Current Proteomics最新文献

{"title":"The epidemiological and pangenome landscape of Staphylococcus aureus and identification of conserved novel candidate vaccine antigens","authors":"Kanwal Naz, Nimat Ullah, Anam Naz, Sidra Irum, H. Dar, Tahreem Zaheer, F. Shahid, Amjad Ali","doi":"10.2174/1570164618666210212122847","DOIUrl":"https://doi.org/10.2174/1570164618666210212122847","url":null,"abstract":"\u0000\u0000 Staphylococcus aureus (S. aureus) is a gram-positive bacterium and one of the major nosocomial pathogen. It has the ability to acquire resistance against almost all available classes of antibiotics; Methicillin-Resistant S. aureus (MRSA) is a well-known antibiotic resistance. S. aureus is a globally distributed pathogen that need in-depth epidemiological and genomic level investigation for proper treatment and prevention. \u0000\u0000\u0000\u0000 To explore the genomic epidemiology of S. aureus in-silico Multi Locus Sequence Typing (MLST) was carried out for 355 complete genomes. Diversity within the species was investigated through pan-genome analysis and subtractive genomic approach was employed for identification of core immunogenic targets. \u0000\u0000\u0000\u0000 Epidemiological study identified 62 different sequence types (STs) of S. aureus distributed worldwide, in which ST-8, ST-5, ST-398, ST-239, and ST-30 are the most dominant STs comprising more than 50% of the isolates. The pan-genome of S. aureus is still open with 7,199 genes and there is a major contribution (80%) of MRSA strains in the S. aureus species pangenome. The core genome (2,025 genes) of S. aureus is almost stable (comprises of 72% of S. aureus genome size) while accessory and unique genes (28% of S. aureus genome size) are gradually increasing. Screening of 2,025 core genes identified putative vaccine candidates. The best scoring and dominant B-cell and T-cell epitopes were predicted out of the selected potential vaccine candidate proteins with the help of a multi-step screening procedure. \u0000\u0000\u0000\u0000 We believe that the current study will provide insight into the genetic epidemiology and diversity of S. aureus and the predicted epitopes against the pathogen can be tested further for its immunological responses within the host and may provide both humoral and cellular immunity against the disease.\u0000","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"47 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2021-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85294841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective inhibition of mitochondrial metabolism by Cryptotanshinone in MDA-MB231 cells : A Proteomic Analysis","authors":"Jiefeng Zhou, Qingcao Li, Haoran Wu, Shin-Han Tsai, Yu-Ting Yeh","doi":"10.2174/1570164618666210208144542","DOIUrl":"https://doi.org/10.2174/1570164618666210208144542","url":null,"abstract":"\u0000\u0000\u0000Triple-negative breast cancer (TNBC) is a subtype of invasive cancer in breast with the symptoms of unfavourable prognosis and limited targeted treatment options. Evidence of changes in the metabolic status of TNBC, characterised by increased glycolysis, mitochondrial oxidative phosphorylation, as well as production and utilization of tricarboxylic acid cycle intermediates.\u0000\u0000\u0000\u0000\u0000Investigate the proteins altered in cryptotanshinone treated MDA-MB-231 cells and explore the key pathways and specific molecular markers involved in cryptotanshinone treatment.\u0000\u0000\u0000\u0000\u0000We use unlabeled quantitative proteomics to gain insight into the anticancer mechanism of cryptotanshinone on MDA-MB231 triple negative breast cancer cells. And flow cytometry was used to detect apoptosis and changes in cell mitochondrial membrane potential.\u0000\u0000\u0000\u0000\u0000We show that inhibiting the expression of electron transport chain complex proteins, also inhibits mitochondrial oxidative phosphorylation. Additionally, down-regulation of the ribosime biogenesis pathway was found to inhibit cell metabolism. \u0000\u0000\u0000\u0000\u0000In summary, results show that cryptotanshinone can trigger rapid and irreversible apoptosis in MDA-MB-231 cells through effectively inhibiting cell metabolism.\u0000\u0000","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"18 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2021-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74116868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression Analysis of 4-Hydroxynonenal Modified Proteins in Schizophrenia Brain; Relevance to Involvement in Redox Dysregulation","authors":"S. Manzoor, A. Khan, Beena Hasan, Shamim Mushtaq, N. Ahmed","doi":"10.2174/1570164618666210121151004","DOIUrl":"https://doi.org/10.2174/1570164618666210121151004","url":null,"abstract":"Oxidative damage contributes to the pathophysiology of schizophrenia (SZ). Redox imbalance may\u0000lead to increased lipid peroxidation, which produces toxic aldehydes like 4-hydroxynonenal (4-HNE) ultimately leading to\u0000oxidative stress. Conversely, implications of oxidative stress points towards an alteration in HNE-protein adducts and\u0000activities of enzymatic and antioxidant systems in schizophrenia.\u0000\u0000\u0000\u0000Present study focuses on identification of HNE-protein adducts and its related molecular consequences in\u0000schizophrenia pathology due to oxidative stress, particularly lipid peroxidation.\u0000\u0000\u0000\u0000 Oxyblotting was performed on seven autopsied brain samples each from cortex and hippocampus\u0000region of schizophrenia patients and their respective normal healthy controls. Additionally, thiobarbituric acid substances\u0000(TBARS), reduced glutathione (GSH) levels and catalase (CAT) activities associated with oxidative stress, were also\u0000estimated.\u0000\u0000\u0000\u0000Obtained results indicates substantially higher levels of oxidative stress in schizophrenia patients than healthy\u0000control group represented by elevated expression of HNE-protein adducts. Interestingly, hippocampus region of\u0000schizophrenia brain shows increased HNE protein adducts compared to cortex. An increase in catalase activity (4.8876 ±\u00001.7123) whereas decrease in antioxidant GSH levels (0.213 ± 0.015µmol/ml) have been observed in SZ brain. Elevated\u0000TBARS level (0.3801 ± 0.0532ug/ml) were obtained in brain regions SZ patients compared with their controls that reflects\u0000an increased lipid peroxidation (LPO).\u0000\u0000\u0000\u0000Conclusion: We propose the role of HNE modified proteins possibly associated with the pathology of\u0000schizophrenia. Our data revealed increase lipid peroxidation as a consequence of increased TBARS production.\u0000Furthermore, altered cellular antioxidants pathways related to GSH and CAT also highlight the involvement of oxidative\u0000stress in schizophrenia pathology.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"141 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2021-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80061153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Technologies and their Application for Ensuring Meat Quality, Safety and Authenticity","authors":"R. Banerjee, N. B. Maheswarappa, K. Mohan, S. Biswas, S. Batabyal","doi":"10.2174/1570164618666210114113306","DOIUrl":"https://doi.org/10.2174/1570164618666210114113306","url":null,"abstract":"\u0000\u0000Proteomic tools were extensively used to understand the relationship between muscle proteome and conversion of\u0000muscle to meat, post-mortem proteolysis, meat texture, and variation in meat color. Developments in proteomic tools have\u0000also resulted in their application for addressing the safety and authenticity issues including meat species identification,\u0000detection of animal by-products, non-meat ingredients and tissues in meat products, traceability, identification of genetically\u0000modified ingredients, chemical residues and other harmful substances. Proteomic tools are also being used in some of the\u0000potential areas like understanding the effect of animal transportation, stunning, slaughter stress, halal authentication and\u0000issues related to animal welfare. Emerging advances in proteomic and peptidomic technologies and their application in\u0000traceability, meat microbiology, safety and authentication is taking a major stride as an interesting and complementary\u0000alternative to DNA based methods currently in use. Future research in meat science need to be linked to emerging\u0000metabolomic, lipidomic and other omic technologies for ensuring integrated meat quality and safety management. In this\u0000paper, a comprehensive overview of the use of proteomics for the assessment of quality and safety in meat value chain and\u0000their potential application is discussed.\u0000","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"96 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2021-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75238463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin Reverts the Protein Differential Expression in the Liver of the Diabetic Obese db/db mice","authors":"Oscar Gerardo Silva-Gaona, J. M. Guzmán-Flores, M. Hernández-Ortiz, K. Vargas-Ortiz, J. Ramírez-Emiliano, S. Encarnación-Guevara, V. Pérez-Vázquez","doi":"10.2174/1570164618666210114112642","DOIUrl":"https://doi.org/10.2174/1570164618666210114112642","url":null,"abstract":"\u0000\u0000 In type 2 diabetic mouse liver, hyperglycemia, and insulin modify gene expression. Curcumin is a\u0000powerful antioxidant and antidiabetic agent that regulates the gene expression of different signaling pathways through\u0000various transcription factors. Therefore, we hypothesized that curcumin modifies the protein expression profile in the liver\u0000of diabetic db/db mice.\u0000\u0000\u0000\u0000To determine the effects of curcumin on the liver protein profile of diabetic db/db mice.\u0000\u0000\u0000\u0000\u0000db/db and wild type (WT) male mice were allocated in four groups, and they were fed for eight weeks. Three WT\u0000and three diabetic db/db mice received a standard diet (SD; WT and db/db groups, respectively); three WT and three\u0000diabetic db/db mice received a SD supplemented with 0.75 % (w/w) curcumin (WT+C and db/db+C groups, respectively).\u0000Liver proteins were separated by 2D electrophoresis. Differential protein expression analysis was performed on\u0000ImageMaster 2D Platinum software, and selected proteins were identified by MALDI-TOF-MS and subjected to enrichment\u0000analysis using STRING and DAVID databases.\u0000\u0000\u0000\u0000Thirty-six proteins with differential expression due to the diabetic background and curcumin treatment were found;\u0000these proteins participate in the metabolism of amino acids, carbohydrates, and lipids. Interestingly, the altered expression of\u0000seven proteins was prevented in the liver of the diabetic mice that received curcumin.\u0000\u0000\u0000\u0000Among all differentially expressed proteins, curcumin reverted the altered expression of seven proteins. Thus,\u0000although it was observed that curcumin did not affect the biochemical parameters, it does modify the expression of some\u0000liver proteins in diabetic mice.\u0000","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"40 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2021-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89033641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Proteomic Identification and Bioinformatics Analysis of Femoral Neck in Elderly Female Patients with Hyperuricaemia","authors":"Yi-feng He, Guang-xin Zhang, Yuyang Huang, Qi Li, Cheng Luo","doi":"10.2174/1570164618999210112203816","DOIUrl":"https://doi.org/10.2174/1570164618999210112203816","url":null,"abstract":"\u0000\u0000Serum uric acid (UA) is positively correlated with bone mineral density (BMD). However, the mechanism by which serum UA affects BMD remains unclear.\u0000\u0000\u0000\u0000The aim was carried out to search for the functional proteins related to serum UA and femoral neck BMD to better understand the pathophysiological mechanism of osteoporosis.\u0000\u0000\u0000\u0000In this study, patients in the UA group (hyperuricaemia combined with femoral neck fracture) and the control group (normal uricaemia combined with femoral neck fracture) were selected according to the inclusion criteria. Total protein was extracted from the femoral neck of each patient. Fluorescence differential gel electrophoresis was used to separate the total proteins, and the differentially expressed protein spots were detected by image analysis. After enzyme digestion, peptide mass fingerprinting and database searches were performed to identify the differentially expressed proteins. DAVID software and Kyoto Encyclopedia of Genes and Genomes (KEGG) data were used for enrichment analysis of the screened differential proteins.\u0000\u0000\u0000\u0000After mass spectrometry and database searching, 66 differentially expressed protein spots were identified between the UA group and the control group. Most differentially expressed proteins functioned in cytoskeleton formation, energy metabolism, or signal transduction. They were mainly involved in 50 biological processes, including peroxisome proliferator-activated receptor (PPAR) signalling and fatty acid metabolism. PPARγ and PLIN1 were subject to Western blotting analysis detection; results were consistent with the Label-Free result.\u0000\u0000\u0000\u0000Based on an analysis of the biological information, these proteins may be associated with the incidence and progression of the femoral neck bone tissues of hyperuricaemia patients.\u0000","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"132 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2021-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86816527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics-based characterization of proteins related to SARS-CoV-2 using the Polarity Index Method® (PIM®) and Intrinsic Disorder Predisposition","authors":"C. Polanco, V. Uversky, Guy W. Dayhoff, A. Huberman, T. Buhse, M. Márquez, G. Vargas-Alarcón, J. Castañón-González, Leire Andrés, J. Dı́az-González, Karina González-Bañales","doi":"10.2174/1570164618666210106114606","DOIUrl":"https://doi.org/10.2174/1570164618666210106114606","url":null,"abstract":"\u0000\u0000The global outbreak of the 2019 novel Coronavirus Disease (COVID-19) caused by the infection with the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which appeared in China at the end of\u00002019, signifies a major public health issue at the current time.\u0000\u0000\u0000\u0000 The objective of the present study is to characterize the physicochemical properties of the SARS-CoV-2 proteins at a residues level, and to generate a “bioinformatics fingerprint” in the form of a “PIM® profile” created for each\u0000sequence utilizing the Polarity Index Method® (PIM®), suitable for the identification of these proteins.\u0000\u0000\u0000\u0000Two different bioinformatics approaches were used to analyze sequence characteristics of these proteins at\u0000the residues level, an in-house bioinformatics system PIM®, and a set of the commonly used algorithms for the predic-tion of protein intrinsic disorder predisposition, such as PONDR® VLXT, PONDR® VL3, PONDR® VSL2, PONDR®\u0000FIT, IUPred_short and IUPred_long. The PIM® profile was generated for four SARS-CoV-2 structural proteins and\u0000compared with the corresponding profiles of the SARS-CoV-2 non-structural proteins, SARS-CoV-2 putative proteins,\u0000SARS-CoV proteins, MERS-CoV proteins, sets of bacterial, fungal, and viral proteins, cell-penetrating peptides, and a\u0000set of intrinsically disordered proteins. We also searched for the UniProt proteins with PIM® profiles similar to those of\u0000SARS-CoV-2 structural, non-structural, and putative proteins.\u0000\u0000\u0000\u0000We show that SARS-CoV-2 structural, non-structural, and putative proteins are characterized by a unique\u0000PIM® profile. A total of 1736 proteins were identified from the 562,253 “reviewed” proteins from the UniProt database,\u0000whose PIM® profile was similar to that of the SARS-CoV-2 structural, non-structural, and putative proteins.\u0000\u0000\u0000\u0000The PIM® profile represents an important characteristic that might be useful for the identification of proteins similar to SARS-CoV-2 proteins.\u0000","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"7 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2021-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79974461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Proteomic Analysis of Hydrogen Peroxide-induced Protein Expression in Streptococcus pneumoniae D39","authors":"Sungkyoung Lee, Myoung-Ro Lee, S. Bae, M. Kwak","doi":"10.2174/1570164618999210104223526","DOIUrl":"https://doi.org/10.2174/1570164618999210104223526","url":null,"abstract":"\u0000\u0000Streptococcus pneumoniae is a leading cause of human respiratory tract infection. Despite the lack\u0000of activities of antioxidative enzymes, including cytochromes, hemoproteins, and peroxidases/catalases, traits conferring the\u0000aerotolerant-anaerobic growth of this bacterium are conserved, with high efficacy of antioxidative actions, in an oxygen-rich\u0000environment.\u0000\u0000\u0000\u0000Through proteome analysis, this study’s intention was to evaluate differentially expressed proteins and/or gene\u0000products modeled in a highly virulent strain, S. pneumoniae D39, exogenously-treated with millimolar concentrations of\u0000H2O2.\u0000\u0000\u0000\u0000For two-dimensional gel electrophoresis (2-DE) analysis, following one dimensional isoelectric focusing with an\u0000immobilized pH gradient of pH 4-7, the most significantly mobilized proteins expressed were separated by SDS-PAGE in\u0000the second dimension. With a total of 431 protein spots detected, certain proteins were excised, in-gel trypsin digested, and\u0000analyzed by combination with MALDI-TOF and LC-ESI-MS/MS for mass spectrometric peptide mapping and protein\u0000identification. Utilizing mass spectrometry analysis of spots excised from 2-DE, the selected protein spots were identified\u0000with a variety of databases and MASCOT.\u0000\u0000\u0000\u0000With the aid of comparisons to proteome reference maps, the most differentially expressed 38 proteins, those with\u0000approximately 1.4-fold or more increase and/or decrease or with multiple isoforms exhibiting variable pI values, were\u0000induced by treatment of exogenous 2 mM H2O2. The identified proteins were seen to be involved in pneumococcal\u0000pathogenesis and primary metabolism, amongst others.\u0000\u0000\u0000\u0000This is the first study to convincingly document proteomic information associated with pathophysiological\u0000adaptation under the given oxidative conditions, and corresponding potential antioxidative mechanisms, in S. pneumoniae.\u0000","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"125 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2021-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83830879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of Nitration Sites Based on FCBF Method and Stacking Ensemble Model","authors":"Min Liu, Lu Zhang, Xinyi Qin, Tao Huang, Ziwei Xu, Guangzhong Liu","doi":"10.2174/1570164618999210101222637","DOIUrl":"https://doi.org/10.2174/1570164618999210101222637","url":null,"abstract":"Nitration is one of the important Post-Translational Modification (PTM) occurring on the tyrosine residues of proteins. The occurrence of protein tyrosine nitration under disease conditions is inevitable and represents a shift from the signal transducing physiological actions of -NO to oxidative and potentially pathogenic pathways. Abnormal protein nitration modification can lead to serious human diseases, including neurodegenerative diseases, acute respiratory distress, organ transplant rejection and lung cancer. It is necessary and important to identify the nitration sites in protein sequences. Predicting that which tyrosine residues in the protein sequence are nitrated and which are not is of great significance for the study of nitration mechanism and related diseases. In this study, a prediction model of nitration sites based on the over-under sampling strategy and the FCBF method was proposed by stacking ensemble learning and fusing multiple features. Firstly, the protein sequence sample was encoded by 2701-dimensional fusion features (PseAAC, PSSM, AAIndex, CKSAAP, Disorder). Secondly, the ranked feature set was generated by the FCBF method according to the symmetric uncertainty metric. Thirdly, in the process of model training, use the over- and under- sampling technique was used to tackle the imbalanced dataset. Finally, the Incremental Feature Selection (IFS) method was adopted to extract an optimal classifier based on 10-fold cross-validation. Results show that the model has significant performance advantages in indicators such as MCC, Recall and F1-score, no matter in what way the comparison was conducted with other classifiers on the independent test set, or made by cross-validation with single-type feature or with fusion-features on the training set. By integrating the FCBF feature ranking methods, over- and under- sampling technique and a stacking model composed of multiple base classifiers, an effective prediction model for nitration PTM sites was build, which can achieve a better recall rate when the ratio of positive and negative samples is highly imbalanced.","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"29 1","pages":"1-11"},"PeriodicalIF":0.8,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76870640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning-based Virtual Screening Strategy Reveals Some Natural Compounds As Potential PAK4 Inhibitors In Triple Negative Breast Cancer","authors":"Opeyemi Iwaloye, O. Elekofehinti, Babatomiwa Kikiowo, E. Oluwarotimi, T. M. Fadipe","doi":"10.2174/1570164618999201223092209","DOIUrl":"https://doi.org/10.2174/1570164618999201223092209","url":null,"abstract":"\u0000\u0000 P-21 activating kinase 4 (PAK4) is implicated in poor prognosis of many cancers, especially in the\u0000progression of Triple Negative Breast Cancer (TNBC). The present study was aimed at designing some potential drug\u0000candidates as PAK4 inhibitors for breast cancer therapy.\u0000\u0000\u0000\u0000This study aimed to finding novel inhibitors of PAK4 from natural compounds using computational approach.\u0000\u0000\u0000\u0000\u0000An e-pharmacophore model was developed from docked PAK4-coligand complex and used to screen over a\u0000thousand natural compounds downloaded from BIOFACQUIM and NPASS databases to match a minimum of 5 sites for\u0000selected (ADDDHRR) hypothesis. The robustness of the virtual screening method was accessed by well-established\u0000methods including EF, ROC, BEDROC, AUAC, and the RIE. Compounds with fitness score greater than one were filtered\u0000by applying molecular docking (HTVS, SP, XP and Induced fit docking) and ADME prediction. Using Machine learningbased approach QSAR model was generated using Automated QSAR. The computed top model kpls_des_17 (R2= 0.8028,\u0000RMSE = 0.4884 and Q2 = 0.7661) was used to predict the pIC50 of the lead compounds. Internal and external validations\u0000were accessed to determine the predictive quality of the model. Finally the binding free energy calculation was computed.\u0000\u0000\u0000\u0000The robustness/predictive quality of the models were affirmed. The hits had better binding affinity than the\u0000reference drug and interacted with key amino acids for PAK4 inhibition. Overall, the present analysis yielded three potential\u0000inhibitors that are predicted to bind with PAK4 better than reference drug tamoxifen. The three potent novel inhibitors\u0000vitexin, emodin and ziganein recorded IFD score of -621.97 kcal/mol, -616.31 kcal/mol and -614.95 kcal/mol, respectively\u0000while showing moderation for ADME properties and inhibition constant.\u0000\u0000\u0000\u0000It is expected that the findings reported in this study may provide insight for designing effective and less toxic\u0000PAK4 inhibitors for triple negative breast cancer.\u0000","PeriodicalId":50601,"journal":{"name":"Current Proteomics","volume":"33 1","pages":""},"PeriodicalIF":0.8,"publicationDate":"2020-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83944319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}