Emadeldin M. Kamel, Doaa A. Abdelrheem, Faris F. Aba Alkhayl, Fahad M. Alshabrmi, May Bin-Jumah, Abdullah S. Alawam, Al Mokhtar Lamsabhi
{"title":"Coumarin-Based Allosteric Inhibition of PTP1B: A Potential Strategy for Metabolic Regulation","authors":"Emadeldin M. Kamel, Doaa A. Abdelrheem, Faris F. Aba Alkhayl, Fahad M. Alshabrmi, May Bin-Jumah, Abdullah S. Alawam, Al Mokhtar Lamsabhi","doi":"10.1002/jmr.70006","DOIUrl":"https://doi.org/10.1002/jmr.70006","url":null,"abstract":"<div>\u0000 \u0000 <p>Protein Tyrosine Phosphatase 1B (PTP1B) is a key metabolic regulator and a promising therapeutic target for type 2 diabetes and obesity. This study evaluated the inhibitory potential of four coumarins—Bergapten, Imperatorin, Xanthotoxol, and Isopimpinellin, isolated from <i>Ammi majus</i>—through <i>in silico</i> and in vitro approaches. Molecular docking and molecular dynamics (MD) simulations identified Bergapten and Imperatorin as the most stable binders, forming key π–π stacking interactions with Phe280 and Phe196. Principal Energy Landscape (PEL) analysis further confirmed their stable binding conformations, while MM/PBSA calculations ranked Bergapten (−17.21 ± 0.80 kcal/mol) and Imperatorin (−12.76 ± 2.99 kcal/mol) as the strongest binders. ADMET analysis indicated high gastrointestinal absorption, blood–brain barrier permeability, and favorable drug-like properties for all compounds. In vitro PTP1B inhibition assays validated these findings, with Bergapten (IC<sub>50</sub> = 6.64 ± 0.23 μM) and Imperatorin (IC<sub>50</sub> = 9.44 ± 1.05 μM) exhibiting potent inhibition, comparable to the reference inhibitor ursolic acid (IC<sub>50</sub> = 7.43 ± 0.74 μM), whereas Xanthotoxol (IC<sub>50</sub> = 28.60 ± 1.88 μM) and Isopimpinellin (IC<sub>50</sub> = 25.48 ± 1.98 μM) showed significantly weaker inhibition. Enzyme kinetics revealed noncompetitive inhibition mechanisms, with <i>K</i><sub>i</sub> values of 6.73 μM and 8.44 μM for Bergapten and Imperatorin, respectively, suggesting allosteric binding. These results highlight Bergapten and Imperatorin as promising allosteric inhibitors of PTP1B, warranting further cell-based and preclinical investigations for potential therapeutic applications in metabolic disorders.</p>\u0000 </div>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"38 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuewen Cai, Lu Zheng, Erdeng Du, Rui Ma, Jun Chen, Yao Wu, Jiayao Li, Xichen Wang, Mingguo Peng
{"title":"Multispectral Analysis and Molecular Simulation of the Interactions Between Perfluorodecanoic Acid/Perfluorosebacic Acid and Human Serum Albumin","authors":"Xuewen Cai, Lu Zheng, Erdeng Du, Rui Ma, Jun Chen, Yao Wu, Jiayao Li, Xichen Wang, Mingguo Peng","doi":"10.1002/jmr.70008","DOIUrl":"https://doi.org/10.1002/jmr.70008","url":null,"abstract":"<div>\u0000 \u0000 <p>Per- and polyfluoroalkyl substances (PFASs) have raised significant environmental and health concerns due to their persistence and toxicity. The study employed a comprehensive analytical approach to clarify the interaction mechanisms between perfluorodecanoic acid (PFDA) and perfluorosebacic acid (PFSEA) with human serum albumin (HSA). The results indicated that PFDA/PFSEA quench HSA's intrinsic fluorescence through static quenching. At 298 K, PFDA demonstrated a more pronounced effect, with a higher binding constant of 9.14 × 10<sup>5</sup> mol/L, surpassing PFSEA's constant of 7.65 × 10<sup>4</sup> mol/L. Thermodynamic analysis revealed that hydrogen bonding was the predominant force in the HSA-PFDA/PFSEA interaction, and the binding processes were exothermic and spontaneous. Quantum chemical structure analysis underscored the heightened reactivity at the carbonyl groups of PFDA and PFSEA. Molecular docking and competitive binding experiments confirmed that PFDA/PFSEA bind to HSA's IIA subdomain, inducing alterations in HSA's secondary structure and amino acid residue's microenvironment. The HSA-PFDA complex exhibited a lower binding free energy (−15.91 kcal/mol) than the HSA-PFSEA complex (−11.06 kcal/mol), indicating a stronger binding affinity. This study elucidated the interactions of PFDA and PFSEA with biological macromolecules, revealing their bioactivity and informing their biosafety and environmental risk assessment.</p>\u0000 </div>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"38 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144536834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nasser Abdulatif Al-Shabib, Javed Masood Khan, Ajamaluddin Malik, Abdulaziz Alamri, Abdullah S. Alhomida, Fohad Mabood Husain
{"title":"Food Additive Hexametaphosphate Promotes Amyloid Formation in Human Serum Albumin: A Molecular Insight","authors":"Nasser Abdulatif Al-Shabib, Javed Masood Khan, Ajamaluddin Malik, Abdulaziz Alamri, Abdullah S. Alhomida, Fohad Mabood Husain","doi":"10.1002/jmr.70007","DOIUrl":"https://doi.org/10.1002/jmr.70007","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigates the aggregation behavior of human serum albumin (HSA) in its cationic (pH 2.0) and anionic (pH 8.0) states upon exposure to hexametaphosphate (HMP), a polyanionic compound. UV–Vis turbidity measurements revealed that cationic HSA aggregated in a concentration-dependent manner starting at 0.01 mM HMP and plateaued beyond 0.05 mM, while anionic HSA remained soluble even at 15 mM HMP. Intrinsic fluorescence analysis showed a blue shift in the emission maximum of cationic HSA, indicating conformational changes associated with aggregation, whereas no shift was observed in anionic HSA. Far-UV circular dichroism (CD) spectroscopy demonstrated that cationic HSA lost its alpha-helical structure and adopted cross-beta sheet conformations at HMP concentrations ≥ 0.05 mM, consistent with amyloid formation, which was further supported by increased Thioflavin T (ThT) fluorescence. Rayleigh light scattering (RLS) and ThT kinetic studies confirmed rapid, saturation-limited aggregation without a lag phase. Transmission electron microscopy (TEM) further verified the presence of amyloid-like fibrils in cationic HSA treated with HMP. In contrast, anionic HSA showed no structural or aggregation changes under identical conditions. These findings highlight the pH-dependent, amyloidogenic potential of HSA in the presence of HMP and underscore the role of electrostatic interactions in protein aggregation.</p>\u0000 </div>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"38 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aaliya Taiyab, Md Nayab Sulaimani, Aanchal Rathi, Fazlurrahman Khan, Afzal Hussain, Mohamed F. Alajmi, Md. Imtaiyaz Hassan
{"title":"Repurposing FDA-Approved Drugs to Target MTH1 for Anticancer Therapeutics","authors":"Aaliya Taiyab, Md Nayab Sulaimani, Aanchal Rathi, Fazlurrahman Khan, Afzal Hussain, Mohamed F. Alajmi, Md. Imtaiyaz Hassan","doi":"10.1002/jmr.70005","DOIUrl":"https://doi.org/10.1002/jmr.70005","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer cells exhibit elevated levels of reactive oxygen species, resulting in oxidative stress and DNA damage. To counteract this, many cancers upregulate the expression of MTH1 (MutT Homolog-1), a crucial enzyme that detoxifies oxidised nucleotide pools. Consequently, inhibiting MTH1 is a potential therapeutic strategy for managing DNA damage and cancer cell death. Here, we conducted a comprehensive computational screening of 3800 FDA-approved drugs to identify potential MTH1 inhibitors. Among these, Lumacaftor and Nilotinib were selected based on their strong binding affinity and pharmacokinetic profiles. Molecular dynamics simulations over 500 ns further validated the stable binding of these drugs to MTH1, suggesting their potential as effective inhibitors. Nilotinib, a well-known tyrosine kinase inhibitor (TKI), displayed strong binding affinity (<i>K</i>a = 2.5 × 10<sup>4</sup>) and potent MTH1 inhibitory activity (IC<sub>50</sub>: 37.2 μM). Notably, this study is the first to establish the interaction between Nilotinib and MTH1, highlighting the dual potential of Nilotinib as an MTH1 inhibitor. The findings suggest that Nilotinib could be repurposed to enhance cancer therapy, particularly in combating drug resistance through the novel mechanism of MTH1 inhibition. This approach provides new avenues for tackling chemoresistance and improving therapeutic outcomes in cancer patients.</p>\u0000 </div>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"38 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Feiyan Yan, Yan Wang, Lin Chen, Wei Cheng, Ernest Oduro-Kwateng, Mahmoud E. S. Soliman, Ting Yang
{"title":"Nanohydrogel of Curcumin/Berberine Co-Crystals Induces Apoptosis via Dual Covalent/Noncovalent Inhibition of Caspases in Endometrial Cancer Cell Lines: The Synergy Between Pharmacokinetics and Pharmacodynamics","authors":"Feiyan Yan, Yan Wang, Lin Chen, Wei Cheng, Ernest Oduro-Kwateng, Mahmoud E. S. Soliman, Ting Yang","doi":"10.1002/jmr.70004","DOIUrl":"https://doi.org/10.1002/jmr.70004","url":null,"abstract":"<p>Endometrial cancer remains a significant therapeutic challenge due to drug resistance and heterogeneity. This study leverages the synergistic potential of curcumin (CUR) and berberine (BBR) co-crystals encapsulated in a nanohydrogel to address these challenges through a pharmacokinetically and pharmacodynamically targeted therapeutic strategy. The nanohydrogel formulation significantly improves the solubility, stability, and bioavailability of CUR/BBR co-crystals, optimizing their therapeutic delivery and sustained release under physiological and tumor microenvironment conditions. On the other hand, the dual inhibitory mechanism of CUR and BBR, with CUR covalently binding to the active site of caspase-3 and BBR non-covalently targeting the allosteric site, achieves enhanced apoptotic activity by disrupting both the catalytic and conformational functions of caspase-3. In vitro cytotoxicity assays demonstrate remarkable efficacy of the CUR/BBR nanohydrogel, achieving an IC50 of 12.36 μg/mL against HEC-59 endometrial cancer cells, significantly outperforming the individual components and the standard drug Camptothecin (IC50: 17.27 μg/mL). Caspase-3/7 assays confirm enhanced apoptosis induction for the nanohydrogel formulation compared to co-crystals alone and Camptothecin. Molecular dynamics simulations and binding free energy analyses further validate the synergistic interaction of CUR and BBR in their dual binding mode. This study introduces a novel therapeutic approach by enhancing drug delivery and dual targeting mechanisms, demonstrating the potential of CUR-BBR nanohydrogel as a robust therapy for EC. This strategy offers a promising platform for addressing drug resistance and improving outcomes in endometrial cancer therapy.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"38 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmr.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Semen V. Nesterov, Nikolay S. Ilyinsky, Alexander V. Fonin, Vladimir N. Uversky
{"title":"Signal Transduction by Phase Separation—Unnoticed Revolution in Molecular Biology","authors":"Semen V. Nesterov, Nikolay S. Ilyinsky, Alexander V. Fonin, Vladimir N. Uversky","doi":"10.1002/jmr.70003","DOIUrl":"https://doi.org/10.1002/jmr.70003","url":null,"abstract":"<div>\u0000 \u0000 <p>Recent scientific findings highlight the crucial role of liquid-liquid phase separation (LLPS) in the compartmentalization of enzyme systems. A synthesis of the extant data indicates that lipid rafts and condensates formed by phase separation are also implicated in signal transduction, including participation in recognized receptor systems. The intrinsically disordered nature of many membrane-binding proteins, coupled with their propensity for LLPS, provides condensate formation, which can bind to or form on the membranes. Moreover, condensates can form simultaneously on both sides of the membrane at lipid raft regions facilitating signal transmission across the membrane. The finding that LLPS plays a direct role in cell signaling, especially in well-defined transmembrane signaling pathways, represents a substantial, yet largely unrecognized, advancement in understanding of intracellular signal transduction mechanisms.</p>\u0000 </div>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"38 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matheus de Oliveira Silva Pinto, Leonardo de Paula Pereira, Ana Luiza Pessoa de Mendonça Angelo, Marcelo Antônio Pascoal Xavier, Alexandre de Magalhães Vieira Machado, Remo Castro Russo
{"title":"Dissecting the COVID-19 Immune Response: Unraveling the Pathways of Innate Sensing and Response to SARS-CoV-2 Structural Proteins","authors":"Matheus de Oliveira Silva Pinto, Leonardo de Paula Pereira, Ana Luiza Pessoa de Mendonça Angelo, Marcelo Antônio Pascoal Xavier, Alexandre de Magalhães Vieira Machado, Remo Castro Russo","doi":"10.1002/jmr.70002","DOIUrl":"https://doi.org/10.1002/jmr.70002","url":null,"abstract":"<div>\u0000 \u0000 <p>Severe acute respiratory syndrome coronavirus (SARS-CoV), the virus responsible for COVID-19, interacts with the host immune system through complex mechanisms that significantly influence disease outcomes, affecting both innate and adaptive immunity. These interactions are crucial in determining the disease's severity and the host's ability to clear the virus. Given the virus's substantial socioeconomic impact, high morbidity and mortality rates, and public health importance, understanding these mechanisms is essential. This article examines the diverse innate immune responses triggered by SARS-CoV-2's structural proteins, including the spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins, along with nonstructural proteins (NSPs) and open reading frames. These proteins play pivotal roles in immune modulation, facilitating viral replication, evading immune detection, and contributing to severe inflammatory responses such as cytokine storms and acute respiratory distress syndrome (ARDS). The virus employs strategies like suppressing type I interferon production and disrupting key antiviral pathways, including MAVS, OAS-RNase-L, and PKR. This study also explores the immune pathways that govern the activation and suppression of immune responses throughout COVID-19. By analyzing immune sensing receptors and the responses initiated upon recognizing SARS-CoV-2 structural proteins, this review elucidates the complex pathways associated with the innate immune response in COVID-19. Understanding these mechanisms offers valuable insights for therapeutic interventions and informs public health strategies, contributing to a deeper understanding of COVID-19 immunopathogenesis.</p>\u0000 </div>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"38 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143112377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. A. D. B. Amarasiri, Danushka Arachchige, Matthew J. K. Vince, Justin M. Holub
{"title":"Inhibitory Potential and Binding Thermodynamics of Scyllatoxin-Based BH3 Domain Mimetics Targeting Repressor BCL2 Proteins","authors":"H. A. D. B. Amarasiri, Danushka Arachchige, Matthew J. K. Vince, Justin M. Holub","doi":"10.1002/jmr.70001","DOIUrl":"https://doi.org/10.1002/jmr.70001","url":null,"abstract":"<p>The B-cell lymphoma 2 (BCL2) proteins are a class of apoptosis regulators that control the release of apoptogenic factors from mitochondria. Under normal physiological conditions, apoptosis is inhibited through the actions of anti-apoptotic (repressor) BCL2 proteins that bind semi-indiscriminately to the helical BH3 domains of pro-apoptotic (effector) BCL2 proteins. In this work, we developed a series of BH3 domain mimetics by grafting residues from the effector BCL2 protein Bax onto the α-helix of scyllatoxin (ScTx). These so-called “ScTx-Bax” constructs were then used to gain insight into the physicochemical nature of repressor/effector BCL2 interactions. Specifically, we utilized competitive binding and isothermal titration calorimetry (ITC) to investigate the inhibitory potential and binding thermodynamics of ScTx-Bax structural variants that target the repressor protein Bcl-2 (proper) in vitro. Our data show that ScTx-Bax mimetics compete with isolated Bax BH3 domain peptides for Bcl-2 with IC<sub>50</sub> values in the mid-nanomolar range and that greater flexibility within the ScTx-Bax BH3 domain correlates with more effective inhibition. Furthermore, ITC experiments revealed that unstructured ScTx-Bax variants target Bcl-2 with greater entropic, but lower enthalpic, efficiencies than structured ScTx-Bax peptides. These results suggest that entropic contributions to binding Bcl-2 are more favorable for flexible BH3 domains; however, this enhancement is counterbalanced by a moderate enthalpic penalty. Overall, this study improves understanding of how structural properties of effector BH3 domains influence the promiscuous binding patterns of BCL2 proteins and expands the utility of ScTx-based BH3 domain mimetics as molecular tools to study discrete recognition elements that facilitate repressor/effector BCL2 interactions.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"38 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmr.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Serum D-Fucose Binding Lectin With B Cell Mitogenic Activity From the Grub of the Darkling Beetle Zophobas morio","authors":"Ramanathan Nivetha, Mani Meenakumari, Sreeramulu Bhuvaragavan, Ayikkara Peroor Mahi Dev, Sundaram Janarthanan","doi":"10.1002/jmr.70000","DOIUrl":"10.1002/jmr.70000","url":null,"abstract":"<div>\u0000 \u0000 <p>Lectins that can recognize and bind to carbohydrates and glycoconjugates are at the epicentre of research owing to their prospective applications. In the present study, a D-fucose binding lectin from the serum of darkling beetle, <i>Zophobas morio</i> was purified and their mitogenic potential over human B-cells was evaluated. Biochemical assays on the preliminary characterization revealed the occurrence of single D-fucose binding lectin. Through single step affinity chromatography using D-fucose coupled Epoxy-activated Sepharose 6B, lectin (<i>Zm</i>FBL) with a molecular mass of ~192 kDa from the serum of <i>Z</i>. <i>morio</i> was purified with homogeneity. The HA activity of the purified <i>Zm</i>FBL remained stable between the pH 7 and 12 and was thermo-tolerant up to a temperature of 40°C. MALDI-TOF-MS analysis of native lectin disclosed fucose-binding nature of the <i>Zm</i>FBL with mitogenic property. The results of functional analysis of purified <i>Zm</i>FBL on the effect on B-cell proliferation revealed that <i>Zm</i>FBL at the concentrations of 31.25 μg and 62.50 were the ideal concentrations that significantly enhanced (approximately 2.5-fold over control) the proliferation of the B-lymphocyte population up to 72 h of treatment without any cytotoxicity. The outcome of this study could possibly prove beneficial in the investigation on the potential use of <i>Zm</i>FBL as immunostimulant and in immunosuppressive treatments.</p>\u0000 </div>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"38 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Deciphering Saquinavir–Bovine Serum Albumin Interactions: Spectroscopic and Computational Insights","authors":"Vijayakumar Rajendran, Saravanan Kandasamy, Seshan Gunalan, Sekar Kanagaraj, Gugan Kothandan","doi":"10.1002/jmr.3112","DOIUrl":"10.1002/jmr.3112","url":null,"abstract":"<div>\u0000 \u0000 <p>Bovine serum albumin (BSA) plays a crucial role as a carrier protein in plasma, binding various ligands, including drugs. Understanding the interaction between BSA and saquinavir, an antiretroviral drug, is essential for predicting its pharmacokinetics and pharmacodynamics. We employed spectroscopic approaches, including circular dichroism spectrometry and fluorescence spectroscopy, to investigate the binding of saquinavir to BSA. CD studies revealed conformational changes upon saquinavir mesylate binding, and the complex was stable up to 45°C during thermal denaturation. Saquinavir quenched the intrinsic fluorescence of BSA, indicating static quenching due to complex formation. Additionally, molecular docking simulations were performed to elucidate the favored binding site and interactions. The molecular docking results revealed that Subdomains IIA and IIB, which are proximal to Sudlow Site I, are the principal binding sites for the antiviral drug saquinavir. The ligand-bound pose of BSA also revealed that residue Trp213, which is adjacent to saquinavir, further validated the results of the fluorescence quenching assay, suggesting that residue Trp213 is quenched upon binding with saquinavir. MD simulations allowed us to explore the dynamic behavior of the BSA–saquinavir complex over time. We observed conformational fluctuations, solvent exposure, flexibility of binding pockets, free energy landscape, and binding energy. This study enhances our understanding of drug–protein interactions and contributes to drug development and optimization.</p>\u0000 </div>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"38 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}