In silico pharmacology最新文献

{"title":"Network pharmacology and in silico approach to study the mechanism of quercetin against breast cancer.","authors":"Tejveer Singh, Mahi Rastogi, Kulbhushan Thakur","doi":"10.1007/s40203-025-00306-8","DOIUrl":"10.1007/s40203-025-00306-8","url":null,"abstract":"<p><p>Breast cancer is a significant health concern among females with an estimated 2.3 million cases reported worldwide in 2022. Traditional treatment methods have now developed resistance and various adverse effects, highlighting an urgent need for attention. Therefore, it is advisable to substitute these conventional therapies with innovative medications. Quercetin is a flavonoid, commonly found in various vegetables and fruits and have been shown to possess anti-cancer properties. Network pharmacology is a comprehensive approach that has significantly assisted in investigating the potential of quercetin as a therapeutic option for breast cancer. The first step includes target fishing for quercetin-targeted genes in breast cancer through various online available databases. All intersecting genes were analysed for the phenotypic- genotypic correlation via online VarElect analysis tool. Using the result from the result the GO enrichment and pathway enrichment analysis was done on 52 common genes; followed by PPI network construction and based on topological parameters top 8 genes were filtered. Based on theVenny2.1 and then GEPIA and HPA analysis the key target were identifies as ABCC1, ABCC4, AKT1, ABCB1, CYP1B1, CYP19A1, ABCB4 and ABCG2. Further, Molecular docking was done to investigate the possible interaction of the identified gene with quercetin. Our finding shows quercetin is the potential natural drug that can treat breast cancer effectively. Quercetin interacts with ABCC1, ABCC4, AKT1, ABCB1, CYP1B1, CYP19A1, ABCB4, and ABCG2 at cellular as well as molecular level. The ADMET analysis suggests the bioavaibility of quercetin is around 0.55. Suggesting that quercetin satisfies drug-likeness rules but may face challenges like low bioavailability, which can be enhanced through structural modifications or formulations (e.g., nanoparticles). The molecular docking result assures the interaction of quercetin with the ABCC1, ABCC4, AKT1, ABCB1, CYP1B1, CYP19A1, ABCB4, and ABCG2 with the binding affinity of - 7.2, - 10.1, - 10.4, - 8.0, - 8.2, - 8.2, - 9.0 and - 8.9 respectively. These results suggest quercetin has a stable interaction with the ABCC4 gene. Considering this interaction the quercetin molecules can rescue the cellular condition by inducing apoptosis, inhibiting proliferation, and suppressing metastasis. Quercetin, a natural compound found in fruits and vegetables, has been found to have significant therapeutic roles in treating breast cancer. It inhibits cell cycle arrest, promotes apoptosis, and reduces blood vessel formation. It also reverses drug resistance and has antioxidant and anti-inflammatory properties. This study concludes that the therapeutic influence of quercetin plays a significant role in treating breast cancer and aids in the advancement of the clinical application of quercetin in future studies.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384615","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":"Multi-scale computational modeling to identify novel chemical scaffolds as trehalose-6-phosphate phosphatase inhibitors to combat <i>Burkholderia pseudomallei</i>.","authors":"Sara Noor, Mohammad Abdullah Aljasir, Maryam Bashir, Kalsoom Khan, Sajjad Ahmad, Syed Ainul Abideen, Saifullah Khan, Farhan Siddique, Hamza Ahmad, Khudija Ghani, Madiha Iqbal, Muhammad Irfan, Abbas Khan, Dong-Qing Wei","doi":"10.1007/s40203-025-00309-5","DOIUrl":"10.1007/s40203-025-00309-5","url":null,"abstract":"<p><p><i>Burkholderia pseudomallei</i> causes melioidosis, a deadly infection having high fatality rates (20-50%) and antibiotic resistance, however, there's no effective drug or vaccine available. Trehalose is a vital sugar for <i>B. pseudomallei</i> which influences the pathogen resilience and pathogenicity. This proposed computational strategy focuses on developing novel drugs against Trehalose-6-phosphate Phosphatase (TPP) to combat infections. This study found three novel drugs from Asinex, Zinc, Chembridge, and Drugbank databases through a comprehensive structure-based virtual screening. The process screened the top three compounds: BDG_34042863, BDF_33738612, and DB00139 along with control (2-methyl-6-phenoxytetrahydro-2 H-pyran-3,4,5-triol) with a binding energy score of -8.8 kcal/mol, -8.4 kcal/mol, and - 7.7 kcal/mol, -6.4 kcal/mol respectively. In a molecular dynamics simulation, the Ligand-protein complexes demonstrated substantial non-covalent interactions as well as a stable docked intermolecular binding conformation. Throughout the MDS (molecular dynamic simulation) period, the studied compounds showed stable consistent interactions; there were no noticeable changes in the interactions or binding mode. The BDG_34042863, BDF_33738612, and DB00139 had a mean deviation of 4.04, 7.18, and 7.10 measured in Å, respectively. In addition, the simulation trajectories of complexes underwent MM/GBSA analysis, which revealed binding affinity scores of -33.39, -41.1, -49.16, and - 41.29 measured in kcal/mol for the control, BDG_34042863, BDF_33738612, and DB00139, respectively. According to DFT Analysis, BDF_33738612 showed the smallest energy gap (0.46 eV), indicating high reactivity, while DB00139 showed the largest energy gap (5.66 eV), illustrating good kinetic stability compared to the control. The compounds exhibit notable differences in reactivity and stability levels as their HOMO-1 to LUMO + 1 and HOMO-2 to LUMO + 2 orbitals have greater energy gaps, ranging from 5.06 eV to 6.69 eV and 5.66 eV to 7.09 eV, respectively. The compounds also had favorable pharmacokinetic characteristics and were categorized as druglike. Among the selected compounds, BDF_33738612 demonstrated the most promising findings followed by BDG_34042863 and DB00139. The compounds may be employed in an experimental study to examine their anti-TPP activity against <i>B. pseudomallei</i>.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00309-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124295","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":"Allosteric activation of AMPK ADaM's site by structural analogs of Epigallocatechin and Galegine: computational molecular modeling investigation.","authors":"Mohnad Abdalla, Abdeen Tunde Ogunlana, Modinat Wuraola Akinboade, Ridwan Olajire Muraina, Oyindamola Anthonia Adeosun, Onyekachi Juliet Okpasuo, Olamide Tosin Olaoba, Abdulaziz Alouffi, Aqel Albutti, Zeyad Kurdee, Nouf Omar AlAfaleq, Ajibola Hannah Fatoberu, Temitope Isaac Adelus","doi":"10.1007/s40203-025-00311-x","DOIUrl":"10.1007/s40203-025-00311-x","url":null,"abstract":"<p><p>5'-Adenosine Monophosphate Protein Kinase (AMPK) is a central protein involved in cellular energy homeostasis, turning on catabolic pathways when the energy level is depleted and inhibiting anabolic pathways utilizing ATP. AMPK is implicated in several diseases including but not limited to diabetes, cancer, and cardiovascular diseases. Regulation of AMPK is cogent for restoring cellular energy levels which mediates the pathways leading to these diseases. Allosteric activation of AMPK via a novel ADaM site is intended for study in this case. In the search for AMPK activators, this study engaged a database for a virtual screening campaign through the ZINC15 database involving pharmacophoric modeling of two reported natural bioactive AMPK activators- Galegine and Epigallocatechin. Generated pharmacophores were targeted against the AMPK-ADaM site by employing various tools within the structure-based drug discovery process among which include consensus molecular docking, physicochemical profiling, ADMET, and molecular dynamics simulation. Advanced methods such as molecular mechanics (MM/GBSA) and quantitative structure-activity relationship (QSAR) were also performed. This investigation revealed promising pharmacophores that show better interactions and pharmacokinetic properties compared to the standards. This study proposes further development of these pharmacophores into potential drugs with better efficacies that could enhance the activation of the AMPK-ADaM site in ameliorating the aforementioned diseases.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00311-x.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081875","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":"From phytomedicine to conventional drug research, to look for new drug molecule against monkey pox virus; a molecular docking, virtual screening and ADME analysis.","authors":"Pritam Goswami, Emmanuel Gabriel Fakola, Sayak Ghosh, Shubhamoy Ghosh, Satadal Das","doi":"10.1007/s40203-025-00310-y","DOIUrl":"10.1007/s40203-025-00310-y","url":null,"abstract":"<p><p>Globally, traditional and complementary therapies (such as homeopathy, phytotherapy and herbal medications) are becoming increasingly prevalent alongside modern medical care. The therapeutic substances used in homeopathy and other traditional complementary medicine disciplines are derived from these traditional applications. Numerous notable clinical and preclinical studies have shown their impact during COVID-19. This study aims to investigate the potential antiviral effects of medicinal alkaloids against the monkeypox virus in the current scenario. The structures of 47 known phytochemicals of commonly used medicines in CAM were obtained from PubChem in SDF format, minimized, and then docked against the 3D crystal structure of monkeypox virus methyltransferase VP39 (PDB: 8B07). The results were analyzed, and compounds with significant docking scores were further evaluated. The docking results showed that six compounds-Sarsaponin, Luteolin, Quercetin, Apigenin, and Ducimarine-had better docking scores than Tecovirimat, a standard drug used in managing monkeypox. Additionally, most compounds exhibited better docking scores than Cidofovir, another drug used against monkeypox. Interaction analysis revealed that hydrogen bonding, pi-pi T-shaped, and pi-alkyl interactions were responsible for the observed docking scores. Key amino acid residues involved in the interaction between the compounds and monkeypox virus methyltransferase VP39 included GLY 96, LEU 159, PHE 115, VAL 139, VAL 116, GLY 68, ARG 140, ILE 94, ASN 156, and ARG 156. Five phytochemicals-Luteolin, Quercetin, Apigenin, Sarsaponin, and Ducimarine-show strong potential as monkeypox virus methyltransferase inhibitors. Apigenin and Ducimarine are particularly promising due to their favorable profiles, including no PAINS alerts and good drug-like properties. Sarsaponin, while highly permeable, has high lipophilicity, which may limit its use. Luteolin and Quercetin also show potential but require further investigation due to PAINS alerts.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082096","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 <i>Aframomum melegueta</i> compounds as ERK5 inhibitor related to breast cancer via molecular docking and dynamic simulation.","authors":"Paul Olamide Ottu, Olorunfemi Oyewole Babalola, Cecilia Oluwamodupe, Ayodeji Folasade Oluwatobiloba, Idayat Oyinkansola Kehinde, Olufemi Adebisi Akinola, Sulyman Olalekan Ibrahim, Olusola Olalekan Elekofehinti","doi":"10.1007/s40203-025-00304-w","DOIUrl":"10.1007/s40203-025-00304-w","url":null,"abstract":"<p><p>Breast cancer remains a global health challenge, with rising cases predicted in the coming decades. The complexity of breast cancer treatment arises from its complex nature, often involving multiple therapeutic strategies. One promising approach is targeting the ERK5 pathway, a key regulator in cancer cell proliferation and survival. In this study, we explored the anticancer potential of bioactive compounds from <i>Aframomum melegueta</i>, a plant traditionally used in West African medicine. The 3D structure of ERK5 (PDB ID: 4B99) was prepared and optimized using the Schrödinger Protein Preparation Wizard. Six phytochemicals from <i>Aframomum melegueta</i> were screened for their binding affinities to ERK5 using GlideXP docking. Dihydrogingerenone A,1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxyphenyl) heptane-3,5-diyldiacetate and Dihydrogingerenone C emerged as the lead compound, demonstrating a high docking score of -  9.659 kcal/mol, -  9.383 kcal/mol, and - 8.264 kcal/mol compared to standard anticancer drugs like Docetaxel (- 4.175 kcal/mol) and Temozolomide (- 5.443 kcal/mol). Post-docking analyses using MM-GBSA free energy calculations confirmed the compound's high binding stability, with van der Waals interactions and hydrogen bonding at critical residues such as Met140 playing a significant role. Pharmacokinetic profiling using ADME analysis showed that our compounds exhibited favorable drug-likeness properties, adhering to Lipinski's Rule of Five without violations. QSAR modeling and molecular dynamics (MD) simulations further validated its pharmacological potential. These findings suggest that <i>Aframomum melegueta</i> contains bioactive compounds with strong potential as ERK5 inhibitors, offering a novel approach to breast cancer treatment.</p><p><strong>Graphical abstract: </strong>The molecular docking study of Dihydrogingerenone A, 1-(3, 4-dihydroxy-5-methoxyphenyl)-7-(3, 4-dihydroxyphenyl) heptane-3, 5-diyldiacetate, and Dihydrogingerenone C from <i>Aframomum melegueta</i> as effective breast cancer treatment.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054614","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":"Therapeutic exploration potential of adenosine receptor antagonists through pharmacophore ligand-based modelling and pharmacokinetics studies against Parkinson disease.","authors":"Abduljelil Ajala, Otaru Habiba Asipita, Abatyough Terungwa Michael, Murtala Taiwo Tajudeen, Ibrahim A Abdulganiyyu, Ramith Ramu","doi":"10.1007/s40203-025-00305-9","DOIUrl":"10.1007/s40203-025-00305-9","url":null,"abstract":"<p><p>Parkinson's Disease (PD) is a neurodegenerative disorder that primarily affects persons aged 65 and older. It leads to a decline in motor function as a result of the buildup of abnormal protein deposits called Lewy bodies in the brain. Existing therapies exhibit restricted effectiveness and undesirable side effects. The objective was to discover potent medications that have demonstrated effectiveness in treating PD by employing computational methods. This work employed a comprehensive approach to evaluate 70 pyrimidine derivatives for their potential in treating PD. The evaluation involved the use of QSAR modelling, virtual screening, molecular docking, MD simulation, ADMET analysis, and antagonist inhibitor creation. Six compounds passed all the evaluation, while for MD simulation, carried out between the compound with best docking score and the reference drug, compound 57 was discovered to possess more stability compared to theophylline which is the reference drug, and it functions as a primary inhibitor of the adenosine A_2A receptor. Additionally, the study determined that compound 57 satisfied the Rule of Five (Ro5) standards and exhibited robust physicochemical characteristics. The compound exhibited moderate to low levels of hERG inhibition. The conducted investigations highlighted promising outcomes of natural compounds that can orient towards the rational development of effective Parkinson's disease inhibitors.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00305-9.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054615","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":"Multilayered screening for multi-targeted anti-Alzheimer's and anti-Parkinson's agents through structure-based pharmacophore modelling, MCDM, docking, molecular dynamics and DFT: a case study of HDAC4 inhibitors.","authors":"Nikita Chhabra, Balaji Wamanrao Matore, Nisha Lakra, Purusottam Banjare, Anjali Murmu, Arijit Bhattacharya, Shovanlal Gayen, Jagadish Singh, Partha Pratim Roy","doi":"10.1007/s40203-024-00302-4","DOIUrl":"10.1007/s40203-024-00302-4","url":null,"abstract":"<p><strong>Abstract: </strong>Alzheimer's disease (AD) and Parkinson's disease (PD) are neurological conditions that primarily impact the elderly having distinctive traits and some similarities in terms of symptoms and progression. The multifactorial nature of AD and PD encourages exploring potentiality of multi-target therapy for addressing these conditions to conventional, the \"one drug one target\" strategy. This study highlights the searching of potential HDAC4 inhibitors through multiple screening approaches. In this context, structure-based pharmacophore model, ligand profiler mapping and MCDM approaches were performed for target prioritization. Similarly, ligand profiler, MCDM and Docking studies were performed to prioritize multi-targeted HDAC4 inhibitors. These comprehensive approaches unveiled 5 common targets and 5 multi-targeted prioritized compounds consensually. MD simulations, DFT and binding free energy calculations corroborated the stability and robustness of propitious compound 774 across 5 prioritized targets. In conclusion, the screened compound 774 (ChEMBL 4063938) could be a promising multi-targeted therapy for managing AD and PD further rendering experimental validation.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00302-4.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030516","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":"Comparative analysis of the genomic and expression profiles of ANLN and KDR as prognostic markers in breast Cancer.","authors":"Aamir Mehmood, Rongpei Li, Aman Chandra Kaushik, Dong-Qing Wei","doi":"10.1007/s40203-024-00301-5","DOIUrl":"10.1007/s40203-024-00301-5","url":null,"abstract":"<p><p>Breast cancer (BC) remains a highly heterogeneous disease, complicating diagnosis and treatment. This study investigates the prognostic significance of Anillin (<i>ANLN</i>) and Kinase Insert Domain Receptor (<i>KDR</i>) genes, focusing on their mutational and expression landscapes in BC using data from The Cancer Genome Atlas (TCGA). We found that high <i>ANLN's</i> expression is strongly associated with poor overall survival, highlighting its potential as a robust prognostic marker. In contrast, <i>KDR</i>, despite its higher mutation frequency, showed a less significant correlation with survival outcomes. Machine learning (ML) models incorporating transcriptional and translational data further supported <i>ANLN's</i> prognostic value, demonstrating superior accuracy in survival stage prediction when both genes were analyzed together. Functional enrichment analysis revealed that <i>ANLN</i> is primarily involved in cell cycle regulation, while <i>KDR</i> is linked to angiogenesis, suggesting that combined targeting of these pathways could enhance therapeutic efficacy. These findings underscore the potential of <i>ANLN</i> and <i>KDR</i> as complementary biomarkers in BC prognosis and highlight the need for further validation in diverse cohorts.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00301-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018675","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":"Insights into structural and binding studies of pollen allergen Bet v 1 using computational approaches.","authors":"Mansi Pandit, Nandita Narayanasamy, N Latha","doi":"10.1007/s40203-024-00303-3","DOIUrl":"10.1007/s40203-024-00303-3","url":null,"abstract":"<p><p>Bet v 1, the European White Birch tree pollen allergen is responsible for a number of allergic responses in humans such as rhinitis, asthma and oral allergy syndrome. The allergen belongs to pathogenesis-related (PR) class 10 protein superfamily and exists in several naturally occurring isoforms. Limited structural information on Bet v 1 isoallergens and variants prompted us to carry out their in silico structural characterization. In this study, three-dimensional structures of Bet v 1 isoallergens were predicted followed by allergen-antibody docking with Bet v 1- specific human IgE. Further, molecular dynamics simulations were performed for the allergen-antibody complexes. In addition, in silico mutagenesis was carried out for the design of a hypoallergenic variant of Bet v 1. Our study aimed to elucidate the differential ability of Bet v 1 isoallergens in eliciting allergic responses based on structural features and also identified a potential hypoallergen allowing us to propose it as a promising candidate for treating birch pollen-induced allergy.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00303-3.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980985","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":"Identification of potential MMP-8 inhibitors through virtual screening of natural product databases.","authors":"Yi Wang, Xiushan Chen","doi":"10.1007/s40203-024-00299-w","DOIUrl":"https://doi.org/10.1007/s40203-024-00299-w","url":null,"abstract":"<p><p>Matrix metalloproteinase-8 (MMP-8), a type II collagenase, is a key enzyme in the degradation of collagens and is implicated in various pathological processes, making it a promising target for drug discovery. Despite advancements in the development of MMP-8 inhibitors, concerns over potential adverse effects persist. This study aims to address these concerns by focusing on the development of novel compounds with improved safety profiles while maintaining efficacy. In this study, we employed a computational approach to screen potent and safe inhibitors of MMP-8 from the Natural Product Activity and Species Source Database (NPASS). Initially, we constructed a pharmacophore model based on the crystal structure of the MMP-8-FIN complex (PDB ID: 4EY6) utilizing the Pharmit tool. This model then guided the selection of 44 promising molecules from NPASS, setting the stage for further analysis and evaluation. We comprehensively evaluated their drug-likeness and toxicity profiles. Molecules 21, 4, and 44 were identified as potentially effective MMP-8 inhibitors through a robust pipeline that included ADMET profiling, molecular docking, and molecular dynamics simulations. Notably, molecule 21 stood out for its low toxicity, high binding stability, and favorable ADMET profile, while molecule 44 demonstrated excellent affinity. These compounds offer structural novelty compared to known MMP-8 inhibitors. These computational results can be combined with in vitro experiments in the future to validate their activity and safety. These findings provide an important reference for drug design of MMP-8 inhibitors.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960489","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}