounds, including phenolics, fatty acids, amino acids and triterpenoids were present in these extracts. Data from this study suggest that the parts of C. singueana possessed anti-oxidative activities and can be used as a potential alternative medicine for oxidative stress related non-communicable chronic diseases. Further experimental and clinical studies in this regard are warranted.
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Ethanol-wet bonding may improve root dentine bonding performance of hydrophobic adhesive.
Pei, D, Huang, X, Huang, C, Wang, Y, Ouyang, X, Zhang, J
Journal of dentistry. 2012;(5):433-41
Abstract
OBJECTIVES The current study aimed to assess ethanol-wet dentine surfaces by atomic force microscopy (AFM), and to evaluate the efficacy of ethanol-wet bonding on root dentine by determining the shear bond strength (SBS) and interfacial nanoleakage expression. METHODS Flat dentine slices from human premolar roots were randomly grouped into five. All specimens were acid-etched, rinsed, and left moist. They were then treated with 100% ethanol for 0s (control group), 20s (Group 1), 60s (Group 2), three 60s periods (Group 3), or stepwise ethanol application (Group 4). After treatment, each group was bonded either with Adper™ Scotchbond™ Multi-Purpose (Scotchbond) or experimental hydrophobic adhesive. Nano-scale adhesion forces (Fad) were probed by AFM and analysed using one-way ANOVA. The SBS results were analysed using two-way ANOVA. Tukey's test was employed for multiple comparisons. RESULTS Ethanol-wet protocols significantly decreased the value of Fad (p<0.001). When bonded with Scotchbond, ethanol treatment did not affect the bond strength (p>0.05), but decreased the interfacial nanoleakage. The SBS values of the groups bonded with hydrophobic adhesive varied with different ethanol-wet protocols (p<0.05). Decreased nanoleakage was manifested in all experimental groups, except Group 1. Compared with the classical water-wet bonding with Scotchbond in the control group, Group 4 bonded with hydrophobic adhesive exhibited a significantly higher bond strength (p<0.05). CONCLUSIONS Ethanol-wet bonding using a stepwise ethanol application protocol may have potential benefits in the root dentine bonding of hydrophobic adhesive.
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Resin-dentin bonds to EDTA-treated vs. acid-etched dentin using ethanol wet-bonding. Part II: Effects of mechanical cycling load on microtensile bond strengths.
Sauro, S, Toledano, M, Aguilera, FS, Mannocci, F, Pashley, DH, Tay, FR, Watson, TF, Osorio, R
Dental materials : official publication of the Academy of Dental Materials. 2011;(6):563-72
Abstract
OBJECTIVE To compare microtensile bond strengths (MTBS) subsequent to load cycling of resin bonded acid-etched or EDTA-treated dentin using a modified ethanol wet-bonding technique. METHODS Flat dentin surfaces were obtained from extracted human molars and conditioned using 37% H(3)PO(4) (PA) (15s) or 0.1M EDTA (60s). Five experimental adhesives and one commercial bonding agent were applied to the dentin and light-cured. Solvated experimental resins (50% ethanol/50% comonomers) were used as primers and their respective neat resins were used as the adhesives. The resin-bonded teeth were stored in distilled water (24h) or submitted to 5000 loading cycles of 90N. The bonded teeth were then sectioned in beams for MTBS. Modes of failure were examined by scanning electron microscopy. RESULTS The most hydrophobic resin 1 gave the lowest bond strength values to both acid and EDTA-treated dentin. The hydrophobic resin 2 applied to EDTA-treated dentin showed lower bond strengths after cycling load but this did not occur when it was bonded to PA-etched dentin. Resins 3 and 4, which contained hydrophilic monomers, gave higher bond strengths to both EDTA-treated or acid-etched dentin and showed no significant difference after load cycling. The most hydrophilic resin 5 showed no significant difference in bond strengths after cycling loading when bonded to EDTA or phosphoric acid treated dentin but exhibited low bond strengths. SIGNIFICANCE The presence of different functional monomers influences the MTBS of the adhesive systems when submitted to cyclic loads. Adhesives containing hydrophilic comonomers are not affected by cycling load challenge especially when applied on EDTA-treated dentin followed by ethanol wet bonding.
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Effects of ethanol-wet bonding technique on root dentine adhesion.
Duan, SS, Ouyang, XB, Pei, DD, Huo, YH, Pan, QH, Huang, C
The Chinese journal of dental research. 2011;(2):105-11
Abstract
OBJECTIVE To investigate the effects of ethanol-wet bonding on the adhesion of experimental hydrophobic and commercial hydrophilic adhesives to root dentine. METHODS A total of 43 single-rooted integrated human premolars were selected and sectioned. Of the 86 initially obtained specimens, 66 were randomly and equally divided into water-wet bonding and ethanol-wet bonding groups (n = 33). The specimens of each group were subdivided into three subgroups (n = 11) based on different adhesives: two experimental hydrophobic adhesives (Bis-GMA/TEGDMA, BT; and UDMA/TEGDMA, UT) and one commercial hydrophilic adhesive (Adper™ Single Bond 2, SB). The root surfaces were ground, acid-etched and rinsed and resin composite applied. After storing in distilled water for 24 h at 37°C, the shear bond strength (SBS) of each specimen was measured. A sample from each subgroup was randomly selected and prepared for scanning electron microscopy (SEM) analysis. The remaining 20 specimens were used in the contact angle (CA) experiment, and the values of CA were measured. SBS was analysed with two-way ANOVA/Tukey's multiple comparison test and CA with independent sample t test. RESULTS A significant increase in SBS to root dentine was observed in the ethanol-wet bonding group compared with the traditional water-wet bonding group. The experimental hydrophobic adhesives (UT group) with ethanol-wet bonding presented the highest SBS (22.44 ± 3.32 MPa). CA increased significantly after the dentine surfaces were dried, especially for the water-saturated group. CONCLUSION The adhesion to root dentine surfaces with ethanol-wet bonding may be superior to water-wet bonding.
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Bonding ability of three ethanol-based adhesives after thermal fatigue.
Perdigão, J, Gomes, G, Sezinando, A
American journal of dentistry. 2011;(3):159-64
Abstract
PURPOSE To study the effect of thermal fatigue on the microTBS and interfacial morphology of three ethanol-based etch-&-rinse 2-bottle adhesives. METHODS microTBS - 24 third molars were randomly assigned to one of three adhesive systems: (1) Adper Single Bond Plus (SBP, 3M ESPE); (2) Ambar (AMB, FGM); (3) Excite (EXC, Ivoclar Vivadent), and restored with a hybrid resin composite. For each adhesive, half of the specimens were thermocycled (TC) for 20,000 cycles (5-55 degrees C) while the other half was kept in distilled water for 24 hours at 37 degreesC (control). Specimens were sectioned in X and Y directions and the resulting sticks were tested to failure in tension mode at a crosshead speed of 1 mm/minute. Statistical analysis was computed using ANOVA and Tukey's post hoc for the microTBS; and non-parametric cross-tabulation with Chi-Square for the pre-testing failures at P< 0.05. Interfacial morphology -The occlusal enamel was removed from 12 extracted molars perpendicular to the long axis of the tooth. Teeth were equally assigned to one of the three adhesives and restored with a 1 mm-thick layer of a hybrid composite resin. A 2 mm-thick disk was sectioned from each specimen and cross-sectioned in two identical halves. Half of the each specimen was TC for 20,000 cycles (5-55 degrees C) while the other half was kept in distilled water for 24 hours at 37 degrees C (control). Specimens were chemically challenged and prepared for FESEM observation to observe the integrity of the hybrid layer before and after thermal fatigue. Micrographs were recorded digitally at standard magnifications and measurements were taken with the microscope embedded image software. RESULTS microTBS - SBP and AMB resulted in statistically similar mean microTBS regardless of thermal fatigue. EXC resulted in statistically lower mean microTBS than SBP and AMB for the control (P< 0.001) and for the TC specimens (P< 0.0001). Interfacial morphology - The hybrid layers of SBP and AMB were densely infiltrated without interfacial failure. For EXC, extensive areas of debonding were observed between the adhesive layer and the hybrid layer both for the control and the TC groups. Thermal fatigue did not influence the bonding ability of AMB and SBP, but was detrimental for EXC.
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Six-month evaluation of adhesives interface created by a hydrophobic adhesive to acid-etched ethanol-wet bonded dentine with simplified dehydration protocols.
Sadek, FT, Mazzoni, A, Breschi, L, Tay, FR, Braga, RR
Journal of dentistry. 2010;(4):276-83
Abstract
OBJECTIVES To evaluate the efficacy of simplified dehydration protocols, in the absence of tubular occlusion, on bond strength and interfacial nanoleakage of a hydrophobic experimental adhesive blend to acid-etched, ethanol-dehydrated dentine immediately and after 6 months. METHODS Molars were randomly assigned to 6 treatment groups (n=5). Under pulpal pressure simulation, dentine crowns were acid-etched with 35% H(3)PO(4) and rinsed with water. Adper Scotchbond Multi-Purpose was used for the control group. The remaining groups had their dentine surface dehydrated with ethanol solutions: group 1=50%, 70%, 80%, 95% and 3x100%, 30s for each application; group 2 the same ethanol sequence with 15s for each solution; groups 3, 4 and 5 used 100% ethanol only, applied in seven, three or one 30s step, respectively. After dehydration, a primer (50% BisGMA+TEGDMA, 50% ethanol) was used, followed by the neat comonomer adhesive application. Resin composite build-ups were then prepared using an incremental technique. Specimens were stored for 24h, sectioned into beams and stressed to failure after 24h or after 6 months of artificial ageing. Interfacial silver leakage evaluation was performed for both storage periods (n=5 per subgroup). RESULTS Group 1 showed higher bond strengths at 24h or after 6 months of ageing (45.6+/-5.9(a)/43.1+/-3.2(a)MPa) and lower silver impregnation. Bond strength results were statistically similar to control group (41.2+/-3.3(ab)/38.3+/-4.0(ab)MPa), group 2 (40.0+/-3.1(ab)/38.6+/-3.2(ab)MPa), and group 3 at 24h (35.5+/-4.3(ab)MPa). Groups 4 (34.6+/-5.7(bc)/25.9+/-4.1(c)MPa) and 5 (24.7+/-4.9(c)/18.2+/-4.2(c)MPa) resulted in lower bond strengths, extensive interfacial nanoleakage and more prominent reductions (up to 25%) in bond strengths after 6 months of ageing. CONCLUSIONS Simplified dehydration protocols using one or three 100% ethanol applications should be avoided for the ethanol-wet bonding technique in the absence of tubular occlusion, as they showed decreased bond strength, more severe nanoleakage and reduced bond stability over time.
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10.
Marginal adaptation of an etch-and-rinse adhesive with a new type of solvent in class II cavities after artificial aging.
Manhart, J, Trumm, C
Clinical oral investigations. 2010;(6):699-705
Abstract
This in vitro study evaluated the marginal adaptation of etch-and-rinse adhesives. Standardized class II cavities were cut in 40 human molars with one proximal box limited within enamel and one proximal box extending into dentin. Teeth were assigned randomly to five groups (n = 8) and restored with incrementally placed composite restorations. Five combinations were tested: G1, XP Bond + Ceram-X Mono; G2, P&B NT + Ceram-X Mono; G3, Optibond Solo Plus + Ceram-X Mono; R1, Syntac Classic + Tetric EvoCeram; R2, Scotchbond 1 XT + Z250. After finishing and polishing, teeth were stored for 48 h in water at 37°C before subjected to artificial aging by thermal stress (5/55°C; ×2,000; 30 s) and mechanical loading (50 N; ×50,000). Marginal adaptation of the restorations was evaluated in a SEM (×200) using a replica technique. Statistical analysis was performed with nonparametric test methods (p < 0.05). The percentages of "perfect margin" after aging ranged from 95.9% to 99.6% in enamel and 85.9% to 96.0% in dentin. "Marginal opening" was observed between 0.1% to 2.6% in enamel and 2.6% to 11.8% in dentin. In enamel and dentin, both, G3 showed significantly more gap formation than G1 and G2. Comparing marginal adaptation to enamel and dentin within each group yielded only for G1 no significant differences. Tert-butanol-based XP Bond showed excellent marginal adaptation in both enamel and dentin.