Vina-Carb: Improving Glycosidic Angles during Carbohydrate Docking

Molecular docking programs are primarily designed to align rigid, drug-like fragments into the binding sites of macromolecules and frequently display poor performance when applied to flexible carbohydrate molecules. A critical source of flexibility within an oligosaccharide is the glycosidic linkages. Recently, Carbohydrate Intrinsic (CHI) energy functions were reported that attempt to quantify the glycosidic torsion angle preferences. In the present work, the CHI-energy functions have been incorporated into the AutoDock Vina (ADV) scoring function, subsequently termed Vina-Carb (VC). Two user-adjustable parameters have been introduced, namely, a CHI- energy weight term (<i>chi_coeff</i>) that affects the magnitude of the CHI-energy penalty and a CHI-cutoff term (<i>chi_cutoff</i>) that negates CHI-energy penalties below a specified value. A data set consisting of 101 protein–carbohydrate complexes and 29 apoprotein structures was used in the development and testing of VC, including antibodies, lectins, and carbohydrate binding modules. Accounting for the intramolecular energies of the glycosidic linkages in the oligosaccharides during docking led VC to produce acceptable structures within the top five ranked poses in 74% of the systems tested, compared to a success rate of 55% for ADV. An enzyme system was employed in order to illustrate the potential application of VC to proteins that may distort glycosidic linkages of carbohydrate ligands upon binding. VC represents a significant step toward accurately predicting the structures of protein–carbohydrate complexes. Furthermore, the described approach is conceptually applicable to any class of ligands that populate well-defined conformational states

Additional file 2: of Barriers and facilitators in providing oral health care to nursing home residents, from the perspective of care aides—a systematic review protocol

Search strategy. The file gives a list of search terms/keywords to be used for this protocol. (PDF 133 kb

Data_Sheet_2_Comprehensive Analysis of the Clinical and Biological Significances of Endoplasmic Reticulum Stress in Diffuse Gliomas.pdf

BackgroundAs a critical organelle for protein and lipid synthesis, the dysfunction of endoplasmic reticulum has a significant impact on multiple biological processes of cells. Thus, in this study, we constructed an ER stress-related risk signature to investigate the functional roles of ER stress in gliomas.MethodsA total of 626 samples from TCGA RNA-seq dataset (training cohort) and 310 samples from CGGA RNA-seq dataset (validation cohort) were enrolled in this study. Clinical information and genomic profiles were also obtained. The ER stress signature was developed by the LASSO regression model. The prognostic value of the risk signature was evaluated by Cox regression, Kaplan-Meier and ROC Curve analyses. Bioinformatics analysis and experiment in vitro were performed to explore the biological implication of this signature.ResultsWe found that the ER stress-related signature was tightly associated with major clinicopathological features and genomic alterations of gliomas. Kaplan-Meier curve and Cox regression analysis indicated that ER stress activation was an independent prognostic factor for patients with glioma. Besides, we also constructed an individualized prognosis prediction model through Nomogram and ROC Curve analysis. Bioinformatics analysis suggested that ER stress activation also promoted the malignant progression of glioma and participated in the regulation of tumor immune microenvironment, especially the infiltration of macrophages in M2 phase. These results were further validated in IHC analysis and cell biology experiments.ConclusionThe ER stress activation had a high prognostic value and could serve as a promising target for developing individualized treatment of glioma.</p

Data_Sheet_1_Comprehensive Analysis of the Clinical and Biological Significances of Endoplasmic Reticulum Stress in Diffuse Gliomas.PDF

BackgroundAs a critical organelle for protein and lipid synthesis, the dysfunction of endoplasmic reticulum has a significant impact on multiple biological processes of cells. Thus, in this study, we constructed an ER stress-related risk signature to investigate the functional roles of ER stress in gliomas.MethodsA total of 626 samples from TCGA RNA-seq dataset (training cohort) and 310 samples from CGGA RNA-seq dataset (validation cohort) were enrolled in this study. Clinical information and genomic profiles were also obtained. The ER stress signature was developed by the LASSO regression model. The prognostic value of the risk signature was evaluated by Cox regression, Kaplan-Meier and ROC Curve analyses. Bioinformatics analysis and experiment in vitro were performed to explore the biological implication of this signature.ResultsWe found that the ER stress-related signature was tightly associated with major clinicopathological features and genomic alterations of gliomas. Kaplan-Meier curve and Cox regression analysis indicated that ER stress activation was an independent prognostic factor for patients with glioma. Besides, we also constructed an individualized prognosis prediction model through Nomogram and ROC Curve analysis. Bioinformatics analysis suggested that ER stress activation also promoted the malignant progression of glioma and participated in the regulation of tumor immune microenvironment, especially the infiltration of macrophages in M2 phase. These results were further validated in IHC analysis and cell biology experiments.ConclusionThe ER stress activation had a high prognostic value and could serve as a promising target for developing individualized treatment of glioma.</p

Additional file 1: of Characterization, treatment and prognosis of retinoblastoma with central nervous system metastasis

Table S1. AJCC TNM Staging System. (DOCX 18 kb

SOCS3 methylation status in STS and LTS group and validiation cohort.

<p><b>A.</b> In the CGGA GBM cohort, the β values of the SOCS3 promoter of the two groups (STS group and LTS group) are significantly different (P<0.01). <b>B.</b> In an independent validation cohort, survival analysis showed that three groups divided by average methylation values are significantly different (P<0.04). <b>C.</b> In the TCGA GBM cohort, the group with β value>80 percent (red) has a significantly longer survival than the other four groups (P = 0.02).</p

Hypermethylation of SOCS3 promoter is consistent with G-CIMP.

<p><b>A.</b> In the CGGA samples, a ROC curve demonstrated a tight relationship between hypermethylation of the SOCS3 promoter and G-CIMP-positive status (AUC = 0.951, P = 0.001). <b>B.</b> In the TCGA samples, a similar relationship between hypermethylation of the SOCS3 promoter and G-CIMP-positive status is shown in the ROC curve (AUC = 0.943, P<0.001).</p

G-CIMP status in CGGA and TCGA cohort.

<p><b>A.</b> In the CGGA GBM cohort, the β values of the SOCS3 promoter of the two groups (G-CIMP-positive group and G-CIMP-negative group) displayed statistically significant difference (P<0.01). <b>B.</b> In the TGGA GBM cohort, the β values of the SOCS3 promoter of the two groups (G-CIMP-positive group and G-CIMP-negative group) also displayed statistically significant difference (P<0.01). <b>C.</b> In the G-CIMP-negative TCGA samples, there was no significant difference among the five groups (P = 0.60).</p

ALDH1A3: A Marker of Mesenchymal Phenotype in Gliomas Associated with Cell Invasion

<div><p>Aldehyde dehydrogenases (ALDH) is a family of enzymes including 19 members. For now, ALDH activity had been wildly used as a marker of cancer stem cells (CSCs). But biological functions of relevant isoforms and their clinical applications are still controversial. Here, we investigate the clinical significance and potential function of ALDH1A3 in gliomas. By whole-genome transcriptome microarray and mRNA sequencing analysis, we compared the expression of ALDH1A3 in high- and low- grade gliomas as well as different molecular subtypes. Microarray analysis was performed to identify the correlated genes of ALDH1A3. We further used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis to explore the biological function of ALDH1A3. Finally, by mRNA knockdown we revealed the relationship between ALDH1A3 and the ability of tumor invasion. ALDH1A3 overexpression was significantly associated with high grade as well as the higher mortality of gliomas in survival analysis. ALDH1A3 was characteristically highly expressed in Mesenchymal (Mes) subtype gliomas. Moreover, we found that ALDH1A3 was most relevant to extracellular matrix organization and cell adhesion biological process, and the ability of tumor invasion was suppressed after ALDH1A3 knockdown in vitro. In conclusion, ALDH1A3 can serve as a novel marker of Mes phenotype in gliomas with potential clinical prognostic value. The expression of ALDH1A3 is associated with tumor cell invasion.</p></div

Correlation of ALDH1A3 mRNA expression with tumor malignancy.

<p><b>A</b>. By genome-wide transcriptome microarray analysis, ALDH1A3 expressed higher in HGG (n = 179) than in LGG (n = 122) (p<0.0001). <b>B</b>. By whole transcriptome sequencing analysis, ALDH1A3 mRNA was overexpressed in HGG (n = 216) than in LGG (n = 109) (p<0.0001). Lines in the middle were the mean expression value. <b>C</b>. In TCGA whole transcriptome sequencing date, ALDH1A3 mRNA was overexpressed in HGG (n = 193) than in LGG (n = 374) (p<0.0001).</p