Bioinformatics and Biology Insights最新文献

{"title":"A Comprehensive Bioinformatics Approach to Identify Molecular Signatures and Key Pathways for the Huntington Disease.","authors":"Tahera Mahnaz Meem, Umama Khan, Md Bazlur Rahman Mredul, Md Abdul Awal, Md Habibur Rahman, Md Salauddin Khan","doi":"10.1177/11779322231210098","DOIUrl":"10.1177/11779322231210098","url":null,"abstract":"<p><p>Huntington disease (HD) is a degenerative brain disease caused by the expansion of CAG (cytosine-adenine-guanine) repeats, which is inherited as a dominant trait and progressively worsens over time possessing threat. Although HD is monogenetic, the specific pathophysiology and biomarkers are yet unknown specifically, also, complex to diagnose at an early stage, and identification is restricted in accuracy and precision. This study combined bioinformatics analysis and network-based system biology approaches to discover the biomarker, pathways, and drug targets related to molecular mechanism of HD etiology. The gene expression profile data sets GSE64810 and GSE95343 were analyzed to predict the molecular markers in HD where 162 mutual differentially expressed genes (DEGs) were detected. Ten hub genes among them (<i>DUSP1, NKX2-5, GLI1, KLF4, SCNN1B, NPHS1, SGK2, PITX2, S100A4</i>, and <i>MSX1</i>) were identified from protein-protein interaction (PPI) network which were mostly expressed as down-regulated. Following that, transcription factors (TFs)-DEGs interactions (FOXC1, GATA2, etc), TF-microRNA (miRNA) interactions (hsa-miR-340, hsa-miR-34a, etc), protein-drug interactions, and disorders associated with DEGs were predicted. Furthermore, we used gene set enrichment analysis (GSEA) to emphasize relevant gene ontology terms (eg, TF activity, sequence-specific DNA binding) linked to DEGs in HD. Disease interactions revealed the diseases that are linked to HD, and the prospective small drug molecules like cytarabine and arsenite was predicted against HD. This study reveals molecular biomarkers at the RNA and protein levels that may be beneficial to improve the understanding of molecular mechanisms, early diagnosis, as well as prospective pharmacologic targets for designing beneficial HD treatment.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"17 ","pages":"11779322231210098"},"PeriodicalIF":5.8,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systems Biology Approach for Investigating Significant Biomarkers and Drug Targets Common Among Patients with Gonorrhea, Chlamydia, and Prostate Cancer: A Pilot Study.","authors":"Abdulla Al Noman, Md Kobirul Islam, Tasmiah Feroz, Md Monir Hossain, Md Shahariar Kabir Shakil","doi":"10.1177/11779322231214445","DOIUrl":"10.1177/11779322231214445","url":null,"abstract":"<p><p>Having a previous history of sexually transmitted diseases (STDs) such as gonorrhea and chlamydia increases the chance of developing prostate cancer, the second most frequent malignant cancer among men. However, the molecular functions that cause the development of prostate cancer in persons with gonorrhea and chlamydia are yet unknown. In this study, we studied RNA-seq gene expression profiles using computational biology methods to find out potential biomarkers that could help us in understanding the patho-biological mechanisms of gonorrhea, chlamydia, and prostate cancer. Using statistical methods on the Gene Expression Omnibus (GEO) data sets, it was found that a total of 22 distinct differentially expressed genes were shared among these 3 diseases of which 14 were up-regulated (PGRMC1, TSC22D1, SH3BGRL, NNT, CTSC, FRMD3, CCR2, FAM210B, VCL, PTGS1, SLFN11, SLC40A1, PROS1, and DSE) and the remaining 8 genes were down-regulated (PRNP, HINT3, MARCKSL1, TMED10, SH3KBP1, ENSA, DERL1, and KMT2B). Investigation on these 22 unique dysregulated genes using Gene Ontology, BioCarta, KEGG, and Reactome revealed multiple altered molecular pathways, including regulation of amyloid precursor protein catabolic process, ferroptosis, effects on gene expression of <i>Homo sapiens</i> PPAR pathway, and innate immune system R-HSA-168249. Four significant hub proteins namely VCL, SH3KBP1, PRNP, and PGRMC1 were revealed by protein-protein interaction network analysis. By analyzing gene-transcription factors and gene-miRNAs interactions, significant transcription factors (POU2F2, POU2F1, GATA6, and HIVEP1) and posttranscriptional regulator microRNAs (hsa-miR-7-5p) were also identified. Three potential therapeutic compounds namely INCB3284, CCX915, and MLN-1202 were found to interact with up-regulated protein C-C chemokine receptor type 2 (CCR2) in protein-drug interaction analysis. The proposed biomarkers and therapeutic potential molecules could be investigated for potential pharmacological targets and activity in the fight against in patients with gonorrhea, chlamydia, and prostate cancer.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"17 ","pages":"11779322231214445"},"PeriodicalIF":5.8,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In Silico</i> Identification of Natural Food Compounds as Potential Quorum-Sensing Inhibitors Targeting the LasR Receptor of <i>Pseudomonas aeruginosa</i>.","authors":"Meryam Magri, El Mehdi Bouricha, Mohammed Hakmi, Rachid El Jaoudi, Lahcen Belyamani, Azeddine Ibrahimi","doi":"10.1177/11779322231212755","DOIUrl":"https://doi.org/10.1177/11779322231212755","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> is a major cause of nosocomial infections and is often associated with biofilm-mediated antibiotic resistance. The LasR protein is a key component of the quorum system in <i>P. aeruginosa</i>, allowing it to regulate its biofilm-induced pathogenicity. When the bacterial population reaches a sufficient density, the accumulation of N-(3-oxododecanoyl) acyl homoserine lactone (3O-C12-HSL) leads to the activation of the LasR receptor, which then acts as a transcriptional activator of target genes involved in biofilm formation and virulence, thereby increasing the bacteria's antibiotic resistance and enhancing its virulence. In this study, we performed a structure-based virtual screening of a natural food database of 10 997 compounds against the crystal structure of the ligand-binding domain of the LasR receptor (PDB ID: 3IX4). This allowed us to identify four molecules, namely ZINC000001580795, ZINC000014819517, ZINC000014708292, and ZINC000004098719, that exhibited a favorable binding mode and docking scores greater than -13 kcal/mol. Furthermore, the molecular dynamics simulation showed that these four molecules formed stable complexes with LasR during the 150-ns molecular dynamics (MD) simulation, indicating their potential for use as inhibitors of the LasR receptor in <i>P. aeruginosa</i>. However, further experimental validation is needed to confirm their activity.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"17 ","pages":"11779322231212755"},"PeriodicalIF":5.8,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Transcriptomics and Network Analysis of Potential Mechanisms and Health Effects of Convalescent COVID-19 Patients.","authors":"Suthipong Chujan,&nbsp;Watanyoo Nakareangrit,&nbsp;Tawit Suriyo,&nbsp;Jutamaad Satayavivad","doi":"10.1177/11779322231206684","DOIUrl":"10.1177/11779322231206684","url":null,"abstract":"<p><p>Coronaviral disease 2019 (COVID-19) is a recent pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, there are still cases of COVID-19 around the world that can develop into persistent symptoms after discharge. The constellation of symptoms, termed long COVID, persists for months and can lead to various diseases such as lung inflammation and cardiovascular disease, which may lead to considerable financial burden and possible risk to human health. Moreover, the molecular mechanisms underlying the post-pandemic syndrome of COVID-19 remain unclear. In this study, we aimed to explore the molecular mechanism, disease association, and possible health risks in convalescent COVID-19 patients. Gene expression data from a human convalescent COVID-19 data set was compared with a data set from healthy normal individuals in order to identify differentially expressed genes (DEGs). To determine biological function and potential pathway alterations, the GO and KEGG databases were used to analyze the DEGs. Disease association, tissue, and organ-specific analyses were used to identify possible health effects. A total of 250 DEGs were identified between healthy and convalescent COVID-19 subjects. The biological function alterations identified revealed cytokine interactions and increased inflammation through NF-κB1, RELA, JUN, STAT3, and SP1. Interestingly, the most significant pathways were cytokine-cytokine receptor interaction, altered lipid metabolism, and atherosclerosis that play a crucial role in convalescent COVID-19. In addition, we also found pneumonitis, dermatitis, and autoimmune diseases. Based on our study, convalescent COVID-19 is associated with inflammation in a variety of organs that could lead to autoimmune and inflammatory diseases, as well as atherosclerosis. These findings are a first step toward fully exploring the disease mechanisms in depth to understand the relationship between post-COVID-19 infection and potential health risks. This is necessary for the development of appropriate strategies for the prevention and treatment of long COVID.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"17 ","pages":"11779322231206684"},"PeriodicalIF":5.8,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1f/11/10.1177_11779322231206684.PMC10594973.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50160614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of Methyl-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxyhydrazide Derivatives as Potential Inhibitors of COVID-19 Main Protease: DFT and Molecular Docking Study.","authors":"Olawale Folorunso Akinyele,&nbsp;Emmanuel Gabriel Fakola,&nbsp;Omolara Olubunmi Adeboye,&nbsp;Sunday Chimela Chinuomah","doi":"10.1177/11779322231182050","DOIUrl":"10.1177/11779322231182050","url":null,"abstract":"<p><p>The search for effective therapeutics to combat COVID-19 has led to the exploration of the biological activity of numerous compounds. In this study, hydrazones derived from oseltamivir intermediate, methyl 5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylate have been investigated for their potential as drug candidates against the COVID-19 virus using computational methods, including density functional theory (DFT) studies, molecular docking, and absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis. The DFT studies provide information on the electronic properties of the compounds while the molecular docking results using AutoDock reported the binding energies between the main protease of COVID-19 and the compounds. The DFT results revealed that the energy gap of the compounds ranged from 4.32 to 5.82 eV while compound HC had the highest energy gap (5.82 eV) and chemical potential (2.90 eV). The electrophilicity index values of the 11 compounds ranged from 2.49 to 3.86, thus they were classified as strong electrophiles. The molecular electrostatic potential (MESP) revealed electron-rich and electron-deficient regions of the compounds. The docking results reveal that all the compounds had better docking scores than remdesivir and chloroquine, frontline drugs employed in combating COVID-19, with HC having the best docking score of -6.5. The results were visualized using Discovery studio, which revealed hydrogen bonding, pi-alkyl interaction, alkyl interaction, salt bridge interaction, halogen interaction as being responsible for the docking scores. The drug-likeness results showed that the compounds qualify as oral drug candidates as none of them violated Vebers and Lipinski's rule. Thus, they could serve as potential inhibitors of COVID-19.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"17 ","pages":"11779322231182050"},"PeriodicalIF":5.8,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/74/75/10.1177_11779322231182050.PMC10291222.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9724400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 Epidemic Forecast in Brazil.","authors":"Oleg Gaidai, Yihan Xing","doi":"10.1177/11779322231161939","DOIUrl":"10.1177/11779322231161939","url":null,"abstract":"<p><p>This study advocates a novel spatio-temporal method for accurate prediction of COVID-19 epidemic occurrence probability at any time in any Brazil state of interest, and raw clinical observational data have been used. This article describes a novel bio-system reliability approach, particularly suitable for multi-regional environmental and health systems, observed over a sufficient time period, resulting in robust long-term forecast of the virus outbreak probability. COVID-19 daily numbers of recorded patients in all affected Brazil states were taken into account. This work aimed to benchmark novel state-of-the-art methods, making it possible to analyse dynamically observed patient numbers while taking into account relevant regional mapping. Advocated approach may help to monitor and predict possible future epidemic outbreaks within a large variety of multi-regional biological systems. Suggested methodology may be used in various modern public health applications, efficiently using their clinical survey data.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"17 ","pages":"11779322231161939"},"PeriodicalIF":2.3,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c3/9b/10.1177_11779322231161939.PMC10090958.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9373160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacophore-Aided Virtual Screening and Molecular Dynamics Simulation Identifies TrkB Agonists for Treatment of <i>CDKL5</i>-Deficiency Disorders.","authors":"Ibitayo Abigail Ademuwagun, Gbolahan Oladipupo Oduselu, Solomon Oladapo Rotimi, Ezekiel Adebiyi","doi":"10.1177/11779322231158254","DOIUrl":"10.1177/11779322231158254","url":null,"abstract":"<p><p>Therapeutic intervention in cyclin-dependent kinase-like 5 (CDKL5) deficiency disorders (CDDs) has remained a concern over the years. Recent advances into the mechanistic interplay of signalling pathways has revealed the role of deficient tropomyosin receptor kinase B (TrkB)/phospholipase C γ1 signalling cascade in CDD. Novel findings showed that in vivo administration of a TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), resulted in a remarkable reversal in the molecular pathologic mechanisms underlying CDD. Owing to this discovery, this study aimed to identify more potent TrkB agonists than 7,8-DHF that could serve as alternatives or combinatorial drugs towards effective management of CDD. Using pharmacophore modelling and multiple database screening, we identified 691 compounds with identical pharmacophore features with 7,8-DHF. Virtual screening of these ligands resulted in identification of at least 6 compounds with better binding affinities than 7,8-DHF. The in silico pharmacokinetic and ADMET studies of the compounds also indicated better drug-like qualities than those of 7,8-DHF. Postdocking analyses and molecular dynamics simulations of the best hits, 6-hydroxy-10-(2-oxo-1-azatricyclo[7.3.1.05,13]trideca-3,5(13),6,8-tetraen-3-yl)-8-oxa-13,14,16-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1,3,6,9,11,15-hexaen-5-one (PubChem: 91637738) and 6-hydroxy-10-(8-methyl-2-oxo-1H-quinolin-3-yl)-8-oxa-13,14,16-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1,3,6,9,11,15-hexaen-5-one (PubChem ID: 91641310), revealed unique ligand interactions, validating the docking findings. We hereby recommend experimental validation of the best hits in CDKL5 knock out models before consideration as drugs in CDD management.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"17 ","pages":"11779322231158254"},"PeriodicalIF":2.3,"publicationDate":"2023-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/c5/10.1177_11779322231158254.PMC9989394.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9437716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Insight Into Mechanisms of Hepatic Encephalopathy: An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets.","authors":"Ali Sepehrinezhad, Ali Shahbazi, Sajad Sahab Negah, Fin Stolze Larsen","doi":"10.1177/11779322231155068","DOIUrl":"10.1177/11779322231155068","url":null,"abstract":"<p><p>Hepatic encephalopathy (HE) is a set of complex neurological complications that arise from advanced liver disease. The precise molecular and cellular mechanism of HE is not fully understood. Differentially expressed genes (DEGs) from microarray technologies are powerful approaches to obtain new insight into the pathophysiology of HE. We analyzed microarray data sets of cirrhotic patients with HE from Gene Expression Omnibus to identify DEGs in postmortem cerebral tissues. Consequently, we uploaded significant DEGs into the STRING to specify protein-protein interactions. Cytoscape was used to reconstruct the genetic network and identify hub genes. Target genes were uploaded to different databases to perform comprehensive enrichment analysis and repurpose new therapeutic options for HE. A total of 457 DEGs were identified in 2 data sets totally from 12 cirrhotic patients with HE compared with 12 healthy subjects. We found that 274 genes were upregulated and 183 genes were downregulated. Network analyses on significant DEGs indicated 12 hub genes associated with HE. Enrichment analysis identified fatty acid beta-oxidation, cerebral organic acidurias, and regulation of actin cytoskeleton as main involved pathways associated with upregulated genes; serotonin receptor 2 and ELK-SRF/GATA4 signaling, GPCRs, class A rhodopsin-like, and p38 MAPK signaling pathway were related to downregulated genes. Finally, we predicted 39 probable effective drugs/agents for HE. This study not only confirms main important involved mechanisms of HE but also reveals some yet unknown activated molecular and cellular pathways in human HE. In addition, new targets were identified that could be of value in the future study of HE.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"17 ","pages":"11779322231155068"},"PeriodicalIF":2.3,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3f/20/10.1177_11779322231155068.PMC9940182.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10764638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In silico</i> Structure Prediction, Molecular Docking, and Dynamic Simulation of <i>Plasmodium falciparum</i> AP2-I Transcription Factor.","authors":"David O Oladejo, Gbolahan O Duselu, Titilope M Dokunmu, Itunuoluwa Isewon, Jelili Oyelade, Esther Okafor, Emeka Ej Iweala, Ezekiel Adebiyi","doi":"10.1177/11779322221149616","DOIUrl":"10.1177/11779322221149616","url":null,"abstract":"<p><p><i>Plasmodium falciparum</i> Apicomplexan Apetala 2 Invasion (<i>Pf</i>AP2-I) transcription factor (TF) is a protein that regulates the expression of a subset of gene families involved in <i>P. falciparum</i> red blood cell (RBC) invasion. Inhibiting <i>Pf</i>AP2-I TF with small molecules represents a potential new antimalarial therapeutic target to combat drug resistance, which this study aims to achieve. The 3D model structure of <i>Pf</i>AP2-I was predicted <i>ab initio</i> using ROBETTA prediction tool and was validated using Save server 6.0 and MolProbity. Computed Atlas of Surface Topography of proteins (CASTp) 3.0 was used to predict the active sites of the <i>Pf</i>AP2-I modeled structure. Pharmacophore modeling of the control ligand and <i>Pf</i>AP2-I modeled structure was carried out using the Pharmit server to obtain several compounds used for molecular docking analysis. Molecular docking and postdocking studies were conducted using AutoDock vina and Discovery studio. The designed ligands' toxicity predictions and <i>in silico</i> drug-likeness were performed using the SwissADME predictor and OSIRIS Property Explorer. The modeled protein structure from the ROBETTA showed a validation result of 96.827 for ERRAT, 90.2% of the amino acid residues in the most favored region for the Ramachandran plot, and MolProbity score of 1.30 in the 98th percentile. Five (5) best hit compounds from molecular docking analysis were selected based on their binding affinity (between -8.9 and -11.7 Kcal/mol) to the active site of <i>Pf</i>AP2-I and were considered for postdocking studies. For the absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties, compound MCULE-7146940834 had the highest drug score (0.63) and drug-likeness (6.76). MCULE-7146940834 maintained a stable conformation within the flexible protein's active site during simulation. The good, estimated binding energies, drug-likeness, drug score, and molecular dynamics simulation interaction observed for MCULE-7146940834 against <i>Pf</i>AP2-I show that MCULE-7146940834 can be considered a lead candidate for <i>Pf</i>AP2-I inhibition. Experimental validations should be carried out to ascertain the efficacy of these predicted best hit compounds.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"17 ","pages":"11779322221149616"},"PeriodicalIF":5.8,"publicationDate":"2023-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/14/a7/10.1177_11779322221149616.PMC9871981.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10625593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel c.100C > G Mutation in the <i>FST</i> Gene and Its Relation With the Reproductive Traits of Awassi Ewes.","authors":"Tahreer M Al-Thuwaini,&nbsp;Wefak J Albazi,&nbsp;Mohammed Baqur S Al-Shuhaib,&nbsp;Layth H Merzah,&nbsp;Rihab G Mohammed,&nbsp;Fadhil A Rhadi,&nbsp;Ali B Abd Al-Hadi,&nbsp;Ahmed H Alkhammas","doi":"10.1177/11779322231170988","DOIUrl":"https://doi.org/10.1177/11779322231170988","url":null,"abstract":"<p><p>Reproductive traits are affected by many factors, including ovarian function, hormones, and genetics. Genetic polymorphisms of candidate genes are associated with reproductive traits. Several candidate genes are associated with economic traits, including the follistatin (<i>FST</i>) gene. Thus, this study aimed to evaluate whether the genetic variations in the <i>FST</i> gene are associated with the reproductive traits in Awassi ewes. The genomic DNA was extracted from 109 twin ewes and 123 single-progeny ewes. Therefore, 4 sequence fragments from the <i>FST</i> gene were amplified using polymerase chain reaction (PCR) (exon 2/240, exon 3/268, exon 4/254, and exon 5/266 bp, respectively). For a 254 bp amplicon, 3 genotypes were identified: CC, CG, and GG. Sequencing revealed a novel mutation in CG genotypes c.100C > G. The statistical analysis of c.100C > G showed an association with reproductive characteristics. Ewes carrying the c.100C > G had significantly (<i>P</i> ⩽ .01) lower litter sizes, twinning rates, lambing rates, and more days to lambing compared with CG and CC genotypes. Logistic regression analysis confirmed that the c.100C > G single-nucleotide polymorphism (SNP) is responsible for decreasing litter size. According to these results, the variant c.100C > G negatively affects the traits of interest and is associated with lower reproductive traits in Awassi sheep. As a result of this study, ewes carrying the c.100C > G SNP have lower litter size and are less prolific.</p>","PeriodicalId":9065,"journal":{"name":"Bioinformatics and Biology Insights","volume":"17 ","pages":"11779322231170988"},"PeriodicalIF":5.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/0a/10.1177_11779322231170988.PMC10159244.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9433084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}