Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Behenic Acid as a multi-target inhibiting antibacterial phytochemical against <i>Vibrio parahaemolyticus</i> and <i>Aeromonas hydrophila</i> for effective management of aquaculture infections: an in-silico, in-vitro & in-vivo experimentation.","authors":"Lokesh Ravi, Ajith Kumar K, Shree Kumari G R, Jesna Mathew, Harshitha S, Mukti Panda, Shivani S, Ayona Paul, Chandana Ts, Aswani Anil, Megha J K, Taanusiya Mukherjee, Sneha Bhattacharjee, Manu Raveendran Nair, Subhanjan V, Mohanasrinivasan V, Pratishtha Jain","doi":"10.1080/07391102.2024.2317988","DOIUrl":"10.1080/07391102.2024.2317988","url":null,"abstract":"<p><p>Multi-Target Inhibitors are the upcoming frontrunners of the antibiotic world as they provide significant advantage over drug resistance development. Antibacterial drug discovery research, requires more robust and innovative approaches such as multi-target inhibiting drugs, which over comes the innate hurdles in the field of antibiotics. In this current study, a curated set of 5,112 phytochemical molecules were virtually screened for its multi-target inhibition potential against 7 antibacterial protein drug-targets. Behenic Acid was identified to be the most significant phytochemical molecule with potential to inhibit Catalase Peroxidase (KatG), Adenylosuccinate Synthetase (ADSS) and Pyridoxine 5'-Phosphate Synthase (PdxJ), based on SeeSAR and AutoDock Vina results. Further, the inhibition potential of Behenic Acid was validated using 500 ns Molecular Dynamics (MD) Simulation based on Desmond analysis. Behenic Acid was further investigated in-vitro using agar-well-diffusion and Minimal Inhibitory Concentration (MIC) assay, where it demonstrated 20 ± 1mm zone-of-inhibition and 50 µg/ml MIC value against both <i>Vibrio parahaemolyticus</i> and <i>Aeromonas hydrophila</i>. Zebrafish based investigations was carried to confirm the in-vivo antibacterial efficacy of Behenic Acid. It was observed that, there is a progressive dose-dependent recovery from the bacterial infection, with highest recovery and survival observed in fishes fed with 100 µg/day of Behenic Acid. Results of the in-vitro and in-vivo assays strongly support the in-silico prediction of the antibacterial activity of Behenic Acid. Based on the results presented in this study, it is concluded that, Behenic Acid is a strong multi-target antibacterial phytochemical, that exerts antagonism against aquaculture bacterial pathogens such as <i>V. parahaemolytics</i> and <i>A. hydrophila.</i></p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6078-6093"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729747","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":"Computational screening of phytocompounds from <i>C. amboinicus</i> identifies potential inhibitors of influenza A (H3N2) virus by targeting hemagglutinin.","authors":"Kadabagere Narayanaswamy Hemavathi, Sushil Kumar Middha, Rajesh Raju, Rajendra Pilankatta, Thottethodi Subrahmanya Keshava Prasad, Chandran S Abhinand","doi":"10.1080/07391102.2024.2424940","DOIUrl":"10.1080/07391102.2024.2424940","url":null,"abstract":"<p><p>The H3N2 subtype of the influenza A virus continues to be a notable public health issue due to its association with seasonal epidemics and severe human morbidity. The constrained effectiveness of current antiviral medications, combined with the inevitable emergence of drug-resistant variants, mandates the exploration of innovative therapeutic approaches. This study focuses on the identification of phytocompounds from <i>Coleus amboinicus</i> with the potential to target hemagglutinin, viral protein involved in viral entry by binding to sialyl glycoconjugates receptors on the surface of host cells. Molecular docking studies were carried out to assess the efficacy of <i>C. amboinicus</i> phytocompounds with hemagglutinin receptor-binding site. The study revealed that among the 84 signature phytocompounds, isosalvianolic acid and salvianolic acid C showed the highest docking scores and favourable intermolecular interactions. Pharmacokinetic analysis and Pan-assay interference compounds (PAINS) filtering confirmed that isosalvianolic acid meets the criteria outlined in Lipinski's rule of five, exhibits favourable ADMET profiles and passes PAINS filters. Furthermore, the molecular dynamics simulations followed by radius of gyration (Rg), solvent accessible surface area (SASA), and MM-PBSA calculations for binding free energy, verified the stability of the docked complexes. Together, the study identifies isosalvianolic acid as a promising inhibitor of the H3N2 virus by binding to hemagglutinin, indicating its potential as a strategy for therapeutic intervention.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6303-6315"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621270","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":"Probing the interaction behavior of Nano-Resveratrol with α-lactalbumin in the presence of β-lactoglobulin and β-casein: spectroscopy and molecular simulation studies.","authors":"Zahra Ghadamgahi, Alireza Motavalizadehkakhky, Jamshid Mehrzad, Zeinab Amiri-Tehranizadeh, Jamshidkhan Chamani","doi":"10.1080/07391102.2024.2316774","DOIUrl":"10.1080/07391102.2024.2316774","url":null,"abstract":"<p><p>The main purpose of this research was to evaluate the role of α-lactalbumin (α-LA), β-lactoglobulin (β-LG), and β-Caseins (β-CN) in the binding interaction between Nano Resveratrol (Nano Res), as binary and ternary systems. This investigation was fulfilled through the application of multi-spectroscopic, transmission electron microscopy (TEM), field emission scanning electron microscope (FE-SEM), conductometry, isothermal titration calorimetry (ITC), and molecular dynamics (MD) simulation techniques. Fluorescence spectroscopy observations illustrated the effectiveness of Nano Res throughout the quenching of α-LA, (α-LA-β-LG), and (α-LA-β-CN) complexes, confirming the occurrence of interaction through the combination of static and dynamic mechanisms. An enhancement in the temperature of all three complexes caused a decrease in their K_sv and K_b values, which indicates the static and dynamic behavior of their interactions. The obtained thermodynamic parameters proved the dominance of electrostatic interaction as the binding force of both binary and ternary systems. The observed properties of Tyr or Trp residues in proteins through the data of synchronous spectroscopy at Δλ = 15 and 60 nm, respectively, demonstrated the closer positioning of (α-LA-β-CN) complex to the proximity of Trp residues when compared to the two other cases. According to the resonance light scattering (RLS) measurements, the detection of a much greater RLS intensity in (α-LA-β-CN) Nano Res complex suggested the production of a larger complex. Furthermore, the conductometry outcomes displayed an increase in molar conductivity and therefore approved the occurrence of interaction between Nano Res and proteins in both binary and ternary systems. The spherical shape of Nano Res was confirmed through the results of FE-SEM and TEM analyses. The conformational changes of proteins throughout the binding of Nano Res was evaluated by circular dichroism (CD) technique, while molecular docking and MD simulations affirmed the binding of Nano Res to α-LA, (α-LA-β-LG), and (α-LA-β-CN) complexes as binary and ternary systems. These <i>In Silico</i> study data confirm the results of <i>in vitro</i> assessments. The occurrence of changes in the secondary structure of β-galactosidase was implied through the increased enzyme catalytic activity induced by the interaction of different lactose concentrations.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6832-6852"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722733","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":"In-silico analysis of potential anticancer drug for NEK7 and PPP1CA proteins overexpressed in pancreatic ductal adenocarcinoma.","authors":"Safa Adrees, Anam Imtiaz, Aiman Yaseen, Muhammad Irfan Fareed, Waqar Anwar, Asma Ashraf, Rana Muhammad Kamran Shabbir, Shaista Andlib, Mureed Hussain, Asma Tariq, Rana Muhammad Mateen, Muhammad Arif Nadeem Saqib, Rukhsana Parveen","doi":"10.1080/07391102.2024.2318484","DOIUrl":"10.1080/07391102.2024.2318484","url":null,"abstract":"<p><p>NIMA-related kinase 7 (NEK7) and phosphoprotein phosphatase-1 catalytic subunit alpha (PPP1CA) are the most common proteins overexpressed in pancreatic ductal adenocarcinoma, which is the most common type of pancreatic cancer. The goal of the current study was to identify a possible NEK7 and PPP1CA therapeutic inhibitor. For this investigation, 5000 compounds were retrieved from the IMPPAT library of phytochemicals, which were docked with our respective target proteins. Also, a reference compound, gemcitabine, which is a Food and Drug Administration (FDA) approved drug, was docked with the target proteins. The binding energy of the reference compound for both the targeted proteins was -6.5 kcal/mol. The common ligand with the lowest binding energy for both targets is boeravinone B (PubChem ID: 14018348) with -9.2 kcal/mol of NEK7 and -7.6 kcal/mol for PPP1CA. The compound was further investigated through density function theory (DFT) and molecular dynamic simulation analysis. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and hydrogen bonding analysis indicated the stability of the boeravinone B with the target proteins (NEK7 and PPP1CA).</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6581-6597"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101655","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":"Exploring the role of TLK2 mutation in tropical calcific pancreatitis: an <i>in silico</i> and molecular dynamics simulation study.","authors":"Ashish Shrivastava, Sri Krishna Jayadev Magani, Kiran Bharat Lokhande, Madhusudan Chintakhindi, Ashutosh Singh","doi":"10.1080/07391102.2024.2329797","DOIUrl":"10.1080/07391102.2024.2329797","url":null,"abstract":"<p><p>Tropical calcific pancreatitis (TCP) is a juvenile form of non-alcoholic chronic pancreatitis seen exclusively in tropical countries. The disease poses a high risk of complications, including pancreatic diabetes and cancer, leading to significant mortality due to poor diagnosis and ineffective treatments. This study employed whole exome sequencing (WES) of 5 TCP patient samples to identify genetic variants associated with TCP. Advanced computational techniques were used to gain atomic-level insights into disease progression, including microsecond-scale long MD simulations and essential dynamics. <i>In silico</i> virtual screening was performed to identify potential therapeutic compounds targeting the mutant protein using the Asinex and DrugBank compound library. WES analysis predicted several single nucleotide variants (SNVs) associated with TCP, including a novel missense variant (c.T1802A or p.V601E) in the TLK2 gene. Computational analysis revealed that the p.V601E mutation significantly affected the structure of the TLK2 kinase domain and its conformational dynamics, altering the interaction profile between ATP and the binding pocket. These changes could impact TLK2's kinase activity and functions, potentially correlating with TCP progression. Promising lead compounds that selectively bind to the TLK2 mutant protein were identified, offering potential for therapeutic interventions in TCP. These findings hold great potential for future research.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6996-7015"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158258","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":"MOCS, a novel classifier system integrated multimoics analysis refining molecular subtypes and prognosis for skin melanoma.","authors":"Juelan Ye, Fuchun Liu, Luoshen Zhang, Chunbiao Wu, Aimin Jiang, Tianying Xie, Hao Jiang, Zhenxi Li, Peng Luo, Jian Jiao, Jianru Xiao","doi":"10.1080/07391102.2024.2329305","DOIUrl":"10.1080/07391102.2024.2329305","url":null,"abstract":"<p><strong>Purpose: </strong>The present investigation focuses on Skin Cutaneous Melanoma (SKCM), a melanocytic carcinoma characterized by marked aggression, significant heterogeneity, and a complex etiological background, factors which collectively contribute to the challenge in prognostic determinations. We defined a novel classifier system specifically tailored for SKCM based on multiomics.</p><p><strong>Methods: </strong>We collected 423 SKCM samples with multi omics datasets to perform a consensus cluster analysis using 10 machine learning algorithms and verified in 2 independent cohorts. Clinical features, biological characteristics, immune infiltration pattern, therapeutic response and mutation landscape were compared between subtypes.</p><p><strong>Results: </strong>Based on consensus clustering algorithms, we identified two Multi-Omics-Based-Cancer-Subtypes (MOCS) in SKCM in TCGA project and validated in GSE19234 and GSE65904 cohorts. MOCS2 emerged as a subtype with poor prognosis, characterized by a complex immune microenvironment, dysfunctional anti-tumor immune state, high cancer stemness index, and genomic instability. MOCS2 exhibited resistance to chemotherapy agents like erlotinib and sunitinib while sensitive to rapamycin, NSC87877, MG132, and FH355. Additionally, ELSPBP1 was identified as the target involving in glycolysis and M2 macrophage infiltration in SKCM.</p><p><strong>Conclusions: </strong>MOCS classification could stably predict prognosis of SKCM; patients with a high cancer stemness index combined with genomic instability may be predisposed to an immune exhaustion state.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6650-6666"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331737","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":"Molecular dynamics simulations provide insights into ULK-101 potency and selectivity toward autophagic kinases ULK1/2.","authors":"Robert M Vaughan, Bradley M Dickson, Katie R Martin, Jeffrey P MacKeigan","doi":"10.1080/07391102.2024.2425833","DOIUrl":"10.1080/07391102.2024.2425833","url":null,"abstract":"<p><p>Kinase domains are highly conserved within proteins in both sequence and structure. Many factors, including phosphorylation, amino acid substitutions or mutations, and small molecule inhibitor binding, influence conformations of the kinase domain and enzymatic activity. ULK1 and ULK2 are serine/threonine kinases that serve important roles in autophagy, an intracellular recycling process capable of degrading proteins and organelles <i>via</i> fusion with lysosomes. ULK1/2 are emerging as therapeutic targets in human cancer, particularly KRAS-driven malignancies. Here, we performed molecular dynamics (MD) simulations to hypothesize bound poses for the ULK1/2 small molecule inhibitor, ULK-101. We observed stable bound states for ULK-101 to the adenosine triphosphate (ATP)-binding site of ULK2, coordinated by hydrogen bonding with the hinge backbone and the catalytic lysine sidechain. Notably, ULK-101 occupies a hydrophobic pocket associated with the N-terminus of the αC-helix. Large movements in the phosphate-binding loop (P-loop) are also associated with ULK-101 inhibitor binding and exit from ULK2. Together, our data support a model to explain ULK-101 potency toward ULK1/2.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"7106-7113"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of thiazolidinedione-based pancreatic lipase inhibitors as anti-obesity agents: synthesis, <i>in silico</i> studies and pharmacological investigations.","authors":"Prashant Dhiman, Nisha Yadav, Prashant S Auti, Shalini Jaswal, Gurpreet Singh, Sidharth Mehan, Balaram Ghosh, Atish T Paul, Vikramdeep Monga","doi":"10.1080/07391102.2024.2310799","DOIUrl":"10.1080/07391102.2024.2310799","url":null,"abstract":"<p><p>A series of new 2,5-disubstituted arylidene derivatives of thiazolidinedione (<b>16a-e, 17a-d, 18a-c</b>) designed using molecular hybridization approach were synthesized, structurally characterized, and explored for their anti-obesity potential <i>via</i> inhibition of Pancreatic Lipase (PL). Compound <b>18a</b> presented the most potent PL inhibitory activity with IC₅₀ = 2.71 ± 0.31 µM, as compared to the standard drug, Orlistat (IC₅₀ = 0.99 µM). Kinetic study revealed reversible competitive mode of enzyme inhibition by compound <b>18a</b> with an inhibitory constant value of 1.19 µM. The most promising compound <b>18a</b> revealed satisfactory binding mode within the active site of the target protein (human PL, PDB ID: 1LPB). Also, MM/PBSA binding free energy and molecular dynamics (MD) simulation analysis were performed for the most promising compound <b>18a</b>, which showed potent inhibition according to the results of <i>in vitro</i> studies. Furthermore, a stable conformation of the 1LPB-ligand suggested the stability of this compound in the dynamic environment. The ADME and toxicity analysis of the compounds were examined using web-based online platforms. Results of <i>in vivo</i> studies confirmed the anti-obesity efficacy of compound <b>18a</b>, wherein oral treatment with compound <b>18a</b> (30 mg/kg) resulted in a significant reduction in the body weight, BMI, Lee index, feed intake (in Kcal), body fat depots and serum triglycerides. Compound <b>18a</b> significantly decreased the levels of serum total cholesterol (TC) to 128.6 ± 0.59 mg/dl and serum total triglycerides (TG) to 95.73 ± 0.67 mg/dl as compared to the HFD control group. The present study identified disubstituted TZD derivatives as a new promising class of anti-obesity agents.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5756-5778"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691884","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 and characterization of domain-specific inhibitors of DENV NS3 and NS5 proteins by in silico screening methods.","authors":"Johnson Samuel, Sanjay Ghosh, Saravanamuthu Thiyagarajan","doi":"10.1080/07391102.2024.2313161","DOIUrl":"10.1080/07391102.2024.2313161","url":null,"abstract":"<p><p>The dengue virus (DENV) infects approximately 400 million people annually worldwide causing significant morbidity and mortality. Despite advances in understanding the virus life cycle and infectivity, no specific treatment for this disease exists due to the lack of therapeutic drugs. In addition, vaccines available currently are ineffective with severe side effects. Therefore, there is an urgent need for developing therapeutics suitable for effective management of DENV infection. In this study, we adopted a drug repurposing strategy to identify new therapeutic use of existing FDA approved drug molecules to target DENV2 non-structural proteins NS3 and NS5 using computational approaches. We used Drugbank database molecules for virtual screening and multiple docking analysis against a total of four domains, the NS3 protease and helicase domains and NS5 MTase and RdRp domains. Subsequently, MD simulations and MM-PBSA analysis were performed to validate the intrinsic atomic interactions and the binding affinities. Furthermore, the internal dynamics in all four protein domains, in presence of drug molecule binding were assessed using essential dynamics and free energy landscape analyses, which were further coupled with conformational dynamics-based clustering studies and cross-correlation analysis to map the regions that exhibit these structural variations. Our comprehensive analysis identified tolcapone, cefprozil, delavirdine and indinavir as potential inhibitors of NS5 MTase, NS5 RdRp, NS3 protease and NS3 helicase functions, respectively. These high-confidence candidate molecules will be useful for developing effective anti-DENV therapy to combat dengue infection.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5819-5833"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706893","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":"A hierarchical approach towards identification of novel inhibitors against L, D-transpeptidase YcbB as an anti-bacterial therapeutic target.","authors":"Abdullah S Alawam, Lina M Alneghery, Maher S Alwethaynani, Mubarak A Alamri","doi":"10.1080/07391102.2024.2322619","DOIUrl":"10.1080/07391102.2024.2322619","url":null,"abstract":"<p><p>The bacterial cell wall, being a vital component for cell viability, is regarded as a promising drug target. The L, D-Transpeptidase YcbB enzyme has been implicated for a significant role in cell wall polymers cross linking during typhoid toxin release, β-lactam resistance and outer membrane defect rescue. These observations have been recorded in different bacterial pathogens such as <i>Salmonella Typhimurium</i>, <i>Citrobacter rodentium</i>, and <i>Salmonella typhi</i>. In this work, we have shown structure based virtual screening of diverse natural and synthetic drug libraries against the enzyme and revealed three compounds as LAS_32135590, LAS_34036730 and LAS-51380924. These compounds showed highly stable energies and the findings are very competitive with the control molecule ((1RG or (4 R,5S)-3-({(3S,5S)-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl}sulfanyl)-5-[(1S,2R)-1-formyl-2-hydroxypropyl]-4-methyl-4,5-dihydro-1H-pyrrole-2-carboxylic acid or ertapenem<b>)</b>) used. Compared to control (which has binding energy score of -11.63 kcal/mol), the compounds showed better binding energy. The binding energy score of LAS_32135590, LAS_34036730 and LAS-51380924 is -12.63 kcal/mol, -12.22 kcal/mol and -12.10 kcal/mol, respectively. Further, the docked snapshot of the lead compounds and control were investigated for stability under time dependent dynamics environment. All the three leads complex and control system showed significant equilibrium (mean RMSD < 3 Å) both in term of intermolecular docked conformation and binding interactions network. Further validation on the complex's stability was acquired from the end-state MMPB/GBSA analysis that observed greater contribution from van der Waals forces and electrostatic energy while less contribution was noticed from solvation part. The compounds were also showed good drug-likeness and are non-toxic and non-mutagenic. In short, the compounds can be used in experimental testing's and might be subjected to structure modification to get better results.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6148-6158"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972039","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}