Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Investigating the antimicrobial and antiviral activities of <i>Astragalus spinosus</i> (Forssk.) Muschl.: biological assessments and <i>in silico</i> studies.","authors":"Ahmed A Al-Karmalawy, Yasser A El-Amier, Shaza M Elhusseiny, Haidy A Abbas, Radwan Alnajjar, Mohamed M Khalifa, Faten Farouk, Abdulrahim A Alzain, Rehab F Taher","doi":"10.1080/07391102.2025.2497466","DOIUrl":"https://doi.org/10.1080/07391102.2025.2497466","url":null,"abstract":"<p><p>Herein, the antibacterial, antifungal and antiviral activities of <i>Astragalus spinosus</i> leaves, the largest genus in the family Fabaceae, were evaluated. Forty compounds were identified from the hydroalcoholic plant extract using the LCMS/MS technique. The identified candidates were chemically divided into hydroxycinnamic acid derivatives, flavonoids, and their glycosides. The hydroalcoholic extract showed potent antibacterial activity against <i>Bacillus cereus, Klebsiella pneumoniae</i>, and <i>Pseudomonas aeruginosa</i> with MIC between 5 and 10 mg/mL. Moreover, the extract exhibited a considerable antiviral effect against HSV-2 (IC₅₀ = 57.9 µg/mL). Molecular docking studies were performed to get insights into the different binding poses of the identified candidates toward either the MATE or HSV-1 target receptors. Compounds kaempferol-<i>O</i>-rutinoside and isorhamnetin-<i>O</i>-rutinoside showed superior activity against the MATE receptor, however, isorhamnetin-<i>O</i>-rutinoside and rutin-7-<i>O</i>-hexoside achieved the best binding toward the HSV-1 receptor. The stabilities of the best compounds inside the active pocket were investigated using MD simulation and the MM-GBSA binding energies for the studied complexes were also calculated and compared to the native ligands. Kaempferol-<i>O</i>-rutinoside and isorhamnetin-<i>O</i>-rutinoside showed similar binding energies to the co-crystal ligand of the MATE multidrug efflux pump with MM-GBSA energy of -83.94 and -82.27 kcal/mol, respectively. However, isorhamnetin-<i>O</i>-rutinoside, and rutin-7-<i>O</i>-hexoside showed superiorities over the co-crystal ligands of HSV-1 thymidine kinase by almost 20 and 13 kcal/mol, respectively.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037989","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}

{"title":"Bioinformatics analyses of lignin peroxidases from the smoky bracket fungi <i>Bjerkandera adusta</i> for endocrine disrupting chemical bioremediation.","authors":"Mahfoud Bakli, Khelifa Bouacem, Raul Paşcalău, Laura Șmuleac, Bassem Jaouadi, Haitham Al-Madhagi, Husam Nassar, Abdulrahman H Alessa, Ahmed A Alsaigh","doi":"10.1080/07391102.2025.2498078","DOIUrl":"https://doi.org/10.1080/07391102.2025.2498078","url":null,"abstract":"<p><p>Lignin peroxidases (LiP; EC 1.11.1.14) are important oxidative enzymes involved in lignin biodegradation, a key constituent of plant cell walls. Despite their environmental and industrial potential, fungal LiPs are difficult to express and purify. <i>Bjerkandera adusta</i> is a white-rot fungus that secretes LiPs, the three-dimensional structure of which remains unknown. In this study, two LiPs from <i>B. adusta</i> were subjected to various bioinformatics tools to determine their physio-chemical, structural, and functional properties. Their 3D structure was modeled and molecular dynamic simulations were performed to assess their binding to endocrine disrupting chemicals (EDCs). Moreover, molecular docking analysis revealed that among the model lignin compounds, the dimer guaiacyl 4-O-5 guaiacyl exhibited the lowest binding energy with the EDC ligands, estrone (E1) and bisphenol A showing the strongest binding affinity for LiP 588479560 and LiP 444058, respectively. Molecular dynamics simulations further confirmed the stability of these complexes, with bisphenol A exhibiting particularly high stability as indicated by its low RMSD (≤2 Å) and favorable RoG values, reflecting a strong fit within the enzyme's active site. Additionally, the binding free energy calculations showed the substrate dimer had the most favorable binding energy, driven primarily by Van der Waals and lipophilic interactions, suggesting its intrinsic compatibility with <i>B. adusta</i> LiPs. This in silico characterization advances the understanding of LiP structure-function relationships and bioremediation potential. <i>B. adusta</i> LiPs demonstrate promising capacity to target persistent EDCs, offering solutions for environmental pollution mitigation.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995437","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}

{"title":"Identification of high-affinity inhibitors for epoxide hydrolase 2 from repurposed drugs in Parkinson's disease therapeutics.","authors":"Anas Shamsi, Moyad Shahwan, Sohaib Naseem Khan, Dharmendra Kumar Yadav, Nojood Altwaijry, Asimul Islam, Mohd Shahnawaz Khan","doi":"10.1080/07391102.2025.2497448","DOIUrl":"https://doi.org/10.1080/07391102.2025.2497448","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra that leads to bradykinesia and rest tremors. While the molecular mechanisms underlying PD are not fully understood, rising evidence shows neuroinflammation as a key factor in dopaminergic neuron damage. The soluble epoxide hydrolase (sEH) has appeared as a key player in neuroinflammation associated with PD which represents itself as a promising drug target. Here, we employed a structure-based virtual screening methodology using repurposed drugs from the DrugBank database to identify high-affinity potential inhibitors of sEH. Results showed that two hit molecules, Fluspirilene and Penfluridol, demonstrated appreciable docking potential and specificity toward the sEH active site. These molecules exhibited favorable pharmacological properties and formed critical interactions with residues essential for sEH activity. Further, all-atom molecular dynamics (MD) simulations followed by principal component analysis and free energy landscape were carried out which provide deeper insights into the conformational stability and interaction mechanisms of sEH in complex with Fluspirilene and Penfluridol. The simulation results indicated that the interaction of sEH with Fluspirilene and Penfluridol contributed to the stabilization of its structure throughout the MD trajectories of 500 ns. These findings collectively suggest that Fluspirilene and Penfluridol hold potential as repurposed leads for the development of sEH inhibitors, which offer therapeutic implications for combating PD and other associated conditions.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007365","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}

{"title":"Structure-function studies on drug-reactivating β-glucuronidase from mucin-degrading gut symbiont <i>Akkermansia muciniphila</i>.","authors":"Tarushi, Gagan Deep Gupta, Mukesh Kumar, Subhash C Bihani","doi":"10.1080/07391102.2025.2496291","DOIUrl":"https://doi.org/10.1080/07391102.2025.2496291","url":null,"abstract":"<p><p>Gut microbial β-glucuronidases (mGUS) not only regulate several hormones and neurotransmitters, they also impact the efficacy and toxicity of xenobiotics. On certain anticancer drugs, e.g. irinotecan (SN-38), mGUS activity leads to enterohepatic recirculation resulting into severe diarrhea. Here, we report the expression, purification and characterization of AmGUS, a novel β-glucuronidase from <i>Akkermansia muciniphila. A. muciniphila</i> is a prominent gut symbiont with beneficial effects on metabolic health and gut homeostasis. AmGUS demonstrates specificity towards glucuronide substrates with no glucosidase or galactosidase activity. Interestingly, it also shows efficient cleavage of the glucuronidated form of the anti-cancer drug, SN38, potentially leading to its enterohepatic recirculation. Furthermore, we find that AmGUS functions as a monomer, contrary to other GUS enzymes that exist as oligomers. mGUS are classified into distinct loop-types based on different active site loops around a conserved core providing substrate specificity. Computational modeling of AmGUS structure reveals that it belongs to the mL2 loop-type GUS enzymes, despite sharing significant sequence/structural similarity with the mL1 loop-type and NL-type GUSs. Interestingly, AmGUS also has a unique N-terminal loop previously not observed in any other GUS enzyme possibly aiding in the processing of drug-glucuronides. Together, these findings suggest that GUS from <i>A. muciniphila</i> belongs to a new class of GUS enzymes with unique active site loop structures. The presence of this unique GUS enzyme may help <i>A. muciniphila</i> in colonizing the human gut. Overall, this study broadens our knowledge of the structural and functional understanding of GUSome in the human gut microbiome.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019400","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}

{"title":"Conformational stability and integrity of barley seed β-amylase: evidence of kinetic intermediate in urea-induced unfolding.","authors":"Adejoke N Kolawole, Joshua O Ajele","doi":"10.1080/07391102.2025.2497456","DOIUrl":"https://doi.org/10.1080/07391102.2025.2497456","url":null,"abstract":"<p><p>This research article rates the molecular phenomenon of the barley β-amylase unfolding in the presence of urea and its conformational stability under the influence of selected artificial chaperones (CTAHS, DTAB, CTAB, TTAB, and SHSO₃), with the aim to minimize the enzyme inactivation and aggregation rate in the presence of the chaotropic denaturant (urea). The enzyme was monomeric with a molecular mass of 64.64 kDa. The refolding kinetics was carried out in additive dilution process and artificially mediated chaperone manner. Here, the urea equilibrium unfolding curve assumed a three states conformation of native (N), intermediate (I) and unfolded (U), where the (I) state conformationally have more of secondary and less folded three dimensional structure, a state likened to a β-amylase molten globule conformation. The enzyme has free energy (ΔG) of unfolding of approximately 27 kJmol^-1. These selected chaperones prevented aggregation and stabilized the unfolded intermediates. The cationic artificial chaperones (CTAHS, DTAB, CTAB, and TTAB) observed to be an efficient stabilization of the enzyme against denaturant compared to the anionic chaperon (SHSO₃), characterized with poor refolding kinetics. CTAHS was the most effective chaperone having the percentage (%) refolded structure of 42 ± 2%. Using ANS as hydrophobic probe, β-amylase has a calculated surface hydrophobicity of 204.1 ± 5 and ANS-bound site of 0.29 ± 0.02. These values were compromised after refolding. Taken together, the high intrinsic surface hydrophobicity of β-amylase might be connected to poor recovery rate of the unfolded enzyme.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-10"},"PeriodicalIF":2.7,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036577","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}

{"title":"Evaluation of the structure and stability of myoglobin after interaction with ribose: spectroscopic and molecular simulation approach.","authors":"Rasoul Eslami-Farsani, Sadegh Farhadian, Behzad Shareghi, Sanaz Asgharzadeh, Mahsa Behjati Moghaddam, Lida Momeni, Reza Assaran-Darban, Mina Evini","doi":"10.1080/07391102.2025.2499223","DOIUrl":"https://doi.org/10.1080/07391102.2025.2499223","url":null,"abstract":"<p><p>Osmolytes, as small organic molecules, possess a remarkable ability to exert protective effects on biomacromolecules, including proteins, while preserving their inherent functionality. Myoglobin, a globular protein comprising a sequence of 153 amino acids, fulfills a crucial biological role by exhibiting reversible oxygen binding capabilities and facilitating its efficient transfer to the muscular tissues. In this study, the effects of ribose on myoglobin protein in sodium phosphate buffer were studied by UV-Vis's spectrophotometry and spectrofluorimetric investigations at pH 7.4. Also, the interaction was theoretically studied through molecular dynamics simulation and molecular docking techniques. The results showed that the ribose stabilizes the protein structure by increasing the melting temperature (T_m) of myoglobin. The fluorescence intensity of myoglobin decreased with a static quenching mechanism at different temperatures. The thermodynamic data obtained from the experimental results also predicted that the intermolecular forces affecting the formation of a myoglobin-ribose complex are mainly the van der Waals interactions and hydrogen bindings. Theoretical molecular docking analyses unveiled the favored binding site of ribose within the structure of myoglobin. Subsequent molecular dynamics simulations validated the stability of the complex formed between ribose and myoglobin. Our findings are fundamental for understanding the molecular-level details of myoglobin-ligand interactions, opening avenues for innovative approaches to prevent or alleviate myoglobin dysfunction in various disease conditions.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968697","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}

{"title":"Insights into <i>in silico</i> analysis to explore the multitarget antidepressant role of <i>Camellia sinensis</i>.","authors":"Diksha Choudhary, Rajwinder Kaur, Nidhi Rani, Bhupinder Kumar, Thakur Gurjeet Singh, Balakumar Chandrasekaran, Ravi Rawat, Volkan Eyupoglu","doi":"10.1080/07391102.2025.2498625","DOIUrl":"https://doi.org/10.1080/07391102.2025.2498625","url":null,"abstract":"<p><p>Depression is the fourth leading cause of death due to suicides every year according to WHO. Various adverse effects are associated with many of the available antidepressants due to the irreversible nature of these drugs. So, it is worthwhile to explore the natural phytoconstituents as an alternative therapy for the treatment of depression-dependent symptoms. Computational chemistry provides a cost-effective method to explore or develop new therapies for various diseases through <i>in silico</i> studies. In this study, multitargeting antidepressant potential of <i>Camellia sinensis</i> is explored <i>via</i> docking and binding interaction studies with monoamine oxidase-A enzyme, serotonin, and dopamine receptors involved in depression as targets. All the selected phytoconstituents were evaluated for drug-likeliness properties using Swiss ADME. Among all the selected phytoconstituents, Theasinensin, and Theaflavin-3-gallate were found to have best affinities with all the selected targets under investigation and can be considered as promising lead molecules for the development of novel antidepressants. Molecular dynamics simulations assessed the binding affinity of four compounds to Human Monoamine Oxidase A. All compounds showed potential, with Theaflavin-3-gallate and Theasinesin displaying the strongest binding. This suggests their potential for modulating enzyme activity and potential relevance in depression treatment.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993436","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}

{"title":"Integration analysis of PLAUR as a sunitinib resistance and macrophage related biomarker in ccRCC, an in silicon and experimental study.","authors":"Qiwei Yang, Fangdie Ye, Lin Li, Jian Chu, Yijun Tian, Jianwei Cao, Sishun Gan, Aimin Jiang","doi":"10.1080/07391102.2023.2300754","DOIUrl":"10.1080/07391102.2023.2300754","url":null,"abstract":"<p><p>Sunitinib remains the preferred systemic treatment option for specific patients with advanced RCC who are ineligible for immune therapy. However, it's essential to recognize that Sunitinib fails to elicit a favourable response in all patients. Moreover, most patients eventually develop resistance to Sunitinib. Therefore, identifying new targets associated with Sunitinib resistance is crucial. Utilizing multiple datasets from public cohorts, we conducted an exhaustive analysis and identified a total of 8 microRNAs and 112 mRNAs displaying significant expression differences between Sunitinib responsive and resistant groups. A particular set of six genes, specifically NIPSNAP1, STK40, SDC4, NEU1, TBC1D9, and PLAUR, were identified as highly significant <i>via</i> WGCNA. To delve deeper into the resistance mechanisms, we performed additional investigations using cell, molecular, and flow cytometry tests. These studies confirmed PLAUR's pivotal role in fostering Sunitinib resistance, both <i>in vitro</i> and <i>in vivo</i>. Our findings suggest that PLAUR could be a promising therapeutic target across various cancer types. In conclusion, this investigation not only uncovers vital genes and microRNAs associated with Sunitinib resistance in RCC but also introduces PLAUR as a prospective therapeutic target for diverse cancers. The outcomes contribute to advancing personalized healthcare and developing superior therapeutic strategies.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3956-3973"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087034","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}

{"title":"Monophasic coamorphous sulpiride: a leap in physicochemical attributes and dual inhibition of GlyT1 and P-glycoprotein, supported by experimental and computational insights.","authors":"Ekta Pardhi, Devendra Singh Tomar, Rahul Khemchandani, Mohd Rabi Bazaz, Manoj P Dandekar, Gananadhamu Samanthula, Shashi Bala Singh, Neelesh Kumar Mehra","doi":"10.1080/07391102.2024.2308048","DOIUrl":"10.1080/07391102.2024.2308048","url":null,"abstract":"<p><p>Study aimed to design and development of a supramolecular formulation of sulpiride (SUL) to enhance its solubility, dissolution and permeability by targeting a novel GlyT1 inhibition mechanism. SUL is commonly used to treat gastric and duodenal ulcers, migraine, anti-emetic, anti-depressive and anti-dyspeptic conditions. Additionally, Naringin (NARI) was incorporated as a co-former to enhance the drug's intestinal permeability by targeting P-glycoprotein (P-gp) efflux inhibition. NARI, a flavonoid has diverse biological activities, including anti-apoptotic, anti-oxidant, and anti-inflammatory properties. This study aims to design and develop a supramolecular formulation of SUL with NARI to enhance its solubility, dissolution, and permeability by targeting a novel GlyT1 inhibition mechanism, extensive experimental characterization was performed using solid-state experimental techniques in conjunction with a computational approach. This approach included quantum mechanics-based molecular dynamics (MD) simulation and density functional theory (DFT) studies to investigate intermolecular interactions, phase transformation and various electronic structure-based properties. The findings of the miscibility study, radial distribution function (RDF) analysis, quantitative simulations of hydrogen/π-π bond interactions and geometry optimization aided in comprehending the coamorphization aspects of SUL-NARI Supramolecular systems. Molecular docking and MD simulation were performed for detailed binding affinity assessment and target validation. The solubility, dissolution and <i>ex-vivo</i> permeability studies demonstrated significant improvements with 31.88-fold, 9.13-fold and 1.83-fold increments, respectively. Furthermore, biological assessments revealed superior neuroprotective effects in the SUL-NARI coamorphous system compared to pure SUL. In conclusion, this study highlights the advantages of a drug-nutraceutical supramolecular formulation for improving the solubility and permeability of SUL, targeting novel schizophrenia treatment approaches through combined computational and experimental analyses.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4297-4326"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650829","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}

{"title":"Investigation of the interaction between S-isoalkyl derivatives of the thiosalicylic acid and human serum albumin.","authors":"Marina Vesović, Ratomir Jelić, Miloš Nikolić, Nikola Nedeljković, Ana Živanović, Andriana Bukonjić, Emina Mrkalić, Gordana Radić, Zoran Ratković, Jakob Kljun, Dušan Tomović","doi":"10.1080/07391102.2024.2301745","DOIUrl":"10.1080/07391102.2024.2301745","url":null,"abstract":"<p><p>S-isoalkyl derivatives of thiosalicylic acid (isopropyl-(L1), isobutyl-(L2) and isoamyl-(L3)) were selected in order to investigate the binding interaction with the human serum albumin (HSA) using different spectroscopic methods and molecular docking simulation. Association constants and number of binding sites were used to analyze the quenching mechanism. The experimental results showed that the fluorescence quenching of HSA by L1, L2 and L3 occurs because of static quenching and that binding processes were spontaneous, with the leading forces in bonding by hydrogen bonding, hydrophobic interactions, and electrostatic interactions. Fluorescence spectroscopy, UV-Vis spectroscopy and synchronous fluorescence spectroscopy showed that ligands (L1, L2 and L3) can bind to HSA and that the binding of ligands induced some microenvironmental and conformational changes in HSA. The calculated distance between the donor and the acceptor according to fiFörster's theory confirms the energy transfer efficiency between the acceptor and HSA. Results of site marker competitive experiments showed that the tested compounds bind to HSA in domain IIA (Site I). Molecular dynamics and docking calculations demonstrated that L3 binds to the Sudlow site I of HSA with lower values of binding energies compared to L1 and L2, indicating the formation of the most stable ligand-HSA complex. Understanding the binding mechanisms of S-isoalkyl derivatives of the thiosalicylic acid to HSA may provide valuable data for the future studies of their biological activity and application as potential antitumor drugs.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4081-4094"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403046","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}