Journal of Biomolecular Structure & Dynamics最新文献_第7页

Immunoinformatics-driven approach for development of potential multi-epitope vaccine against the secreted protein FlaC of Campylobacter jejuni. 针对空肠弯曲杆菌分泌蛋白 FlaC 开发潜在多位点疫苗的免疫信息学驱动方法。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-07-01 Epub Date: 2024-01-29 DOI: 10.1080/07391102.2024.2308766

Deepak Saravanan, Monisha Mohan

{"title":"Immunoinformatics-driven approach for development of potential multi-epitope vaccine against the secreted protein FlaC of Campylobacter jejuni.","authors":"Deepak Saravanan, Monisha Mohan","doi":"10.1080/07391102.2024.2308766","DOIUrl":"10.1080/07391102.2024.2308766","url":null,"abstract":"Campylobacter jejuni causes a leading human gastrointestinal infection which is associated with foodborne diarrhea, stomach cramping, and fever. In the recent years, numerous multidrug-resistant strains of C. jejuni has evolved and is considered in the priority pathogens category. Therefore, an increasing demand exists to develop an effective vaccine against Campylobacteriosis. The T cell and B cell epitopes from the FlaC protein were predicted using comprehensive immunoinformatics tools. The predicted epitopes were chosen based on their antigenicity, allergenicity, and toxicity profiles. Using the bioinformatics approach various physicochemical properties of the constructed vaccine were determined. The molecular docking analysis of the vaccine with the TLRs demonstrated that TLR5 has a higher binding affinity of -1159.0 kcal/mol. Molecular dynamics simulation has confirmed the stable association of the vaccine with TLR5. The immune response of the constructed vaccine was validated using immunostimulation. Based on this study, we recommend the formulation of a multi-epitope vaccine as a promising agent to effectively combat the dreadful campylobacteriosis infection.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5331-5342"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Using integrated bioinformatics, network pharmacology and molecular docking to explore the mechanisms underlying the antidepressant effect of celastrol. 结合生物信息学、网络药理学和分子对接等方法，探讨雷公藤红素抗抑郁作用的机制。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-30 DOI: 10.1080/07391102.2025.2520568

Yong-Li Jiang, Xin-Shang Wang, Fei-Yan Wang, Mei-Ling Zheng, Le Yang, Yu-Chen Jin, Ying Gao, Qing-Juan Guo, Da-Ke Song, Li Luo, Shui-Bing Liu

{"title":"Using integrated bioinformatics, network pharmacology and molecular docking to explore the mechanisms underlying the antidepressant effect of celastrol.","authors":"Yong-Li Jiang, Xin-Shang Wang, Fei-Yan Wang, Mei-Ling Zheng, Le Yang, Yu-Chen Jin, Ying Gao, Qing-Juan Guo, Da-Ke Song, Li Luo, Shui-Bing Liu","doi":"10.1080/07391102.2025.2520568","DOIUrl":"https://doi.org/10.1080/07391102.2025.2520568","url":null,"abstract":"Celastrol, a natural compound derived from the root of Tripterygium wilfordii Hook. F., has shown potential efficacy in alleviating depression in animal models, yet its specific target remains unelucidated. The present investigation aimed to identify the principal targets and possible signaling pathways of celastrol in major depressive disorder (MDD). Using a combination of GEO datasets, network pharmacology, molecular docking and molecular dynamics simulation techniques, we conducted an analysis to uncover the underlying mechanism through which celastrol exerts its antidepressant effects. Our analysis identified a total of 1064 drug targets and 3386 disease-related targets, resulting in 209 shared targets. A topological examination of the protein-protein interaction (PPI) network revealed 10 core targets, including STAT3, IL6, ALB, HSP90AA1, HIF1A, CASP3, EGFR, BCL2L1, INS and IGF1. GO and KEGG pathway enrichment analyses demonstrated that celastrol exerted antidepressant effects through regulating genes related to inflammation, apoptosis, oxidative stress and the PI3K/Akt, MAPK, and HIF1 signaling pathways. Furthermore, the results of molecular docking and molecular dynamics simulations revealed the strong binding affinity between celastrol and HIF1A. In conclusion, this study effectively predicted the possible molecular targets and signaling pathways of celastrol in the treatment of depression, providing a promising approach for future investigations into its mechanisms against MDD.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modeling of phosphorylated forms of complement system factors C4 and CFB. 补体系统因子C4和CFB磷酸化形式的建模。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-30 DOI: 10.1080/07391102.2025.2524410

Kirill Sergeevich Nikolsky, Denis Vitalievich Petrovskiy, Liudmila Ivanovna Kulikova, Vladimir Removich Rudnev, Tatiana Vladimirovna Butkova, Natalia Valerievna Potoldykova, Dmitry Viktorovich Enikeev, Kristina Akhmedovna Malsagova, Arthur Tigranovich Kopylov, Valeria Igorevna Nakhod, Alexander Anatolievich Izotov, Anna Leonidovna Kaysheva

{"title":"Modeling of phosphorylated forms of complement system factors C4 and CFB.","authors":"Kirill Sergeevich Nikolsky, Denis Vitalievich Petrovskiy, Liudmila Ivanovna Kulikova, Vladimir Removich Rudnev, Tatiana Vladimirovna Butkova, Natalia Valerievna Potoldykova, Dmitry Viktorovich Enikeev, Kristina Akhmedovna Malsagova, Arthur Tigranovich Kopylov, Valeria Igorevna Nakhod, Alexander Anatolievich Izotov, Anna Leonidovna Kaysheva","doi":"10.1080/07391102.2025.2524410","DOIUrl":"https://doi.org/10.1080/07391102.2025.2524410","url":null,"abstract":"Kidney cancer ranks as the 14th most common cancer worldwide. Despite its heterogeneity, it often presents with clinical manifestations similar to other renal diseases, which complicates timely diagnosis. Many types of malignant renal neoplasms can mimic benign processes, and some tumors can develop asymptomatically until the late stages of the disease. Our research focuses on modeling complement C4 and CFB proteoforms, which are of interest for understanding the molecular basis of pathogenesis for common kidney diseases: kidney calculi, kidney cysts, and malignant neoplasms of the kidney. In this work, we performed an analysis of the stability and interface characterization of these proteins in complexes with their natural binding partners using molecular dynamics methods. We have demonstrated that the phosphorylation sites of complement factors C4 125TPO and CFB 161SEP are localized at the binding interface with their natural partners. This modification likely modulates protein function, as we have identified local effects in the vicinity of the modification site. In protein complexes, we observe a redistribution of energetic contributions among the interacting amino acid residues at the interface.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elucidating the role of genome in geminiviral capsid dynamics. 阐明基因组在双病毒衣壳动力学中的作用。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-29 DOI: 10.1080/07391102.2025.2524408

Yagavi Ravindran, Kothai Thiruvengadam, Lakshmi S Baddireddi, Sangita Venkataraman

{"title":"Elucidating the role of genome in geminiviral capsid dynamics.","authors":"Yagavi Ravindran, Kothai Thiruvengadam, Lakshmi S Baddireddi, Sangita Venkataraman","doi":"10.1080/07391102.2025.2524408","DOIUrl":"https://doi.org/10.1080/07391102.2025.2524408","url":null,"abstract":"Geminiviridae is the largest group of single-stranded (ss) DNA viruses, infecting a wide range of plant species and posing a significant threat to agriculture. Hence, we used molecular dynamics simulations to explore the structural impacts and the stability of Ageratum yellow vein virus (AYVV) capsids in the presence and absence of DNA. The findings show that dimers, trimers, pentamers, and higher multimers are remarkably stable when bound to DNA during the course of the 300 ns simulation. On the contrary, the oligomers demonstrate significant instability and disintegration in the absence of DNA. While DNA-free oligomers retained structural integrity, the quaternary association broke down, particularly in pentameric and dimeric units. While previous experimental studies have demonstrated the stability of geminiviral pentamers, our observations suggest that their resilience is likely linked to their association with DNA. Remarkably, the dimers lacking the bound DNA also display an atypical variation in curvature over time. Consequently, we propose that any trigger that loosens the association of the genome with the oligomers would be a prerequisite for the intersubunit contacts in the capsid to break and release the genome. We hypothesize that genomic DNA may interact with the pentamers to initiate capsid assembly, which may pave the way for the dimers and trimers to be integrated. The natural flexibility of the dimers could render it easier to provide the appropriate curvature and closure to the swiftly forming capsid. Thus, techniques that target DNA-protein interactions in geminiviruses could be the key to their effective management in fields.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-8"},"PeriodicalIF":2.7,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-29 DOI: 10.1080/07391102.2025.2524406

Lilia V Fedulova, Mikhail I Drobotenko, Anna A Dorohova, Ekaterina R Vasilevskaya, Alexandr A Svidlov, Irina M Chernukha, Stepan S Dzhimak

引用次数: 0

Spectroscopic and computer science insights from the binding of palbociclib with bovine serum albumin. 帕博西尼与牛血清白蛋白结合的光谱和计算机科学见解。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-26 DOI: 10.1080/07391102.2025.2517393

Huan-Yu Sui, Zhe-Ying Hu, Li Li, Jie-Hua Shi, Shao-Liang Jiang

{"title":"Spectroscopic and computer science insights from the binding of palbociclib with bovine serum albumin.","authors":"Huan-Yu Sui, Zhe-Ying Hu, Li Li, Jie-Hua Shi, Shao-Liang Jiang","doi":"10.1080/07391102.2025.2517393","DOIUrl":"https://doi.org/10.1080/07391102.2025.2517393","url":null,"abstract":"Spectroscopic and molecular simulation techniques are increasingly becoming powerful tools for studying the drug-protein binding acting. In this article, the conjugation features of palbociclib, a cell cycle-dependent kinase 4/6 (CDK4/6) inhibitor primarily used for HR+/HER2- breast cancer treatment, with bovine serum albumin (BSA) was examined in a physiomimetic setting. Based on the experimental results, the incorporation of a 1:1 palbociclib-BSA complex resulted in the intrinsic fluorescence quenching of BSA by palbociclib via static quenching. The results of competition experiments suggested that palbociclib has a higher probability for entering the BSA target Site III as compared to site I and site II. The thermodynamic and competition experiments yielded evidence to suggest that van der Waals forces, hydrogen bonding and hydrophobic interactions were responsible for the binding of palbociclib to BSA. Structural alterations resulting from palbociclib administration to BSA illustrated a minor influence of palbociclib on the advanced conformations of BSA. However, it led to an increase in hydrophobicity surrounding the tryptophan (Trp) and tyrosine (Tyr) residues. In addition, the experimental findings underwent a validation via the application of molecular docking and molecular dynamics simulations.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural and antigenic variation in Hepatitis B virus oncogene, HBx. 乙型肝炎病毒致癌基因HBx的结构和抗原变异。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-16 DOI: 10.1080/07391102.2025.2517826

Fatima Fasih, Nusrat Jabeen, Mushtaq Hussain, Atiya Habib, Shaheen Sharafat, Zaheer Ul-Haq

{"title":"Structural and antigenic variation in Hepatitis B virus oncogene, HBx.","authors":"Fatima Fasih, Nusrat Jabeen, Mushtaq Hussain, Atiya Habib, Shaheen Sharafat, Zaheer Ul-Haq","doi":"10.1080/07391102.2025.2517826","DOIUrl":"https://doi.org/10.1080/07391102.2025.2517826","url":null,"abstract":"Hepatitis B Virus (HBV) is a known oncogenic virus, with over 50% of infections leading to hepatocellular carcinoma. The virus's primary oncogenic protein is identified as HBx. Over the past decade, only a limited number of studies have explored the structure of HBx using computational approaches. Depending on the method used, two significantly different topologies with notable variations in secondary structure elements have been predicted for this protein. In this study, we compare both predicted structural configurations of HBx and extend our analysis across different genotypes and strains of both human and non-human HBV. Phylogenetic analysis of HBx suggests zoonotic transmission of the virus between humans and orangutan HBV. Several critical residues essential for HBV transcription, including Cys61, Cys69, Cys137, and His139, are conserved across all mammalian HBV, including human strains. In contrast, residues such as Ser25 (involved in intranuclear localization of HBx), Pro90 (associated with UVDBB interaction), and Cys115 (linked to mitochondrial localization of HBx) are exclusive to human HBV, indicating potential sub-neofunctionalization of the HBx protein in human strains. Molecular models of HBx generated using I-TASSER and AlphaFold were non-superimposable. Structural alignment with a partially resolved HBx structure, along with molecular dynamics (MD) simulations, supports the prediction made by AlphaFold. Additionally, AlphaFold predicted HBx structure exhibits similarity to palmitoleoyl transferases, suggesting a possible evolutionary origin. This study provides valuable insights into the origin and evolutionary development of the oncogenic potential of HBx in mammalian HBV.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In silico identification and characterization of potential allergenic proteins from Vigna mungo (blackgram). 芒果葡萄中潜在致敏蛋白的计算机鉴定和表征。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-16 DOI: 10.1080/07391102.2025.2512177

Archana Singh, Shradheya R R Gupta, Kalpesh Nath Yajnik, Saumya Dubey, Indrakant K Singh

{"title":"In silico identification and characterization of potential allergenic proteins from Vigna mungo (blackgram).","authors":"Archana Singh, Shradheya R R Gupta, Kalpesh Nath Yajnik, Saumya Dubey, Indrakant K Singh","doi":"10.1080/07391102.2025.2512177","DOIUrl":"https://doi.org/10.1080/07391102.2025.2512177","url":null,"abstract":"It is concerning that allergic symptoms related to consuming black gram or Vigna mungo-based diets have been reported from Asia and Australia. Since the identification of specific allergenic proteins from blackgram is in its infancy, it demands further exploration and underscores the complexity of food allergies. To decipher allergenic proteins from V. mungo and to characterize them, an in-silico study was conducted. Out of the total proteins available on UniProt, the potential allergens, vignain (P12412), peptide-prolyl cis-trans isomerase (D3VMM4), and cysteine protease (Q9MB27) were selected for further analysis based on their allergenic potential. Their antigen binding sites were predicted and 3D structures were modeled and docked with immunoglobin IgE and T cell antibody and their binding energies were obtained. To find the stability of the interactions, MD simulations were conducted and the results indicated that Q9MB27, D3VMM4 and P12412 formed stable bonds with IgE and T cell antibodies. Identifying the specific proteins responsible for these allergic reactions could be crucial for developing effective diagnostic tools and potential therapies to help individuals manage their allergies more efficiently. Further validation of the above results by in vitro and in vivo methods is highly recommended.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-22"},"PeriodicalIF":2.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the potential of lichen compounds hyaluronic acid conjugates for cervical cancer treatment: a comprehensive in silico analysis. 揭示地衣化合物透明质酸偶联物治疗宫颈癌的潜力：全面的硅分析。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-14 DOI: 10.1080/07391102.2025.2516134

M Gomathi, P Nandu Baby, K Saranya, Arunachalalm Chinnathambi, Sulaiman Ali Alharbi, Jeyakumar Saranya Packialakshmi

{"title":"Unveiling the potential of lichen compounds hyaluronic acid conjugates for cervical cancer treatment: a comprehensive in silico analysis.","authors":"M Gomathi, P Nandu Baby, K Saranya, Arunachalalm Chinnathambi, Sulaiman Ali Alharbi, Jeyakumar Saranya Packialakshmi","doi":"10.1080/07391102.2025.2516134","DOIUrl":"https://doi.org/10.1080/07391102.2025.2516134","url":null,"abstract":"The current study investigated five lichen-derived compounds and their hyaluronic acid (HA) conjugates for activity against five key cervical cancer targets. The lichen compounds and the reference drug topotecan exhibited docking scores ranging from -5.5 to -10.1 kcal/mol and -6.4 to -8.5 kcal/mol, respectively. Notably, the HA-evernic acid conjugate demonstrated the strongest binding to BCL-2 (-10.1 kcal/mol), forming two hydrogen bonds (Ala97, Glu133) and four hydrophobic interactions (Asp100, Arg143, Val145, Tyr199). Similarly, the HA-salazinic acid conjugate displayed high affinity for histone deacetylase 6 (HDAC6; -9.9 kcal/mol). The top-performing compounds, fumarprotocetraric acid, salazinic acid, topotecan, and their HA conjugates, were advanced to computational validation. Pharmacokinetic analysis revealed that HA-salazinic acid (HA-SAL) possessed optimal ADMET properties, including 71.39% human intestinal absorption, no inhibition of cytochrome P450 enzymes or P-glycoprotein, and low toxicity in cardiac (hERG), hepatic, and aquatic models. Density functional theory (DFT) calculations highlighted the HA conjugates of fumarprotocetraric acid (HA-FUM) and salazinic acid as superior to topotecan, with HA-FUM showing the lowest energy gap (-0.1038 eV) and highest softness (19.2678 eV), indicative of enhanced reactivity. Molecular dynamics simulations further validated the stability of HA-salazinic acid-HDAC6 (PDB ID 3PHD) and HA-evernic acid-BCL-2 (PDB ID 4MAN) complexes, outperforming the standard drug hyaluronic acid conjugate. These results underscore the potential of lichen compound-HA conjugates, particularly fumarprotocetraric acid, salazinic acid, and evernic acid, as candidates for cervical cancer therapy. Further preclinical and clinical studies are warranted to evaluate their efficacy and safety for translational applications.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Revisiting Plasmodium falciparum P-type ATPase 4 in malarial: ADMET, mutation effect, and molecular simulation studies of potential inhibitors. 疟疾中的恶性疟原虫p型atp酶4:ADMET、突变效应和潜在抑制剂的分子模拟研究。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-13 DOI: 10.1080/07391102.2025.2516757

Iseoluwa Isaac Ajayi, Toluwase Hezekiah Fatoki, Ayodele Sunday Alonge, Courage Dele Famusiwa, Ibrahim Olabayode Saliu, Blessing Anuoluwapo Ejimadu, Mayowa Oluwalana Obafemi

{"title":"Revisiting Plasmodium falciparum P-type ATPase 4 in malarial: ADMET, mutation effect, and molecular simulation studies of potential inhibitors.","authors":"Iseoluwa Isaac Ajayi, Toluwase Hezekiah Fatoki, Ayodele Sunday Alonge, Courage Dele Famusiwa, Ibrahim Olabayode Saliu, Blessing Anuoluwapo Ejimadu, Mayowa Oluwalana Obafemi","doi":"10.1080/07391102.2025.2516757","DOIUrl":"https://doi.org/10.1080/07391102.2025.2516757","url":null,"abstract":"Malaria, a life-threatening disease caused by Plasmodium parasites, remains a major global health concern, with 247 million cases and approximately 627,000 deaths reported in 2020 across 84 malaria-endemic countries. The Plasmodium falciparum P-type ATPase 4 (PfATP4) gene is expressed throughout the parasite's asexual erythrocytic cycle and plays a vital role in regulating sodium ion levels in the plasma membrane. This study aimed to computationally evaluate selected clinical candidate compounds targeting PfATP4, focusing on their pharmacokinetics and molecular binding characteristics to support further drug development. Pharmacokinetic analyses revealed that Concanamycin A, Maduramicin, and GNF-Pf4492 exhibit low gastrointestinal absorption, while Brefeldin A, MMV396719, MMV006239, and Cipargamin can cross the blood-brain barrier. Among these, Brefeldin A and MMV006239 showed the lowest toxicity. Molecular docking revealed that (+)-SJ733 had the highest binding affinity (-8.891 kcal/mol), followed by MMV665878 (-7.796 kcal/mol) and Maduramicin (-7.791 kcal/mol). All 11 compounds showed binding affinities below -7.000 kcal/mol. Molecular dynamics simulations indicated stable interactions between PfATP4 and both (+)-SJ733 and MMV665878, involving key residues such as PHE917, GLN921, ARG985, and THR993. MMGBSA analysis showed that the MMV665878-PfATP4 complex was more stable and energetically favorable than the (+)-SJ733-PfATP4 complex under simulated physiological conditions. In conclusion, (+)-SJ733 and MMV665878 demonstrate strong potential as PfATP4 inhibitors, with different interaction profiles. Further in vivo and pharmacometric studies are required to validate their efficacy and determine optimal dosing strategies for malaria treatment.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0