In silico pharmacology最新文献

{"title":"Oral absorption of semaglutide: pharmacokinetic modeling and molecular dynamics simulations.","authors":"Palak Nitin Agarwal, Ian S Haworth","doi":"10.1007/s40203-025-00393-7","DOIUrl":"10.1007/s40203-025-00393-7","url":null,"abstract":"<p><p>Semaglutide is a GLP-1 receptor agonist that is formulated for oral administration as Rybelsus®. Structurally, semaglutide is a lipid-modified alpha-helical peptide and its absorption, which occurs mainly from the stomach, may be dependent on its conformational properties. Therefore, it is important to include three-dimensional structural parameters that reflect conformation in a pharmacokinetic model of semaglutide. We used pharmacokinetic modeling to simulate the absorption of semaglutide and identify molecular and physiological parameters that may govern this process. A molecular radius of 5.8 Å and a gastric pore radius of 10.25 Å were required to reproduce the observed stomach absorption and plasma concentration vs. time profile of oral semaglutide at a dose of 10 mg. To determine if this molecular radius can be achieved conformationally, molecular dynamics simulations were performed. These simulations showed that the linker-lipid chain of semaglutide wraps around the peptide alpha-helix and produces a helical structure with an average molecular radius (including the peptide, linker and lipid) that falls in the same range as that required in the pharmacokinetic model. Therefore, this linker-lipid wrapping may be necessary for semaglutide to be absorbed into the systemic circulation. This work shows the potential for using molecular modeling in parameterization of pharmacokinetic models for molecules in which conformational variability may influence the pharmacokinetics.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00393-7.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"103"},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677058","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":"Inward opening (IO) to outward opening (OO) 'catalytic transition' and OO to IO 'relaxation' of P-glycoprotein: to investigate the role of helices in efflux through targeted molecular dynamics simulation.","authors":"Pranabesh Mandal, Priyanka Rani, Durg Vijay Singh","doi":"10.1007/s40203-025-00389-3","DOIUrl":"https://doi.org/10.1007/s40203-025-00389-3","url":null,"abstract":"<p><p>P-glycoprotein (P-gp) is a membrane protein that effluxes xenobiotics across cell membranes via ATP hydrolysis. It is overexpressed mainly in cancer cells and is responsible for multidrug resistance by effluxing chemotherapeutic molecules. To unearth the coordinated mechanism and function of different domains i.e., nucleotide binding domain (NBD), transmembrane domain (TMD) and transmembrane helices (TMHs) in catalysis, human P-gp was modelled in Inward Opening (IO) and Outward Opening (OO) states and further subjected to targeted molecular dynamics (tMD) simulations. Structural transition frames between IO ⇌ OO were obtained from the clustering of tMD simulation trajectories. Protein model quality scores (ProSA Z-scores) were evaluated for conformational states. The results showed that the IO → OO transition is an energetically uphill process requiring a major structural transition involving 131 distinct conformational states, coupled with ATP hydrolysis. In contrast, the OO → IO relaxation, crucial for resetting the transporter, does not follow the same transition pathway and is an energetically downhill process involving only 90 states, indicating a faster and distinct mechanism. The helix pairs 1&7 and 6&12 are observed to be relatively static, forming the core of the TMD, while pairs 3&9 and 4&10 are moderately dynamic, and pairs 5&11 and 2&8 are highly dynamic, located more peripherally. The static and dynamic nature and position of these helix pairs justify their respective roles in substrate binding and efflux, and these findings may provide insight into the design and development of next-generation P-gp inhibitors.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00389-3.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"102"},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661416","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":"In silico evaluation and therapeutic targeting of LVDD9B protein for WSSV inhibition: molecular and ecological insights for aquaculture solutions.","authors":"Md Iftehimul, Neaz A Hasan, Mst Farzana Akter, Md Arju Hossain, Sajia Afrin Tima, Amirul Kabir, Prottay Choudhury, Apurbo Bhowmick, Sakib Anzum Pranto, Ali Mohamod Wasaf Hasan, Siddique Akber Ansari, Md Habibur Rahman","doi":"10.1007/s40203-025-00390-w","DOIUrl":"https://doi.org/10.1007/s40203-025-00390-w","url":null,"abstract":"<p><p>This study aimed to investigate structural dynamics, binding interactions, stability, pharmacokinetics, ecological risks, and bioactivity of shrimp receptor protein LVDD9B to identify potential therapeutic candidates against White Spot Syndrome Virus (WSSV). LVDD9B protein's 3D structure was predicted using SWISS-MODEL and validated with ProSA and Ramachandran plots. Protein-protein docking between LVDD9B and VP26 (WSSV protein) was performed using HADDOCK 2.4 server. Molecular docking, dynamics simulations, binding-free energy calculations, principal component analysis (PCA), electrostatic, and vibrational frequency analyses evaluated binding affinity, stability and polarity of complexes. The 128-amino-acid LVDD9B protein was predominantly localized in the cytoplasm and extracellular with stable, and hydrophilic, with structural analysis identified key secondary structures and conserved chitin-binding sites. Docking studies revealed strong interactions between LVDD9B and VP26, supported by hydrogen-bonds and salt bridges. Molecular dynamics simulations demonstrated stable complexes with minimum fluctuating RMSF values, and MM/GBSA calculations indicated favourable binding free energies. Pharmacokinetic analysis highlighted promising bioavailability and drug-like properties for Luteolin and Quercetin from <i>Cuscuta reflexa</i>, while ecological assessment identified Cosmosiin as least hazardous, with Quercetin and Luteolin showing higher toxicity. PCA revealed stable protein-ligand complexes with flexibility in Apo form. Isorhoifolin exhibited the lowest internal energy (-2099.4722 Hartree) and highest dipole moment (8.1833 Debye). Frontier orbital analysis showed HOMO-LUMO gaps (4.05-4.34 eV) influencing reactivity, while MEP and vibrational frequency analyses supported compound stability and bioactivity. This study explores LVDD9B's structural and interaction dynamics for developing antiviral therapy against WSSV, highlighting therapeutic potential of Cosmosiin, Isorhoifolin and Afzelin based on their pharmacokinetic and ecological profiles.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00390-w.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"101"},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144628337","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":"Atomic-level binding interaction analysis of <i>Mycobacterium tuberculosis</i> membrane protein Rv1085c with Toll-Like receptor 2 to investigate its role in immune response.","authors":"Logesh Radhakrishnan, Irfan Navabshan, V Lavanya, Shazia Jamal, Neesar Ahmed","doi":"10.1007/s40203-025-00388-4","DOIUrl":"https://doi.org/10.1007/s40203-025-00388-4","url":null,"abstract":"<p><p>The sequencing of the entire <i>Mycobacterium tuberculosis</i> (Mtb) genome in 1998 opened the door to exciting discoveries about the cellular and molecular underpinnings of the pathogen's virulence and capability to persist within host cells. One of the potential contributing gene to this virulence and persistence is Rv1085c, which is a potential membrane protein in the Mtb H37Rv strain. Rv1085c has been annotated in databases such as MycoBrowser; however the structural and functional characteristics of Rv1085c have not been addressed in detail. In this study, we conducted an in silico structural and functional characterization of Rv1085c to further our understanding of its potential role in Mtb virulence. The 3D model of the Rv1085c protein was generated using the I-TASSER server and subjected to structural validation using a number of tools including PROCHECK, ProSA-web and Verify3D. Functional predictions provided evidence to suggest Rv1085c could be involved in processes related to virulence, detoxification pathway and host adaptation. Protein-protein docking studies were performed to examine potential host-pathogen interactions using ZDOCK and docking of Rv1085c against Toll-like receptor 2 (TLR2) (PDB ID: 5D3I), an important receptor that participates in innate immune recognition of Mtb. Molecular dynamics simulations (MDS) were also performed to analyse the stability and conformational dynamics of the Rv1085c-TLR2 complex. These results provide preliminary insights on structure and interaction with Rv1085c, suggesting its potential role in host immune modulation. This research offers insights for ulterior experimental verifications and may lead to a better identification of drug targets related to tuberculosis.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"100"},"PeriodicalIF":0.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610718","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":"Exploring the therapeutic potential of <i>Momordica charantia</i> in targeting protein kinase C delta (PRKCD) for type 2 diabetes mellitus: insights from network pharmacology, molecular docking, and molecular dynamics simulations.","authors":"Ruchi Yadav, Nidhi Nambiar, Manushi Shah, Bhumika D Patel","doi":"10.1007/s40203-025-00385-7","DOIUrl":"https://doi.org/10.1007/s40203-025-00385-7","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a chronic condition caused by decreased insulin production and increased insulin resistance. Current treatments for T2DM include pharmacological agents and lifestyle modifications, but their clinical applications have become limited due to their side effects and high cost. Herbal remedies and natural products have become popular alternative treatments as they are associated with fewer side effects. <i>Momordica charantia</i> Linn. (bitter melon) is a member of the Cucurbitaceae family and has been used as a traditional anti-diabetic remedy in various countries for many years. The plant contains several biologically active compounds, including glycosides, saponins, alkaloids, triterpenes, proteins, and steroids. The hypoglycemic activity of <i>Momordica charantia</i> is primarily attributed to its saponins, which are collectively known as charantins and alkaloids. Through network pharmacology, molecular docking and MD simulation studies, we found underlying mechanism of karela in the treatment of T2DM. The network pharmacology study concluded the Protein kinase C delta (PRKCD) as a hub gene out of 49 probable target genes. Various published studies have also asserted the pathophysiological role of PRKCD in the development of T2DM. Molecular docking study identified the top three active phytoconstituents of karela; Momordicoside C, Momorcharaside B and Momordin I, with docking scores of - 8.0 kcal/mol, - 7.9 kcal/mol, and - 7.9 kcal/mol, respectively. MD simulation studies concluded the Momordicoside C and Momorcharaside B as promising hit candidates to experimentally validate for their in vitro activity against the Protein kinase C delta. Overall, present research work highlighted the new mechanism of action of a well-known plant, Karela, in the treatment of T2DM.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"99"},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602620","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":"Comprehensive immunoinformatics guided design and in silico assessment of a multi-epitope vaccine to elicit immunity against Mayaro virus.","authors":"Md Mashiur Rahaman, Mahmudul Hasan, G M Nurnabi Azad Jewel, Sumaiya Hasan, Shamsul H Prodhan, Hammadul Hoque","doi":"10.1007/s40203-025-00387-5","DOIUrl":"https://doi.org/10.1007/s40203-025-00387-5","url":null,"abstract":"<p><p>The Mayaro virus (MAYV), an emerging arbovirus of the Alphavirus genus (family Togaviridae), shares clinical and epidemiological features with other arboviruses such as Chikungunya, Dengue, and Zika. It causes Mayaro fever in humans, characterized by febrile illness and prolonged arthralgia, often leading to misdiagnosis. Given the absence of licensed vaccines or antiviral therapies and the presence of competent vectors in endemic regions, MAYV poses a significant threat of epidemic, particularly in rural South America. In this research, computational immunological methods were employed to construct a polypeptide vaccine, with a focus on the structural polyprotein of the Mayaro virus. A series of rigorous computational assessments were used to predict the most potent T and B lymphocyte epitopes for the vaccine candidate. The vaccine exhibited favorable physicochemical properties, stable secondary and tertiary structures, and high solubility. Molecular dynamics simulations demonstrated its structural stability, while docking studies indicated robust interactions with TLR2 and TLR4 receptors, essential for initiating immune responses. Codon optimization, along with in silico cloning, demonstrated efficient expression of the vaccine candidate in an <i>E. coli</i> system. Finally, an immune simulation indicated that the vaccine candidate could induce a robust and long-lasting immune response.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00387-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"98"},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602619","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":"Lupeol acetate from <i>Cleome viscosa</i> as a therapeutic candidate for myocardial infarction.","authors":"James Diokadan, Ishimwe Aimée Divine, Shamasamu Emma, Rutendo Samantha Makiwa, Uwizera Celine, Lucky Nicholus, Ssekikubo Ronald, Sreya Kosanam, Rajeshwari Pasupula","doi":"10.1007/s40203-025-00383-9","DOIUrl":"https://doi.org/10.1007/s40203-025-00383-9","url":null,"abstract":"<p><strong>Background: </strong>Lupeol acetate, a naturally occurring pentacyclic triterpenoid with anti-inflammatory, antioxidant, and cardioprotective properties, was identified from the methanolic extract of <i>Cleome viscosa</i> leaves as a promising therapeutic candidate for myocardial infarction (MI), based on its favorable pharmacokinetic and safety profile.</p><p><strong>Methods: </strong>The methanolic extract of <i>Cleome viscosa</i> was analyzed using gas chromatography-mass spectrometry (GC-MS) to identify bioactive compounds. Pharmacokinetics, drug-likeness, and toxicity were assessed using SwissADME, MolSoft, and ProTox-II tools. Differentially expressed genes (DEGs) from MI datasets were integrated with small-molecule targets through Protein-protein interaction (PPI) networks were construction followed by weighted gene co-expression network analysis (WGCNA) to identify key hub genes. Molecular dynamics simulations validated the stability of the interactions between lupeol acetate and target proteins.</p><p><strong>Results: </strong>Among 32 identified compounds, lupeol acetate exhibited favorable pharmacokinetics, low toxicity, and high drug-likeness. WGCNA revealed JAK2, a key regulator of inflammatory pathways and immune signaling, as a critical hub gene associated with MI-related mechanisms, including apoptosis and inflammation. Molecular docking demonstrated strong binding between lupeol acetate and JAK2, which was confirmed by molecular dynamics simulations showing a stable protein-ligand complex.</p><p><strong>Conclusion: </strong>This study identifies lupeol acetate as a promising cardioprotective candidate. By integrating WGCNA with computational analyses, it provides novel insights into the molecular mechanisms of <i>Cleome viscosa</i>. These findings support further in vivo validation and development of lupeol acetate for therapeutic use in myocardial infarction.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00383-9.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"97"},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577358","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>I</i> <i>n-silico</i> drug repurposing for lysyl oxidase inhibition and ferroptosis prevention in epilepsy.","authors":"Shrajal Kumari, Gajendra Choudhary, Ajay Prakash, Bikash Medhi","doi":"10.1007/s40203-025-00373-x","DOIUrl":"10.1007/s40203-025-00373-x","url":null,"abstract":"<p><p>Epilepsy represents a prevalent symptom across various neurological disorders, which is characterized by the abnormal firing of neurons from diverse brain regions, resulting in impulsive frequent seizures, protracted seizures can cause cell death and neuronal damage. Ferroptosis, recently acknowledged as a regulated form of cell death, involves the excessive deposition of iron ions culminating in the build-up of harmful lipid-based reactive oxygen species. Some recent research findings have suggested that lysyl oxidase (LysOx) depicts a vital role in the development of various neurological diseases, yet the precise mechanism behind it is still not obscure. This study is done to study the mechanism of how LysOX leads to ferroptosis leading to epileptogenesis. We have screened compounds from FDA-approved libraries, and molecules with top docking scores were selected. Pharmacokinetic property, mainly its capability to permeate the blood-brain barrier is important for therapeutic compounds. In this extensive study, we executed virtual screening using an in-silico approach to identify a novel therapeutic compound, capable of targeting LysOX. We used an FDA-approved library to analyze the capability of ligands with LysOX. furthermore, ADMET was also performed (Absorption, Distribution, Metabolism, Excretion, Toxicity) profiling, and molecular dynamics simulations, to identify the most capable compounds. Our elaborate computational study uncovered a set of highly encouraging compounds. These compounds showed great results in inhibiting LysOX and preventing the ferroptotic cell death mechanism which leads to epilepsy.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00373-x.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"96"},"PeriodicalIF":0.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531969","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":"Machine learning prediction of intestinal α-glucosidase inhibitors using a diverse set of ligands: a drug repurposing effort with drugBank database screening.","authors":"Adeshina I Odugbemi, Clement Nyirenda, Alan Christoffels, Samuel A Egieyeh","doi":"10.1007/s40203-025-00384-8","DOIUrl":"10.1007/s40203-025-00384-8","url":null,"abstract":"<p><p>The global rise in diabetes mellitus (DM) poses a significant health challenge, necessitating effective therapeutic interventions. α-Glucosidase inhibitors play a crucial role in managing postprandial hyperglycemia and reducing the risk of complications in Type 2 DM. Quantitative Structure-Activity Relationship (QSAR) modelling is critical in computational drug discovery. However, many QSAR studies on α-glucosidase inhibitors often rely on limited compound series and statistical methods, restricting their applicability across wide chemical space. Integrating machine learning (ML) into QSAR offers a promising avenue for discovering novel therapeutic compounds by handling complex information from diverse compound sets. Our study aimed to develop robust predictive models for α-glucosidase inhibitors using a dataset of 1082 compounds with known activity against intestinal α-glucosidase (maltase-glucoamylase). After data preparation, we used 626 compounds to train ML models, generating different training data of three distinct molecular representations: 2D-descriptors, 3D-descriptors, and Extended-connectivity-fingerprint (ECFP4). These models, trained on random forest and support vector machine algorithms, underwent rigorous evaluation using established metrics. Subsequently, the best-performing model was used to screen the Drugbank database, identifying potential α-glucosidase inhibitor drugs. Drug repurposing, an expedited strategy for identifying new therapeutic uses for existing drugs, holds immense potential in this regard. Molecular docking and molecular dynamics simulations further corroborated our predictions. Our results indicate that 2D descriptors and ECFP4 molecular representations outperform 3D descriptors. Furthermore, drug candidates identified from DrugBank screening exhibited promising binding interactions with α-glucosidase, supporting our ML predictions and their potential for drug repurposing.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00384-8.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"95"},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510082","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":"Anti-lipidemic and anti-diabetic properties of <i>Gymnema sylvestre</i> saponins: an in-silico approach.","authors":"R Archana Preetha, G Dicky John Davis, M Gowri Neelima, B S Chaitra, B Kirankumar","doi":"10.1007/s40203-025-00369-7","DOIUrl":"10.1007/s40203-025-00369-7","url":null,"abstract":"<p><p>Diabetes mellitus and dyslipidemia make a significant contribution to mortality and morbidity. The <i>Gymnema Sylvestre's</i> saponins have a variety of pharmacological effects, including the possibility of lowering diabetes and cholesterol levels. In the present study, molecular docking and molecular dynamic simulations were used in silico in order to understand the protein league stability and molecular interactions by aiming at anti-diabetic and anti-lipidemic proteins. As well we performed the drug likeliness and its toxicity of 13 <i>G. sylvestre</i> saponins, against anti-diabetic target proteins Aldose reductase, α- amylase, α- glycosidase and antilipidemic target proteins HMG-CoA reductase, Fatty acid synthase, Pancreatic Lipase target proteins. <i>Gymnemasin B</i> and <i>Gymnema saponin- IV</i> were shown the high energy between the target protein. As well these compounds shown good ADMET properties with standard oral antidiabetic compound Linagliptin. Molecular dynamics simulations further supported their strong binding interactions with the target proteins over time using 100 ns MD simulations. These findings suggest that these saponins hold promise as potential active molecules to making them possible candidates for the development of novel therapies for diabetes mellitus.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00369-7.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"94"},"PeriodicalIF":0.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478273","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}