In silico pharmacology最新文献

{"title":"Deciphering phosphodiesterase-5 inhibitors from <i>Aframemum melegueta</i>: computational models against erectile dysfunction.","authors":"Damilola Alex Omoboyowa","doi":"10.1007/s40203-024-00284-3","DOIUrl":"https://doi.org/10.1007/s40203-024-00284-3","url":null,"abstract":"<p><p>Insufficient and inability to maintain erection in male for satisfactory sexual performance remains global challenge among couples. The identification of phosphodiesterase-5 (PDE-5) antagonist in the pathogenesis of erectile dysfunction has improved the search for therapeutic agents for the management of this sexual dysfunction. Here in, bioactive compounds from <i>Aframomum melegueta</i> were virtually screened against PDE-5 using Schrodinger suite 2017-1 as computational tool. The lead compound was further validated in comparison with sildenafil by performing 100 ns molecular dynamics (MD) simulation using Desmond. Among 109 bioactive compounds screened, nine (9) molecules were predicted as potent inhibitors of PDE-5 with binding affinities comparable to the co-crystalized ligand (sildenafil). 1,7-bis(3,4-dihyroxy-5-methoxyphenyl)heptane-3,5-diyldiacetate was observed to have the best docking score (-11.522 kcal/mol) among the hit compounds which is very close to the co-crystalized ligand (-11.872 kcal/mol). Validation using pharmacophore hypothesis and QSAR modeling further confirmed the prediction of the hit compounds with fitness score ranging from 0.754 to 2.605 and predicted pIC50 of 3.835 to 7.976 µM. All the hit compounds obeyed Lipinski's rule of five and within the reference range of the pharmacokinetics parameters. The MD simulation result predicted the stability of 1,7-bis(3,4-dihydroxy-5-methoxyphenyl)heptane-3,5-diyldiacetate-PDE-5 complex comparable to the sildenafil-PDE-5 complex. The outcome of this study predicted nine molecules from <i>A. melegueta</i> as potent PDE-5 antagonists which required isolation and experimental validation for the management of erectile dysfunction.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00284-3.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"101"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142636162","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":"Development of a Multiple-Epitope-Based Vaccine for Hepatitis C Virus Genotypes 1a and 1b: an in-silico reverse vaccinology approach.","authors":"Enakshi Das, Mahesh Samantaray, Kajal Abrol, Jayarani Basumatari, Shilpa Sri Pushan, Amutha Ramaswamy","doi":"10.1007/s40203-024-00275-4","DOIUrl":"https://doi.org/10.1007/s40203-024-00275-4","url":null,"abstract":"<p><p>The Hepatitis C virus (HCV) is a blood-transmitted virus responsible for persistent inflammation, presenting a substantial worldwide health challenge. HCV, characterized by a positive-stranded ribonucleic acid genome, possesses an intricate genetic makeup encoding both structural and non-structural proteins, crucial for sustaining its life cycle. The Direct Acting Antivirals have revolutionized the treatment landscape of HCV promoting higher Sustained Virological Response rates. Despite significant advancements in treatment, no vaccines are currently available against HCV. The development of effective HCV vaccines becomes challenging as the genetic diversity of HCV virus and its complex nature of the immune response required for protection. In this work, the immunoinformatics methods were utilized to develop a multiple-epitope-based vaccine towards an effective treatment against the viral HCV polyprotein. The vaccine was constructed by T-cell epitopes extracted from the viral polyprotein of HCV genotypes 1a and 1b. The vaccine was highly antigenic, non-toxic, and non-allergenic. Effective binding of the designed vaccine construct was studied by forming complexes with the human immune Toll-Like Receptors; TLR3 and TLR8. The MD simulation of these receptor-vaccine complexes were performed for 50ns and the immunological simulation of modeled vaccine in presence of receptors for 365 days timeline validated the stability of the constructed vaccine. The in-silico vaccine construct developed from this work might be beneficial as prophylactic measures against the HCV variants, if explored further in in vivo and in vitro methods. Consequently, this research outcome is presumed to have implications in the development of safer and more efficient vaccines for lethal diseases.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00275-4.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"100"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635145","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":"Scaffold transforming and in-silico design of potential androgen receptor antagonists in prostate cancer therapy.","authors":"Ajay Kumar Gupta, Piyush Ghode, Sanmati Kumar Jain","doi":"10.1007/s40203-024-00274-5","DOIUrl":"https://doi.org/10.1007/s40203-024-00274-5","url":null,"abstract":"<p><p>Androgens like testosterone and dihydrotestosterone are essential for the growth and development of the prostate gland. Androgenic receptors are overexpressed, which promotes the progression of prostate cancer; therefore, androgenic receptors are a key target in the therapy of prostate cancer. Enzalutamide is used to treat prostate cancer; however, it also causes toxicities such as cardiovascular toxicity, acute myocarditis, hypertension, and seizures. The objective of this research was to create novel and safer analogues of enzalutamide, followed by the prediction of the pharmacokinetic and toxicity characteristics of these enzalutamide analogues. Molecular docking studies of analogues were also done to guess how ligands will work biologically in treating prostate cancer. A total of 195 analogues were generated, and among them, 23 bioisosteres were selected for further pharmacokinetic, toxicological screening and docking studies. The predicted physical-chemical, medicinal, and ADMET characteristics of the designed bioisosteres were optimal to good compared to enzalutamide. Additionally, the drug likeness and drug score of analogues were superior to enzalutamide. According to docking studies of analogues, EZ12, EZ8, and EZ10 formed hydrogen bonds of SER778 with replaceable amide groups in enzalutamide molecules. SER778 residue may be responsible for antagonistic activity towards androgen receptors. Based on the results of the ADMET, drug likeness, drug score, and docking study of designed enzalutamide analogues, the ligands EZ12, EZ8, and EZ10 could be used to find more possible antiandrogen drugs that could be used to treat prostate cancer.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"99"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635180","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":"Effects of some anti-ulcer and anti-inflammatory natural products on cyclooxygenase and lipoxygenase enzymes: insights from in silico analysis.","authors":"Jonathan A Metuge, Jude Y Betow, Boris D Bekono, Mathieu Jules Mbenga Tjegbe, Roland N Ndip, Fidele Ntie-Kang","doi":"10.1007/s40203-024-00269-2","DOIUrl":"10.1007/s40203-024-00269-2","url":null,"abstract":"<p><p>Gastric and duodenal ulcers are increasingly becoming global health burdens. The side effects of conventional treatments such as non-steroid anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), antibiotics, and cytoprotective agents have necessitated the search for new medications. Plants are a rich source of active metabolites and herbal medicines have been used in the treatment of ulcers and cancers. In this study, we used in silico methods like molecular docking and MM-GBSA calculations to evaluate the effects of some anti-ulcer and anti-inflammatory phytochemicals on some key enzymes, cyclooxygenase (COX), and lipoxygenase (LOX), which are implicated in the protection and destruction of the gastric mucosa. The phytochemicals were retrieved from the literature and docked toward the binding sites of the three enzymes (COX-1, COX-2, and 5-LOX). Five compounds, rhamnetin, kaempferol, rutin, rosmarinic acid, and chlorogenic acid were observed to putatively bind to cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) but not to cyclooxygenase 1 (COX-1). The interaction mechanisms between these phytochemicals and the target proteins are discussed. The compounds' drug metabolism, pharmacokinetics, and toxicity have been evaluated to assess their suitability as potential next-generation anti-ulcer and anti-inflammatory drugs.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00269-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"97"},"PeriodicalIF":0.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575205","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":"Molecular docking and network pharmacology study on active compounds of <i>Cyprus rotundus</i> for the treatment of diabetes mellitus.","authors":"Vishakha Desai, Mohammad Ziyad Shaikhsurab, Nimmy Varghese, Harsha Ashtekar","doi":"10.1007/s40203-024-00273-6","DOIUrl":"10.1007/s40203-024-00273-6","url":null,"abstract":"<p><strong>Background: </strong>Diabetes Mellitus (DM) is a complex metabolic disorder with increasing global prevalence, necessitating the exploration of novel therapeutic strategies. <i>Cyprus rotundus</i>, a medicinal plant with a long history of traditional use, has shown promising potential in managing DM.</p><p><strong>Aim of the study: </strong>This study aims to elucidate the mechanism of action of active components of <i>C. rotundus</i> in managing DM using a combination of network pharmacology and molecular docking approaches.</p><p><strong>Materials and methods: </strong>The active compounds of <i>C. rotundus</i> were identified through IMPPAT and CHEBI database mining. Subsequently, compound-target are taken from swiss target prediction and SEA. Collection of DM-related targets is done through DisGeNET and TTD database. After identifying both the targets, common targets were evaluated through venny 2.1.0. by constructing venn diagram. To elucidate the potential targets of these compounds, a protein-protein interaction network was constructed by utilizing STRING database. Through network analysis, we identified key targets and pathways involved in the pathogenesis of DM and targeted by the active components of <i>C. rotundus</i>. Furthermore, molecular docking was performed to explore the binding affinity and interactions between the active compounds and their target proteins.</p><p><strong>Results: </strong>This, reveal that the 12 active components of <i>C. rotundus</i> exert their therapeutic effects on DM through multiple mechanisms, there are 141 common target genes between <i>C. rotundus</i> and DM. Enrichment of the KEGG pathway mainly involves in the AGE-RAGE signaling pathway in diabetic complications, Type II DM pathway. Top 10 genes were regulated by <i>C. rotundus</i> in DM, including MMP9, PTGS2, CASP3, CD4, EGFR, STAT3, PPARG, AKT1, NFKB1 and MAPK3. Molecular docking analysis further validates the strong binding affinity between the active compounds and their target proteins, providing insights into their mode of action at the molecular level.</p><p><strong>Conclusions: </strong>This study provides a systematic understanding of the mechanism of action of <i>C. rotundus</i> in managing DM, offering a basis for further experimental validation and drug development.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"98"},"PeriodicalIF":0.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575633","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":"Molecular mechanisms of sulforaphane in Alzheimer's disease: insights from an in-silico study.","authors":"Giang Huong Vu, Hai Duc Nguyen","doi":"10.1007/s40203-024-00267-4","DOIUrl":"10.1007/s40203-024-00267-4","url":null,"abstract":"<p><p>This study was to identify the molecular pathways that may explain sulforaphane's Alzheimer's disease (AD) benefits using multiple advanced in silico approaches. We found that sulforaphane regulates 45 targets, including TNF, INS, and BCL2. Therefore, it may help treat AD by reducing neuroinflammation, insulin resistance, and apoptosis. The important relationships were co-expression and pathways. 45 targets were linked to the midbrain, metabolite interconversion enzymes, 14q23.3 and 1q31.1 chromosomes, and modified residues. \"Amyloid precursor protein catabolic process\", \"regulation of apoptotic signaling pathway\", and \"positive regulation of nitric oxide biosynthetic process\" were the main pathways, while NFKB1, SP1, RELA, hsa-miR-17-5p, hsa-miR-16-5p, and hsa-miR-26b-5p were transcription factors and miRNAs implicated in sulforaphane In AD treatment, miRNA sponges, dexibuprofen, and sulforaphane may be effective. Furthermore, its unique physicochemical, pharmacokinetic, and biological qualities make sulforaphane an effective AD treatment, including efficient gastrointestinal absorption, drug-like properties, absence of CYP450 enzyme inhibition, not being a substrate for P-glycoprotein, ability to cross the blood-brain barrier, glutathione S-transferase substrate, immunostimulant effects, and antagonistic neurotransmitter effects. Sulforaphane is a promising compound for AD management. Further work is needed to elucidate its therapeutic effects based on our findings, including genes, miRNAs, molecular pathways, and transcription factors.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00267-4.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"96"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570811","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":"Glucosinolates and Indole-3-carbinol from <i>Brassica oleracea</i> L. as inhibitors of <i>E. coli</i> CdtB: insights from molecular docking, dynamics, DFT and in vitro assay.","authors":"Faria Tasnim, Md Eram Hosen, Md Enamul Haque, Ariful Islam, Mst Naharina Nuryay, Jannatul Mawya, Najnin Akter, Delara Yesmin, Md Mosabbir Hossain, Nilima Rahman, B M Mahmudul Hasan, Md Naimul Hassan, Md Mahmudul Islam, Md Khalekuzzaman","doi":"10.1007/s40203-024-00276-3","DOIUrl":"10.1007/s40203-024-00276-3","url":null,"abstract":"<p><p><i>Escherichia coli</i> (<i>E. coli</i>), a common human gut bacterium, is generally harmless but capable of causing infections and contributing to diseases like urinary tract infections, sepsis/meningitis, or diarrheal diseases. Notably, <i>E. coli</i> is implicated in developing gallbladder cancer (GBC) either through ascending infection from the gastrointestinal tract or via hematogenous spread. Certain <i>E. coli</i> strains are known to produce toxins, such as cytolethal distending toxins (CDTs), that directly contribute to the genetic mutations and cellular abnormalities observed in GBC. Broccoli (<i>Brassica oleracea</i>) is known for its health-promoting properties, including antimicrobial, antioxidant, and immunomodulatory effects, and is rich in essential compounds. Our study investigates the potential of the phytochemicals of <i>B. oleracea</i> to inhibit the CdtB (PDB ID: 2F1N) protein of <i>E. coli</i> which plays a significant role in the pathogenesis of GBC. By employing in silico molecular docking, Glucosinolates and Indole-3-carbinol emerged as promising inhibitors, demonstrating strong bonding affinities of -8.95 and - 8.5 Kcal/mol, respectively. The molecular dynamic simulation showed that both compounds maintained stable interaction with CdtB with minimal conformational changes observed in the protein-ligand complexes. Additionally, the ADMET analysis provided evidence for the drug-likeness properties of the lead compounds. Furthermore, the DFT (Density Functional Theory) revealed that Indole-3-carbinol is more chemically stable but less reactive than Glucosinolates, with HOMO-LUMO gaps of 5.14 eV and 4.50 eV, respectively. Finally, the in vitro antibacterial assessment confirmed the inhibitory effect of Glucosinolates and Indole-3-carbinol against <i>E. coli</i> through disc diffusion assay with the zone of inhibition 34.25 ± 0.541 and 28.67 ± 0.376 mm compared to the control ciprofloxacin. Our study provides crucial data for developing novel therapeutic agents targeting <i>E. coli</i>-associated GBC from the phytochemicals of <i>B. oleracea</i>.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00276-3.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"95"},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549778","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":"Protein-protein interaction network study of metallo-beta-lactamase-L1 present in <i>Stenotrophomonas maltophilia</i> and identification of potential drug targets.","authors":"K H Sreenithya, Shobana Sugumar","doi":"10.1007/s40203-024-00270-9","DOIUrl":"10.1007/s40203-024-00270-9","url":null,"abstract":"<p><p>Microorganisms are evolving to withstand the effect of antimicrobial agents and thereby pose a global threat known as antimicrobial resistance. Resistance towards multiple drugs due to various intrinsic as well environmental factors leads to an even more dangerous drug resistance property known as multi-drug resistance (MDR). WHO has recognized MDR bacteria as a top global threat as they complicate the treatment and augment mortality and morbidity risks. Gram-negative bacteria produce beta-lactamase enzymes that can hydrolyze beta-lactam antibiotics, impacting drug susceptibility. <i>Stenotrophomonas maltophilia</i>, an opportunistic pathogen, exemplifies MDR due to the production of two types of beta-lactamases. The metallo-beta-lactamase (MBL) L1 produced by the bacteria is a class B1 zinc-dependent MBL that is broadly substrate-specific and is a challenge to the currently available treatment options. This study constructs and analyzes a protein-protein interaction network of L1 beta-lactamase to comprehend its role in the MDR property of the bacteria. The network encompasses 51 proteins including L1 MBL (Smlt2667) and 382 interactions, revealing key players in MDR and potential drug targets. The network analysis aids the discernment of antimicrobial gene impact on cellular function, informing drug discovery strategies. This research addresses the emerging challenge of antibiotic resistance and identifies pathways for therapeutic intervention.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00270-9.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"94"},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549790","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 pan-genomic analysis based multi-epitope vaccine development by targeting <i>Stenotrophomonas maltophilia</i> using reverse vaccinology method: an in-silico approach.","authors":"Md Hasan Jafre Shovon, Md Imtiaz, Partha Biswas, Md Mohaimenul Islam Tareq, Md Nazmul Hasan Zilani, Md Nazmul Hasan","doi":"10.1007/s40203-024-00271-8","DOIUrl":"10.1007/s40203-024-00271-8","url":null,"abstract":"<p><p>Antibiotic resistance in bacteria leads to high mortality rates and healthcare costs, a significant concern for public health. A colonizer of the human respiratory system, <i>Stenotrophomonas maltophilia</i> is frequently associated with hospital-acquired infections in individuals with cystic fibrosis, cancer, and other chronic illnesses. The importance of this study is underscored by its capacity to meet the critical demand for effective preventive strategies against this pathogen, particularly among susceptible groups of cystic fibrosis and those undergoing cancer treatment. In this study, we engineered a multi-epitope vaccine targeting <i>S. maltophilia</i> through genomic analysis, reverse vaccination strategies, and immunoinformatic techniques by examining a total of 81 complete genomes of S. maltophilia strains. Our investigation revealed 1945 core protein-coding genes alongside their corresponding proteomic sequences, with 191 of these genes predicted to exhibit virulence characteristics. Out of the filtered proteins, three best antigenic proteins were selected for epitope prediction while seven epitopes each from CTL, HTL, and B cell were chosen for vaccine development. The vaccine was refined and validated, showing highly antigenic and desirable physicochemical features. Molecular docking assessments revealed stable binding with TLR-4. Molecular dynamic simulation demonstrated stable dynamics with minor alterations. The originality of this investigation is rooted in the thorough techniques aimed at designing a vaccine that directly targets <i>S. maltophilia</i>, a microorganism of considerable clinical relevance that currently lacks an available vaccine. This study not only responds to a pressing public health crisis but also lays the groundwork for subsequent research endeavors focused on the prevention of <i>S. maltophilia</i> outbreaks. Further evidence from studies in mice models is needed to confirm immune protection against <i>S. maltophilia</i>.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"93"},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515310","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":"First report on exploration of structural features of natural compounds (NPACT database) for anti-breast cancer activity (MCF-7): QSAR-based virtual screening, molecular docking, ADMET, MD simulation, and DFT studies.","authors":"Lomash Banjare, Anjali Murmu, Nilesh Kumar Pandey, Balaji Wamanrao Matore, Purusottam Banjare, Arijit Bhattacharya, Shovanlal Gayen, Jagadish Singh, Partha Pratim Roy","doi":"10.1007/s40203-024-00266-5","DOIUrl":"10.1007/s40203-024-00266-5","url":null,"abstract":"<p><p>Due to the high toxicity, poor efficacy and resistance associated with current anti-breast cancer drugs, there's growing interest in natural products (NPs) for their potential anti-cancer properties. Computational modelling of NPs to identify key structural features can aid in developing novel natural inhibitors. In this study, we developed statistically significant QSAR models based on NPs from the NPACT database, which have shown potential anticancer activity against the MCF-7 cancer cell lines. All the developed QSAR models were statistically robust, meeting both internal (<i>R</i> ^<i>2</i>  = 0.666-0.669, <i>R</i> ^<i>2</i> _<i>adj</i>  = 0.657-0.660, <i>Q</i> ^<i>2</i> _<i>Loo</i>  = 0.636-0.638) and external (<i>Q</i> ^<i>2</i> <i>F</i> _<i>n</i>  = 0.686-0.714, <i>CCC</i> _<i>ext</i> = 0.830-0.847) validation criteria. Consequently, they were utilized to virtually screen a series of NPs from the COCONUT database in the search for novel natural inhibitors. Molecular docking studies were conducted on the identified compounds against the human HER2 protein (PDB ID: 3PP0), which is a crucial target in breast cancer. Molecular docking analysis demonstrated that compounds 4608 and 2710 achieved the highest docking scores, with CDOCKER interaction energies of -72.67 kcal/mol and - 72.63 kcal/mol respectively. Compounds 4608 and 2710 were identified as the most promising candidates upon performing triplicate 100 ns MD simulation study using the CHARMM36 force field. DFT studies was performed to evaluate their stability and reactivity as potential drug molecules. This research contributes to the development of new natural inhibitors for breast cancer.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00266-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"92"},"PeriodicalIF":0.0,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484158","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}