In silico pharmacology最新文献

{"title":"Evaluating the neuroprotective potential of <i>Mucuna pruriens</i> and <i>Boswellia serrata</i> in Huntington's disease: an integrative bioinformatics approach.","authors":"Pallavi V Bhosle, Sailesh J Wadher","doi":"10.1007/s40203-025-00398-2","DOIUrl":"10.1007/s40203-025-00398-2","url":null,"abstract":"<p><p>Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by CAG repeat expansion in the HTT gene, leading to oxidative stress, mitochondrial dysfunction, and neuroinflammation. Conventional therapies offer only symptomatic relief with limited efficacy. This study aimed to explore the neuroprotective potential of <i>Mucuna pruriens</i> (MP) and <i>Boswellia serrata</i> (BS) through an integrative bioinformatics approach, targeting multiple pathological mechanisms implicated in HD. Phytoconstituents from MP and BS were selected based on pharmacokinetic properties, including drug-likeness and blood-brain barrier permeability. Differential gene expression analysis was performed using GEO datasets to identify HD-related genes. Target prediction, network pharmacology, protein-protein interaction (PPI) network construction, and pathway enrichment analyses were carried out. Key proteins were subjected to molecular docking using AutoDock Vina and stability was evaluated through molecular dynamics simulations. A total of 47 phytoconstituents were identified, associated with 1333 (MP) and 693 (BS) potential targets. Network pharmacology revealed the involvement of PI3K-Akt, MAPK, NF-kappa B, and neurotrophin signaling pathways. AKT1, MAPK1, and SLC6A3 emerged as central hub proteins. Molecular docking demonstrated strong binding affinities of levodopa, tyrosine, and phenylalanine with core HD-related proteins (AKT1, EGFR, and SLC6A3). Molecular dynamics simulations further confirmed complex stability, with RMSD values ranging between 1.8 and 3.2 Å across key ligand-protein pairs supporting their neuroprotective potential. This integrative bioinformatics analysis highlights that phytoconstituents from <i>Mucuna pruriens</i> and <i>Boswellia serrata</i> modulate key molecular pathways involved in HD pathogenesis. MP exhibited antioxidative and dopamine-enhancing effects, while BS showed significant anti-inflammatory effects. These findings suggest that MP and BS may serve as promising plant-based therapeutic candidates for HD, warranting further in vitro and in vivo validation.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00398-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"123"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12401820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994818","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":"Salinity-induced capsaicin biosynthesis in <i>Capsicum annuum</i> L.: mechanistic and molecular insights into its potential role in prostate adenocarcinoma.","authors":"Amantika Singh, Krishna Kumar Choudhary","doi":"10.1007/s40203-025-00416-3","DOIUrl":"10.1007/s40203-025-00416-3","url":null,"abstract":"<p><p>Prostate cancer incidence is expected to double by 2040, with related deaths rising by 80% highlighting the urgent need for effective prevention and treatment strategies. This growing concern has increased interest in utilising natural plant compounds for cancer therapies. Capsaicin, a key component of <i>Capsicum annuum</i> L., is well renowned for its anti-cancerous properties. Results of quantitative UHPLC-HRMS analysis revealed that capsaicin accumulation was significantly increased in fruits of <i>Capsicum annum</i> L. treated with 50 and 100 mM salinity compared to control (0 mM). These findings suggest that salinity stress enhanced anti-cancer potential of <i>Capsicum annuum</i> L. while presenting a sustainable solution for utilizing salinity-affected lands to enhance capsaicin production. To elucidate capsaicin mechanism against prostate adenocarcinoma, five hub targets were identified through network pharmacology and protein-protein interaction network analysis. KEGG pathway analysis revealed four key targets (ERBB2, HSP90AA1, MTOR, and PIK3CA) involved in tumour growth, cell proliferation, and survival via the PI3K-Akt, MAPK, and androgen receptor pathways. Gene (GEPIA2) and protein expression analysis (Human Protein Atlas) confirmed their overexpression in prostate adenocarcinoma cells, underscoring their therapeutic relevance. Docking studies along with molecular dynamic simulations further demonstrated significant binding affinities between capsaicin and these targets (ERBB2: - 6.207; HSP90AA1: - 4.846; MTOR: - 6.451 and PIK3CA: - 6.720 Kcal/mol) suggest that capsaicin may disrupt the PI3K/Akt/mTOR and MAPK signaling pathways, potentially leading to the suppression of prostate cancer. Our Insilco based findings suggest that capsaicin interacts with key molecular targets associated with prostate cancer pathways, further in vivo validations are necessary to confirm its therapeutic potential.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"122"},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983889","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":"Computational elucidation of <i>Plasmodium falciparum</i> enoyl-ACP reductase inhibition by <i>Salacia debilis</i> compounds: adaptive ligand binding drives antimalarial activity.","authors":"Prince Manu, Muntawakilu Padiga Seidu, Alice Adomako, Caleb Kusi Asamoah, Ophelia Duodu, Akyana Britwum, Michael Konney Laryea, Godfred Darko, Lawrence Sheringham Borquaye","doi":"10.1007/s40203-025-00413-6","DOIUrl":"10.1007/s40203-025-00413-6","url":null,"abstract":"<p><strong>Abstract: </strong>Malaria remains a critical global health challenge due to rising <i>Plasmodium falciparum</i> resistance. Natural products are a rich source of novel antimalarials; extracts of <i>Salacia debilis</i> (SD) have shown potent antiplasmodial effects. Here, three <i>S. debilis</i>-derived isolates: SD03 (benzyl 2-methoxybenzoate), SD04 (1,10-dihydroxy-6H-benzo[c]chromen-6-one) and SD05 (8-hydroxy-3,4-dimethoxydibenzo[b,d]furan-1-carboxylic acid) were investigated to identify their molecular target. Highthroughput screening and molecular docking revealed <i>P. falciparum</i> enoylacyl carrier protein reductase (PfENR), an enzyme in the parasite's type II fatty acid biosynthesis pathway absent in humans, as the primary target, with binding affinities of - 8.50 to - 8.90 kcal/mol. Extended 500 ns molecular dynamics (MD) simulations confirmed stable, conformation-specific ligand-enzyme complexes. The isolates' interaction footprints closely match those of triclosan, a benchmark PfENR inhibitor, by engaging key active site residues (Tyr111, Tyr267, Leu315) and trapping the enzyme in inactive states. These results establish a mechanistic basis for the antiplasmodial activity of <i>S. debilis</i> isolates and validate PfENR as a target for selective antimalarial development. SD04 emerged as the lead candidate based on favorable pharmacokinetic predictions, highlighting its potential for structure-guided optimization against drug-resistant malaria.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00413-6.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"121"},"PeriodicalIF":0.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12390918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983897","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>Cinnamomum verum</i> and <i>Coriandrum sativum</i> secondary metabolites exhibit neuroprotective potential: insights from in vitro, ex vivo and computational models.","authors":"Ayodeji O Falade, Megan D Akingbasote, Kayode E Adewole, Odunayo M Agunloye, Ahmed A Ishola, Aimen Aljoundi, Ghazi Elamin, Kolawole A Olofinsan","doi":"10.1007/s40203-025-00412-7","DOIUrl":"10.1007/s40203-025-00412-7","url":null,"abstract":"<p><p>Cinnamon and coriander plants are sources of popular spice products in different cuisines prepared by many people worldwide. The inhibitory effect of cinnamon bark and coriander seeds aqueous extracts on butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) activities, and their antioxidant properties were investigated using in vitro, molecular docking and molecular dynamics (MD) computational models. Standard experimental methods were employed to determine the plant extracts' antioxidant and enzyme-inhibitory capacities. Subsequently, chemically annotated metabolites from the extracts were subjected to MD with the enzymes before the ligand-protein complexes of two compounds with the highest docking scores were subjected to MD at 300 ns. Phytochemical profiling of extracts from the plants via Gas Chromatography-Mass Spectrometry analysis revealed the presence of polyphenols, flavonoids, terpenes and their derivatives. The extracts from the plant inhibited the investigated cholinergic proteins, although no significant differences (<i>p</i> > 0.05) were observed in the IC₅₀ values for their activities. While both extracts demonstrated good antioxidative activities, the cinnamon extract exhibited better radical scavenging and Fe-chelation abilities, while the coriander extract exhibited superior ferric-reducing properties. Amongst the chemical compounds identified from the plants' extract, chlorogenic acid with - 31.87 kcal/mol & - 39.29 kcal/mol and rutin with - 48.27 kcal/mol & - 54.37 kcal/mol MM/GBSA computed scores exhibited more negative binding affinity, thus showed potential to be the dominant inhibitors of the AChE and BChE enzymes, respectively. The 300 ns MD results revealed that the proteins' structure was stable after binding of the spice phytoconstituents. Further activity-guided isolation experiment is required to determine the spices as viable sources of these neuroprotective polyphenols.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"120"},"PeriodicalIF":0.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12390917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983655","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 dual inhibitors of ROCK1 and TGFBR1 for overcoming metastasis: an integrated pharmacophore and docking driven CADD strategy.","authors":"Bikashita Kalita, Mohane Selvaraj Coumar","doi":"10.1007/s40203-025-00414-5","DOIUrl":"10.1007/s40203-025-00414-5","url":null,"abstract":"<p><p>Rho-associated coiled-coil kinase 1 (ROCK1) and transforming growth factor-beta receptor 1 (TGFBR1) plays crucial roles in epithelial-mesenchymal transition (EMT), cytoskeleton remodeling, cell adhesion, and tumor metastasis. Targeting both ROCK1 and TGFBR1 simultaneously offers a strategic approach to disrupt these pathways, potentially leading to more effective treatments for cancer metastasis. To identify dual inhibitors, a multifaceted computational approach integrating pharmacophore modeling, molecular docking, and molecular dynamics (MD) simulations was employed. Pharmacophore models were derived from the PDB structures of ROCK1 and TGFBR1 and validated based on their ability to discriminate between known active and inactive inhibitors from the ChEMBL database with performance evaluated using Receiver Operating Characteristic Area Under the Curve (ROC AUC) calculations. These validated pharmacophore models were used to virtually screen a diverse set of 1,48,648 compounds, identifying promising candidates for dual inhibition. Top-ranking compounds from the pharmacophore screening were subjected to molecular docking studies to evaluate their binding interactions with ROCK1 and TGFBR1. The most promising candidates, Hit-1, Hit-2, and Hit-3, were further analyzed through 200-ns molecular dynamics simulations to assess their stability and interaction dynamics with the hinge residues of both targets. Among the screened compounds, Hit-2, (4-(1,3-dimethyl-1H-pyrazol-4-yl)-N-[2-(pyridin-3-yloxy)propyl]pyrimidin-2-amine) exhibited the most favourable binding affinity (- 155.801 kJ/mol) for ROCK1 and (- 213.264 kJ/mol) for TGFBR1, structural stability, and interaction profile, suggesting its potential as a dual inhibitor of ROCK1 and TGFBR1.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00414-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"119"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983884","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":"Computational assessment of natural compounds as potential hexokinase 2 inhibitors.","authors":"Abdullahi Ibrahim Uba, Eleonora Procino, Lorenza Marinaccio, Adriano Mollica, Gokhan Zengin","doi":"10.1007/s40203-025-00404-7","DOIUrl":"10.1007/s40203-025-00404-7","url":null,"abstract":"<p><p>Hexokinase 2 (HK2), a central enzyme in the glycolytic pathway, is frequently overexpressed in malignant cells, contributing to enhanced glucose metabolism and tumor progression. Despite its recognized role in cancer metabolism, effective and selective HK2 inhibitors from natural sources remain underexplored. This study aimed to identify promising natural product inhibitors of HK2 through an integrated computational approach. A diverse set of 100 natural compounds-including phenolics, terpenoids, alkaloids, and anthraquinones-was virtually screened using Glide XP docking to predict binding affinities. Subsequent molecular dynamics (MD) simulations and MM-GBSA binding free energy calculations were performed to validate docking results and evaluate complex stability over time. Notably, several phenolics, particularly salvianolic acid A, salvianolic acid B, verbascoside, quercetin, and hyperoside, exhibited strong binding affinities and favorable interaction profiles. Salvianolic acid A recorded the best docking score (- 9.58 kcal/mol), while hyperoside showed exceptional structural stability during 30 ns MD simulations and a competitive MM-GBSA binding energy (- 42.35 kcal/mol), approaching that of the native ligand (- 55.51 kcal/mol). Structural interaction analysis revealed that hyperoside formed persistent hydrogen bonds with key catalytic residues of HK2 (Glu742, Asp657, Glu708), supporting its potential as a lead scaffold. These findings highlight the value of phenolic natural products as potential HK2 inhibitors and lay the groundwork for future anticancer drug development targeting cancer-specific metabolic pathways.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"118"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983818","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 discovery of alkaloids as VEGFR-2 inhibitors with favorable toxicity profiles: insights from molecular dynamics and MM/GBSA.","authors":"Nalanda da Silva Maués, Nalberth Batista Farias, Davi do Socorro Barros Brasil, Renato Araújo da Costa","doi":"10.1007/s40203-025-00410-9","DOIUrl":"10.1007/s40203-025-00410-9","url":null,"abstract":"<p><p>Aberrant angiogenesis mediated by VEGFR-2 is a hallmark of aggressive cancers and a validated therapeutic target. Although clinical tyrosine kinase inhibitors (TKIs) such as sorafenib have shown efficacy, their use is often limited by significant toxicity. In this study, we employed an integrated in silico approach to identify novel VEGFR-2 inhibitors among alkaloids from Brazilian biodiversity, aiming for high affinity and improved safety profiles. A curated library of alkaloids from the NuBBEDB was screened by molecular docking, and top candidates were subjected to a rigorous evaluation pipeline, including MM/GBSA rescoring, toxicity and ADME prediction, and in-depth post-dynamic analyses of 300 ns simulations, such as hydrogen bond analysis and principal component analysis (PCA). The alkaloids NuBBE_306 and NuBBE_456 emerged with strong binding affinities (ΔGbind = - 50.24 and - 47.37 kcal/mol, respectively) and favorable safety and ADME profiles compared to sorafenib. Crucially, the dynamic analyses revealed that NuBBE_456 stands out by maintaining a network of persistent hydrogen bonds and by mimicking the free energy landscape of sorafenib, stabilizing the same inhibited kinase conformation. These findings identify NuBBE_456 as an exceptional lead candidate, combining robust affinity, dynamic stability, and low predicted toxicity, warranting its prioritization for experimental validation.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00410-9.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 3","pages":"117"},"PeriodicalIF":0.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983894","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 inquest reveal the efficacy of <i>Usnea longissima</i> ach. (A tropical Lichen) against ovarian cancer.","authors":"Soumyajit Das, Shivaleela Biradar, Rosni Jabin, Sutapa Datta, Farishta Yasmin, Babu Rl, Arnab Sen","doi":"10.1007/s40203-025-00408-3","DOIUrl":"10.1007/s40203-025-00408-3","url":null,"abstract":"<p><p>Ovarian cancer being the deadliest malignancy for women, with conventional medication often limited by side effects on normal cell. Phytocompounds based therapies have promising alternative due to their fewer adverse side effects and diverse therapeutic benefits. Lichen shows relationship between algae and fungi, are known for producing unique secondary metabolites with potent bioactivity. In this study, <i>Usnea longissima</i> was investigated for its anticancer properties against ovarian cancer using <i>in-silico</i> approaches such as ADMET screening, molecular docking, molecular dynamics simulation, and network pharmacology. Bioactive compounds were first identified by GC-MS analysis. Phytocompounds were screened out by ADME analysis. Two particular compounds 7-acetyl-1,1,3,4,4,6-hexamethyl tetralin and 1,2-benzenedicarboxylic acid were focused based on their strong their binding affinities. These compounds exhibit significant binding affinities to ovarian cancer proteins such as FGFR3 and AKT1, MSH6 and ESR1 with docking scores of - 9.5, - 9.5, - 8.2, - 8.0 kcal/mol respectively, comparable to the binding affinity of the reference drug Pemigatinib. Simulations yielded extremely satisfactory findings for the protein ligand RMSD and RMSF, Rg, SASA, PSA, MM-GBSA profile and network analysis revealed a strong degree of inter-protein association. Despite the work on lichens, only a limited number of lichen species have been explored for their biological efficacy and their therapeutic potential as medicine. In this study, we highlighted the potential of lichen-derived phytocompounds in ovarian cancer treatment and highlights specially 7-acetyl-1, 1, 3, 4, 4, 6-hexamethyl tetralin as promising candidates for future drug development. Further exploration of lichen metabolites may offer novel, effective, and safer therapeutic strategies against ovarian cancer.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00408-3.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"116"},"PeriodicalIF":0.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857255","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 lichen-derived compounds as potential anti-cervical cancer agents: an DFT and MD simulation analysis.","authors":"Balasubramanian Murugesan, Bharath Somasundram, Gopinath Samykannu, Ponmurugan Karuppiah, Nithya Muthusamy, K Agalya, V Bharathi","doi":"10.1007/s40203-025-00380-y","DOIUrl":"https://doi.org/10.1007/s40203-025-00380-y","url":null,"abstract":"<p><p>Lichen-derived compounds have demonstrated promising anti-cancer potential, attributed to their bioavailability and unique structural properties. This study evaluates the therapeutic efficacy of five lichen compounds-fumarprotocetraric acid, salazinic acid, evernic acid, sekikaic acid, and lobaric acid-against cervical cancer, using molecular docking, density functional theory (DFT), and molecular dynamics (MD) simulations. Drug-likeness validation confirmed that evernic acid, topotecan, and ifosfamide adhere to Lipinski's rule of five. Molecular docking against ten cervical cancer target proteins revealed high binding affinities, with fumarprotocetraric acid (- 10.4 kcal/mol against 1KTZ), salazinic acid (- 10.9 kcal/mol against 2PVF), and evernic acid (- 11.3 kcal/mol against 2BIM) outperforming standard drugs such as topotecan (- 10.2 kcal/mol against 2BIM). ADME (Absorption, Distribution, Metabolism, and Excretion) profiling confirmed favorable pharmacokinetics, with salazinic acid exhibiting the highest human intestinal absorption (89.35%). Bioactivity analysis further supported enhanced activity for lichen compounds (0.0-5.0) compared to standard drugs (- 5.0-0.0). DFT analysis demonstrated lower energy gaps for fumarprotocetraric acid (- 0.1806 eV) and salazinic acid (- 0.1632 eV), indicating high chemical reactivity. MD simulations confirmed greater stability of lichen-protein complexes over anti-cancer drugs, with the 2BIM-evernic acid complex displaying the highest Molecular Mechanics Generalized Born Surface Area (MMGBSA) binding energy (- 114.29 kcal/mol). These findings highlight the therapeutic potential of fumarprotocetraric acid, salazinic acid, and evernic acid, warranting further preclinical investigations to establish their efficacy against cervical cancer.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"114"},"PeriodicalIF":0.0,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823510","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":"Computational studies of natural product compound (CP-225917) for lead identification.","authors":"N S Hari, Ns Hari Narayana Moorthy, Akhilesh Tiwari, Pranay Soni, E Manivannan, C Karthikeyan","doi":"10.1007/s40203-025-00405-6","DOIUrl":"https://doi.org/10.1007/s40203-025-00405-6","url":null,"abstract":"<p><p>In this investigation, a computational analysis of CP-225,917 (a natural product compound isolated from unidentified fungi) on the farnesyl transferase (FTase) enzyme has been performed using docking, PLIF, and molecular dynamics (MD) simulations methodologies to understand its binding interactions. The crystallographic structure of the FTase used for the study was obtained from the Protein Data Bank (PDB id 3E37), and docking, MD simulations, MMPBSA, and PLIF analysis were performed with Autodock 4.2, AMBER 12, and MOE software, respectively. The results showed that the residues such as Lys164, Tyr166, His201, ArgB202, HisB248, TyrB300, LysB356, TyrB361, HisB362, and ZnC1001 have predominantly contributed to the interactions with the molecules through side chain (hydrogen bond acceptor and donor), backbone (hydrogen bond acceptor and donor), surface, and ionic interactions. The aromatic rings in TyrB300 and TyrB361 form surface interactions, and the side chains of all these residues show hydrogen bonding interactions with the molecule. The ionic interaction also formed between the molecules and the residues (LysB356 and Zn²⁺ metal). The MD simulations study revealed that the complex showed significant RMSD and RMSF values below 2.5 Å, confirming that the residues have stabilized the complex. The MM/PBSA analysis also confirms the significant binding affinity of the molecule with the protein. These computational studies concluded that the mode of interactions of CP-225,917 is similar to the other reported compounds on the target and will be a lead compound for the design and development of novel bioactive FTase inhibitors.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00405-6.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"115"},"PeriodicalIF":0.0,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823509","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}