Journal of Biomolecular Structure & Dynamics最新文献

{"title":"MCNN-AAPT: accurate classification and functional prediction of amino acid and peptide transporters in secondary active transporters using protein language models and multi-window deep learning.","authors":"Muhammad Shahid Malik, Van The Le, Syed Muazzam Ali Shah, Yu-Yen Ou","doi":"10.1080/07391102.2024.2431664","DOIUrl":"https://doi.org/10.1080/07391102.2024.2431664","url":null,"abstract":"<p><p>Secondary active transporters play a crucial role in cellular physiology by facilitating the movement of molecules across cell membranes. Identifying the functional classes of these transporters, particularly amino acid and peptide transporters, is essential for understanding their involvement in various physiological processes and disease pathways, including cancer. This study aims to develop a robust computational framework that integrates pre-trained protein language models and deep learning techniques to classify amino acid and peptide transporters within the secondary active transporter (SAT) family and predict their functional association with solute carrier (SLC) proteins. The study leverages a comprehensive dataset of 448 secondary active transporters, including 36 solute carrier proteins, obtained from UniProt and the Transporter Classification Database (TCDB). Three state-of-the-art protein language models, ProtTrans, ESM-1b, and ESM-2, are evaluated within a deep learning neural network architecture that employs a multi-window scanning technique to capture local and global sequence patterns. The ProtTrans-based feature set demonstrates exceptional performance, achieving a classification accuracy of 98.21% with 87.32% sensitivity and 99.76% specificity for distinguishing amino acid and peptide transporters from other SATs. Furthermore, the model maintains strong predictive ability for SLC proteins, with an overall accuracy of 88.89% and a Matthews Correlation Coefficient (MCC) of 0.7750. This study showcases the power of integrating pre-trained protein language models and deep learning techniques for the functional classification of secondary active transporters and the prediction of associated solute carrier proteins. The findings have significant implications for drug development, disease research, and the broader understanding of cellular transport mechanisms.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-10"},"PeriodicalIF":2.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687222","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":"Physicochemical, medicinal chemistry, and ADMET characteristics of bee antimicrobial peptides as natural bio-preservatives to extend food shelf life: a roadmap for food safety regulation.","authors":"Roy Dinata, Chettri Arati, Ahmed-Laskar Saeed, Bose Manikandan, Giri Abinash, Buragohain Pori, Rema Momin Bidanchi, Vikas Kumar Roy, Guruswami Gurusubramanian","doi":"10.1080/07391102.2024.2429181","DOIUrl":"https://doi.org/10.1080/07391102.2024.2429181","url":null,"abstract":"<p><p>Antimicrobial peptides (AMPs) are gaining popularity as potential substitutes for conventional antibiotics and bio-preservatives in response to an increase in antimicrobial resistance cases. However, their poor pharmacokinetic profiles limit their applicability. This study using ADMETlab, OECD QSAR toolbox, and VEGA HUB virtual environments profiled 82 peptide sequences of seven bee antimicrobial peptides (BAMPs: abaecin, apamin, apisimin, apidaecin, defensin, hymenoptaecin, and melittin) using 81 descriptors combining physicochemical, medicinal chemistry, ADMET, and toxicophore criteria. BAMPs adhere to key drug-like physicochemical features and drug-ability regulations set forth by pharmaceutical giants, including Lipinski, Pfizer, and GlaxoSmithKline. BAMPs have been predicted to demonstrate favorable cell permeability, high water solubility, oral bioavailability, no blood-brain barrier penetration, oral and intestinal absorption, excretion, and a high therapeutic index. They function as non-substrates of p-glycoprotein and do not alter the pharmacokinetic effects of P-gp substrates. None of BAMPs were found to inhibit cytochrome P450 enzymes, indicating their potential to promote drug clearance and metabolism. BAMPs are safe from adverse reactions, free of respiratory toxicity, hERG blockers, hepatotoxicity, sensitizers, carcinogens, and mutagens. They are non-corrosive, non-irritating to the eyes, non-bioaccumulative, non-ecotoxic, antibacterial, antifungal, and antiviral, low toxic with no toxicophore or PAINS alerts recorded. They are non-toxic to various receptors, including gonadal and stress receptors, PPAR-γ, mitochondrial membrane receptor, heat shock element, and p53. Seven BAMPs have been tested for their drug-like properties, supporting their potential as potential leads for the pharmaceutical and food industries as antimicrobial agents and bio-preservatives. Future studies should optimize bee peptide expression in biological systems.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-29"},"PeriodicalIF":2.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687224","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":"<i>In silico</i> strategies to recognize pharmacological constraints contrary to COX-2 and 5-LOX.","authors":"Kumari Neha, Gagandeep Singh, Mrityunjay Singh, Shailendra Asthana, Sharad Wakode","doi":"10.1080/07391102.2024.2425404","DOIUrl":"https://doi.org/10.1080/07391102.2024.2425404","url":null,"abstract":"<p><p>COX-2 and 5-LOX are major enzymes implicated in inflammatory processes and have a crucial role in the pathogenesis of inflammatory disorders and malignancies. Designing antagonists that may concurrently interact with several receptors is a viable technique; thus, blocking these two targets with a single chemical compound might provide an efficient therapeutic approach. In-silico approaches have been employed to find polypharmacological inhibitors, especially for drug repurposing and multitarget drug design. Here, virtual screening of designed oxygen-containing heterocyclic series from prior literature was used to locate a feasible dual inhibitor against COX-2 and 5-LOX. Among these, 5-phenyl-2-(pyridin-3-yl)oxazol-4-yl cyclohexyl(methyl)sulfamate (N<b>14</b>) and 5-phenyl-2-(pyridin-4-yl)oxazol-4-yl benzenesulfonate (N<b>16</b>) was found to more promising with good interaction energy against COX-2 (-9.5 and -9.4 kcal/mol) and 5-LOX (-8.6 and -7.6 kcal/mol). Additionally, it also fulfilled the ADME/T parameters revealed to be drug-like, as anticipated by Lipinski's rule of five and Veber's rule. Furthermore, the molecular dynamics, free binding energy and post-processing analysis indicate N<b>14</b> and N<b>16</b> appears as a promising candidates with a novel molecular scaffold that could be examined further as a polypharmacological anticancer therapeutic candidate to explore further for the development.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687221","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":"Theoretical investigations of some isolated compounds from <i>Calophyllum flavoramulum</i> as potential antioxidant agents and inhibitors of AGEs.","authors":"Houria Bentoumi, Abdeslem Bouzina, Aïcha Amira, Omar Sekiou, Djawhara Chohra, Loubna Ferchichi, Rachida Zerrouki, Nour-Eddine Aouf","doi":"10.1080/07391102.2024.2428375","DOIUrl":"https://doi.org/10.1080/07391102.2024.2428375","url":null,"abstract":"<p><p>In this paper, we have attempted a theoretical calculation of some plant-isolated compounds as potential inhibitors of oxidative stress and Advanced Glycation Endproducts (AGEs). Herein, theoretical reactivity indices based on the CDFT theory were computed to explore the reactivity of five isolated products from <i>Calophyllum flavoramulum.</i> Global reactivity indices based on HOMO and LUMO energy such as electronic chemical potential, hardness, electrophilicity and the local reactivity descriptors Parr function, molecular electrostatic potentials(MEP), electrostatic potential (ESP) and thermodynamic parameters for the studied compounds are computed and discussed using DFT method and two functionals B3LYP and CAM-B3LYP with 6-31 G(d,p) basis set. The free radical scavenging activity mechanisms (HAT, SET-PT, and SPLET) of some of the isolated products with DPPH are also presented in this work. SET-PT mechanism of the antiradical activity is found to be thermodynamically favorable. Furthermore, a molecular docking study with RAGE receptor and AtGSTF2 enzyme was conducted, in which flavonoids <b>4</b> and <b>5</b> show a low binding affinity with -8.42 and -10.49 kcal/mol for RAGE, -8.67 and -9.00 kcal/mol for AtGSTF2. After the encouraging outcomes from the molecular docking study, the 4-AtGSTF2 and 5-RAGE complex were subjected to 200 ns molecular dynamics simulation using Desmond, where both studied systems exhibited remarkable stability throughout the 200 ns simulations. Also, the MM-GBSA method was measured by calculating the binding free energy using the individual energy components. Finally, the ADMET predictions were assessed to anticipate the behavior of a drug candidate within the human body.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-27"},"PeriodicalIF":2.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681822","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":"How to measure the probability of uracil chain tautomers as nucleotide bases in RNA?","authors":"Parisa Fereidounpour, Shapour Ramazani","doi":"10.1080/07391102.2024.2428827","DOIUrl":"https://doi.org/10.1080/07391102.2024.2428827","url":null,"abstract":"<p><p>The current research focuses on exploring tautomerism in uracil. 47 tautomers were found that varied in significance in RNA and stability. To discover these molecules, diverse potential energy levels were explored, and corresponding transition states were found in these pathways. But the imperative thing that was taken note in this investigation is that for the first time, a method was detailed for the probability of forming distinctive molecules relative to each other. In this method, the conversion of uracil and its tautomers, which together turn into 47 molecules, was composed as a Markov chain. Then, the transition matrix was explained using its support, whose components are the probability of creating molecules from each step. At last, by multiplying this matrix by <b><i>n</i></b> times, the probability of forming different molecules was obtained. Moreover, by solving this matrix at different times, it is conceivable to appear which molecules can be converted to uracil sooner. It was appeared that a few tautomers act as transitory absorption point or temporary terminal states and other molecules, to begin with convert to these molecules before turning into uracil.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675939","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":"Paclitaxel and myricetin encapsulated hemoglobin nanoparticles: characterization and application.","authors":"Ishaleena Chowdhury, Goutam Pramanik, Aparna Dutta, Debashis Majumder, Chabita Saha","doi":"10.1080/07391102.2024.2429197","DOIUrl":"https://doi.org/10.1080/07391102.2024.2429197","url":null,"abstract":"<p><p>Hb is used as a carrier protein to encapsulate hydrophobic drugs PTX and MYN and has applications in cancer treatment. PTX and MYN encapsulated Hb NPs are synthesized by the acid denature method and are characterized by spectroscopic and electron microscopic techniques. The binding constant calculated for Hb and PTX is 3.83 x 10⁸ M^-1, which is the highest in the pH range tested for both drugs. The CD spectra also demonstrated maximum denaturation of Hb at pH 5.0 evidencing the opening of the Hb hydrophobic core. The acidic condition at pH 5.0 is optimized for the synthesis of drug- encapsulated NPs. FTIR spectra of Hb PTX NPs recorded higher shifts in the OH/carboxyl peak compared to Hb-MYN. SEM images of Hb-PTX NPs highlight the tetrahedral structure of the NPs and the round shape of Hb-MYN NPs. The size of Hb-MYN and Hb-PTX is around 38.0 and 44.0 nm respectively as measured by DLS. PTX-Hb NPs demonstrated higher dose-dependent apoptosis-inducing efficacy than MYN-Hb in the K562 cells.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675942","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":"Prediction of SHP2-E76K binding sites based on molecular dynamics simulation and Markov algorithm.","authors":"Si-Pei Zhang, Li-Juan Chen, Zhen-Liang Shi, Xin Li, Ying Ma","doi":"10.1080/07391102.2024.2431193","DOIUrl":"10.1080/07391102.2024.2431193","url":null,"abstract":"<p><p>SHP2-E76K, a mutant encoded by the PTPN11 gene, was associated with various solid tumors, such as lung cancer, glioblastoma, and intellectual disability. SHP2-E76K has become potential drug targets, while there was no effective inhibitor against the mutant currently. At present, the crystal complex structure of SHP099 with SHP2-E76K has been reported in the RCSB PDB protein data bank, however, the dynamic structure of SHP099 binding to the active center of SHP2-E76K protein was still lacking. Therefore, this study used molecular dynamics simulation and Markov model to characterize the kinetics of the inhibitor SHP099 with SHP2-E76K enzyme and to determine the active binding site, which would give a hint of a vital enzyme-substrate interaction in atomistic detail that proposed the potential to be applied for the discovery of more effective SHP2-E76K inhibitors and, in broader terms, dynamic protein-drug interactions.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668152","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":"Multistep structure-based virtual screening approach toward the identification of potential potent SARS-CoV-2 Mpro inhibitors.","authors":"Taghreed A Majrashi, Mahmoud A El Hassab, Mohammed K Abdel-Hamid Amin, Eslam B Elkaeed, Moataz A Shaldam, Ahmed A Al-Karmalawy, Wagdy M Eldehna","doi":"10.1080/07391102.2024.2427375","DOIUrl":"https://doi.org/10.1080/07391102.2024.2427375","url":null,"abstract":"<p><p>Around four years have passed since the globe was shaken by the COVID-19 pandemic, triggered by SARS-CoV-2, affecting almost one billion individuals worldwide and claiming the lives of millions. Despite stringent safety measures and the swift expansion of vaccination initiatives, managing waves of illness has proven challenging. Given its crucial involvement in replication and notable conservation, our team persisted in focusing on the SARS-CoV-2 main protease enzyme (Mpro) as a highly promising therapeutic objective. Accordingly, a multistep computer-aided drug discovery process was used in this study to elucidate potential lead candidates targeting SARS-CoV-2 Mpro. A protein-ligand interaction fingerprint (PLIF) tool was utilized to help design a structure-based pharmacophore based on critical interactions between known ligands and the Mpro active site. The produced pharmacophore was used to filter a fraction of the ZINC database of chemical substances, resulting in 703 possible hits. All the filtered compounds achieved acceptable docking scores and four compounds achieved higher docking scores of selected Mpro inhibitor reference, and the top-ranked compound W1 (ZINC000150656136) was selected for more simulations. A combination of traditional molecular dynamics (MD) and MM-PBSA was used in the final step. W1 has been predicted to engage with multiple essential interactions with key residues in the Mpro active with a docking score and binding free energy of 11.1 kcal/mol and -324.7 ± 9.7 Kj/mol, respectively. As a result, we propose <b>W1</b> as a lead compound candidate towards the SARS-CoV-2 Mpro enzyme that can be forwarded for experimental validation and clinical studies for COVID-19 management.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-10"},"PeriodicalIF":2.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675940","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":"Novel tetrazolyl-1,2,3-triazole derivatives as potent antimicrobial targets: design, synthesis and molecular docking techniques.","authors":"Kumaraswamy Sadineni, Sharath Babu Haridasyam, Venkanna Gujja, Venkatanaryana Muvvala, Sunil Kumar Nechipadappu, Kishore Veera Venkata Nanda Pilli, Kalyani Chepuri, Tejeswara Rao Allaka","doi":"10.1080/07391102.2024.2425830","DOIUrl":"https://doi.org/10.1080/07391102.2024.2425830","url":null,"abstract":"<p><p>The main objective of this study is to produce novel triazoles-loaded tetrazoles, which are crucial in the development of prospective therapeutic agents in medicinal chemistry. Recent investigations have found a wide range of uses for these derivatives, and they are prospective lead molecules for the synthesis of substances with enormous therapeutic utility for various diseases, especially for bacterial therapy. New series of 1,2,3-triazole derivatives have been synthesized from methyl (2S,4S)-4-azido-1-(2,4-difluoro-3-methylbenzoyl)pyrrolidine-2-carboxylate (<b>5</b>) using a well-established click reaction that has several advantages to afford a novel heterocyclic compound based on tetrazole moieties. The structures of the new compounds were ascertained by spectral means (IR, NMR: ¹H and ¹³C) and mass spectrum. All the synthesized compounds were assessed <i>in vitro</i> antimicrobial activity against Gram-+ve (<i>S. pyogenes</i>, <i>S. aureus</i> and <i>B. subtilis</i>), Gram-negative (<i>E. coli</i> and <i>P. aeruginosa</i>) bacterial and fungal strains <i>A. flavus</i> and <i>C. albicans</i>. The prepared compounds <b>7b</b> and<b>7f</b> proved to have strong impact on <i>S. aureus</i> and <i>S. pyogenes</i> strains with MICs of 2.5 µg/mL and 1.5 µg/mL respectively. Among the tested compounds, hybrids <b>7b</b>, <b>7f</b>, <b>7h</b>, and <b>7i</b> exhibited exceptional antifungal susceptibilities against <i>C. albicans</i> with zone of inhibition 25 ± 0.2, 30 ± 0.3, 30 ± 0.1, and 28 ± 0.2 mm respectively, which is stronger than fluconazole (28 ± 0.1 mm). The capacity of ligand <b>7f</b> to form a stable compound on the active site of <i>S. aureus</i> complex with DNA Gyrase (2XCT) was confirmed by docking studies using amino acids Ala233(A), Arg234(A), Gly283(A), Ser286(A), Lys52(A), His280(A), Gly51(A), His282(A) and Val246(A). Furthermore, the physicochemical and ADME (absorption, distribution, metabolism, and excretion) filtration molecular properties, estimation of toxicity, and bioactivity scores of these scaffolds were evaluated.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675941","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":"Natriuretic effect of 4',5-dihydroxy-6,7-methylenedioxyflavonol-3-<i>O</i>-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranoside from <i>Boldoa purpurascens: in silico</i> and <i>in vivo</i> studies.","authors":"Yudith Cañizares-Carmenate, Dulce M González-Mosquera, Yunier Perera-Sardiña, Erix W Hernández-Rodríguez, Roberto Díaz-Amador, Juan A Castillo-Garit, Emmy Tuenter","doi":"10.1080/07391102.2024.2426075","DOIUrl":"https://doi.org/10.1080/07391102.2024.2426075","url":null,"abstract":"<p><p>Aqueous leaf extracts of <i>Boldoa purpurascens</i> are widely used because of their diuretic, natriuretic, antiurolithiatic, anti-inflammatory and antihypertensive properties. The major component of the extract is the flavonoid 4',5-dihydroxy-6,7-methylenedioxyflavonol-3-<i>O</i>-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranoside, but it is not known if this compound is responsible for the biological activity. The objective of this work is to develop effective <i>in silico</i> tools that allow predicting the possible activity of the flavonoid aglycone as an inhibitor of metalloproteases that regulate renal fluid excretion. First, a mathematical ligand-based classification model was developed, using an artificial intelligence and machine learning technique of support vector machines to find the relationship between chemical structure and biological activity. This showed good fit of the statistical parameters with an accuracy greater than 90%, offering <i>a priori</i> information of the flavonoid activity. Subsequently, the flavonoid aglycone was docked to the active site of the enzymes thermolysin (PDB: 6YMS), angiotensin-converting enzyme (PDB: 6TT4) and neprilysin (PDB: 6SUK) using the Extra Precision glide method (Glide-XP), showing conformations with binding energies lower than -5 Kcal/mol. In this study, possible interactions were determined at the catalytic site, where the coordination of negatively charged pharmacophoric groups with the zinc atom of these enzymes is observed. Finally, a preliminary <i>in vivo</i> evaluation was carried out using a diuresis-natriuresis model with sodium quantification in urine which revealed good activity profiles. These results are in correspondence with the ethnopharmacological use of the plant as a diuretic-natriuretic and for the treatment of hypertension.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-11"},"PeriodicalIF":2.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648341","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}