The acidic pH-induced structural changes in apo-CP43 by spectral methodologies and molecular dynamics simulations

Wang, Wang; Li, Xue; Wang, Qiuying; Zhang, Qingyan; Du, Linfang

doi:10.1016/j.molstruc.2017.09.082

Cited by 19 publications

(15 citation statements)

References 51 publications

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“…The assessment of the backbone Cα-RMSD value for each target–EGCG system is used to measure the structural stability in the MD simulation [51,52] as shown in Figure 6. As shown, most of the systems reached equilibrium after 5 ns when running a MD simulation with an average backbone Cα-RMSD of about 3 Å.…”

Section: Resultsmentioning

confidence: 99%

“…The systems first had their energy minimized using the steepest descent minimization method to limit the energy to 1000 Kcal/mol/nm [69]. Before the formal simulation, the complex system was carried out at both 100 ps NVT and NPT ensemble with 300 K temperature and 1 atm pressure [22,51]. The long-range electrostatic interactions were calculated using the PME (Particle Mesh Ewald) method and the hydrogen bonds were constrained using the LINCS (Linear Constraint Solver) algorithm.…”

Section: Methodsmentioning

confidence: 99%

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In Silico Investigation of the Anti-Tumor Mechanisms of Epigallocatechin-3-Gallate

Wang

Xiong

et al. 2019

Molecules

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The EGCG, an important component of polyphenol in green tea, is well known due to its numerous health benefits. We employed the reverse docking method for the identification of the putative targets of EGCG in the anti-tumor target protein database and these targets were further uploaded to public databases in order to understand the underlying pharmacological mechanisms and search for novel EGCG-associated targets. Similarly, the pharmacological linkage between tumor-related proteins and EGCG was manually constructed in order to provide greater insight into the molecular mechanisms through a systematic integration with applicable bioinformatics. The results indicated that the anti-tumor mechanisms of EGCG may involve 12 signaling transduction pathways and 33 vital target proteins. Moreover, we also discovered four novel putative target proteins of EGCG, including IKBKB, KRAS, WEE1 and NTRK1, which are significantly related to tumorigenesis. In conclusion, this work may provide a useful perspective that will improve our understanding of the pharmacological mechanism of EGCG and identify novel potential therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

In Silico Investigation of the Anti-Tumor Mechanisms of Epigallocatechin-3-Gallate

Wang

Xiong

et al. 2019

Molecules

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“…2A, the fluorescence intensity of Pin1-WT decreased gradually with the increase of temperature, data of mutants not shown, which indicated that the polarity around the tryptophan residues gradually increased in the unfolded process. Ordinarily, the F 350 /F 335 ratio was used to reflect the changes in the λ max of the fluorescence spectra (λ max = max emission wavelength) 11,22 . The increase of F 350 /F 335 ratio meant red-shift of λ max , conversely, the decrease of the ratio indicated blue-shift of λ max .…”

Section: Resultsmentioning

confidence: 99%

Insight into the structural stability of wild-type and histidine mutants in Pin1 by experimental and computational methods

Wang

Xiong

et al. 2019

Sci Rep

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Pin1, a polypeptide proline isomerase parvulin, plays a key role in Alzheimer’s disease (AD), common tumors and cancers. Two conservative histidine residues, His59 and His157, are important for maintaining the stability of the PPIase domain. Hence multiple spectral and computational techniques were performed to investigate the potential mechanism of two histidine residues. Thermal denaturation indicated that both residues His59 and His157 are not sensitive to the lower temperatures, while residue His59 is more sensitive to the higher temperatures than residue His157. Acidic denaturation suggested that influences of both residues His59 and His157 to acidic stability were the difference from Pin1-WT. ANS and RLS spectra hinted that there was no significant effect on hydrophobic change and aggregation by histidine mutations. The GndHCl-induced denaturation implied that residues His59 and His157 contributed the most to the chemical stability. MD simulations revealed that residues His59 and His157 mutations resulted in that the hydrogen bond network of the dual histidine motif was destroyed wholly. In summary, these histidine residues play an important role in maintaining the structural stability of the PPIase domain.

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“…RMSF value is considered as the criterion of the overall flexibility in MD simulation [38,39]. Moreover, we also investigated the motion of key residues of FXIIa interacted with inhibitors [35].…”

Section: Analysis Of the Admet Predictionmentioning

confidence: 99%

High-Throughput Docking and Molecular Dynamics Simulations towards the Identification of Potential Inhibitors against Human Coagulation Factor XIIa

Xue

Peng

et al. 2020

Computational and Mathematical Methods in Medicine

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Human coagulation factor XIIa (FXIIa) is a trypsin-like serine protease that is involved in pathologic thrombosis. As a potential target for designing safe anticoagulants, FXIIa has received a great deal of interest in recent years. In the present study, we employed virtual high-throughput screening of 500,064 compounds within Enamine database to acquire the most potential inhibitors of FXIIa. Subsequently, 18 compounds with significant binding energy (from -65.195 to -15.726 kcal/mol) were selected, and their ADMET properties were predicted to select representative inhibitors. Three compounds (Z1225120358, Z432246974, and Z146790068) exhibited excellent binding affinity and druggability. MD simulation for FXIIa-ligand complexes was carried out to reveal the stability and inhibition mechanism of these three compounds. Through the inhibition of activated factor XIIa assay, we tested the activity of five compounds Z1225120358, Z432246974, Z45287215, Z30974175, and Z146790068, with pIC50 values of 9.3∗10−7, 3.0∗10−5, 7.8∗10−7, 8.7∗10−7, and 1.3∗10−6 M, respectively; the AMDET properties of Z45287215 and Z30974175 show not well but have better inhibition activity. We also found that compounds Z1225120358, Z45287215, Z30974175, and Z146790068 could be more inhibition of FXIIa than Z432246974. Collectively, compounds Z1225120358, Z45287215, Z30974175, and Z146790068 were anticipated to be promising drug candidates for inhibition of FXIIa.

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The acidic pH-induced structural changes in apo-CP43 by spectral methodologies and molecular dynamics simulations

Cited by 19 publications

References 51 publications

In Silico Investigation of the Anti-Tumor Mechanisms of Epigallocatechin-3-Gallate

In Silico Investigation of the Anti-Tumor Mechanisms of Epigallocatechin-3-Gallate

Insight into the structural stability of wild-type and histidine mutants in Pin1 by experimental and computational methods

High-Throughput Docking and Molecular Dynamics Simulations towards the Identification of Potential Inhibitors against Human Coagulation Factor XIIa

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