Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Molecular docking, molecular dynamics simulation, and enzyme inhibitory studies of vitamin K family members on aldose reductase.","authors":"Sabha Khan, Sumit Thakur, Gurprit Sekhon, Balvinder Singh, Ranvir Singh","doi":"10.1080/07391102.2026.2726982","DOIUrl":"https://doi.org/10.1080/07391102.2026.2726982","url":null,"abstract":"<p><p>Aldose reductase (AR) is a key enzyme in the polyol pathway and plays a major role in the progression of secondary complications of diabetes. Despite extensive efforts to develop natural and synthetic aldose reductase inhibitors (ARIs), most candidates have shown limited clinical efficacy, highlighting the need for more potent and selective inhibitors. In this study, we have systematically evaluated the inhibitory potential of vitamin K family members (vitamin K1, vitamin K2, and vitamin K3) using molecular docking, protein-ligand interaction analysis, molecular dynamics simulations, and enzyme kinetics. Docking analysis predicted that vitamin K2 has the highest binding affinity for AR. Subsequent molecular dynamics simulations revealed that both vitamin K1 and vitamin K2 formed stable complexes with the protein, exhibiting comparable RMSD (∼0.5 Å difference), similar RMSF profiles, and reduced radius of gyration, indicating compact and stable binding. Interaction analysis demonstrated that ligand binding is predominantly driven by hydrophobic interactions, with vitamin K2 forming a higher number of hydrophobic contacts, while vitamin K1 exhibited slightly more hydrogen bonding. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) results further supports stronger binding of vitamin K2 (-56 kcal/mol) compared to vitaminK1 (-51 kcal/mol). Consistent with these findings, enzyme kinetics showed a slightly lower Ki value for vitamin K2 than vitamin K1. In contrast, vitamin K3 failed to maintain stable binding and moved out of the active site during simulation. Overall, the study highlights that hydrophobic interaction-driven stabilization plays a key role in ligand binding, and identifies vitamin K1 and vitamin K2 as promising inhibitors against AR, with vitamin K2 exhibiting more favourable hydrophobic interactions and binding stability.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887620","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":"MHC Class II restricted epitope prediction, crypticity analysis and B cell epitope identification from the proteome of <i>Leishmania donovani</i>.","authors":"Mohammad Kashif, Shweta Sargam, Naidu Subbarao, Partha Pratim Manna","doi":"10.1080/07391102.2026.2725805","DOIUrl":"https://doi.org/10.1080/07391102.2026.2725805","url":null,"abstract":"<p><p><i>Leishmania donovani</i> (<i>L. donovani)</i> causes one of the dreadful diseases called visceral leishmaniasis (VL) affecting millions people in India and some parts of Africa. Several efforts have been made, no effective vaccine is available to date. Immunoinformatics methods play a critical role in predicting potential vaccine candidates. The present study showed extensive analysis of <i>L. donovani</i> proteins for the identification of MHC class II restricted epitopes, cryptic epitopes and B cell epitopes which may help in providing a diverse immune response. A total of 130 epitopes from <i>L. donovani</i> were identified on the basis of their binding towards HLA alleles. These peptides were checked for their hydrophobicity, IFN-γ and IL-10 inducing potentials.A total of 24 peptides were selected for modelling and docking. Molecular dynamics (MD) simulation of the docked complexes with the HLA-DRB1*0101 allele suggests 3 epitopes have the best binding interactions throughout the 100 ns simulation. These epitopes can be considered as potential vaccine candidates and may need further experimental validation before practical application. We also made an attempt to identify cryptic epitopes which remain largely unexplored in the context of <i>L. donovani</i> vaccine design and diagnosis. Out of 24 peptides selected previously, IC₅₀ values of 5 peptides were decreased after the modification with tyrosine residue. Further replacement identified 2-3 modified peptides showing better docking and lesser IC₅₀ values than the original peptides, suggesting cryptic behaviour of the epitopes. Linear and conformation B cell epitopes were also predicted which may suggest importance of these residues for eliciting humoral response.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-23"},"PeriodicalIF":2.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887650","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":"Assessing the pathogenic potential of PIK3CA gene variants in human cancer using a computational approach.","authors":"Rajtilak Detroja, Joydeep Chakraborty, Mandar Kulkarni, Ketankumar Panchal, Neeraj Jain, Mansi Desai","doi":"10.1080/07391102.2026.2726980","DOIUrl":"https://doi.org/10.1080/07391102.2026.2726980","url":null,"abstract":"<p><p>The phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (p110α) is a key lipid kinase encoded by <i>PIK3CA</i> gene that regulates multiple intracellular signaling pathways. The nsSNPs within <i>PIK3CA</i> can alter protein structure and function, thereby influencing cellular processes and increasing susceptibility to various types of cancers. This study aimed to systematically evaluate the consequences of nsSNPs in <i>PIK3CA</i>, and their potential influence on protein behavior and drug interaction. A comprehensive set of in silico tools-including functional impact predictors, structural stability analyzers, conservation-based algorithms, and protein property assessment tools-was employed to investigate the consequences of nsSNPs. Structural modeling was performed to generate native and mutant p110α structures, followed by molecular docking to evaluate how these variants influence binding affinity with Alpelisib. Ten nsSNPs-G363V, R398C, R555K, C769G, F801C, R808W, R808Q, E849K, E849G, and R992Q-were consistently predicted to be deleterious across all functional prediction platforms and were found to affect evolutionarily conserved residues or domains. Among these, six variants (R398C, C769G, F801C, R808W, R808Q, and R992Q) were further predicted to significantly alter physicochemical protein properties. Docking analyses revealed variant-specific shifts in binding affinity. R555K displaying the highest affinity even higher than native and R398C showing lowest affinity toward Alpelisib. These suggest a potentially altered or dysregulated drug-protein interaction. However, the biological benefit or detriment of this shift warrants further experimental evaluation. The findings of this study may enhances our understanding of how <i>PIK3CA</i> variants contribute to predict disease risk and may support future precision-medicine approaches targeting the PI3K pathway.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-19"},"PeriodicalIF":2.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887657","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":"Genome organization and packaging, mutation impacts and quasi-periodic patterns in viral genomes.","authors":"Vladimir R Chechetkin, Vasily V Lobzin","doi":"10.1080/07391102.2026.2719002","DOIUrl":"https://doi.org/10.1080/07391102.2026.2719002","url":null,"abstract":"<p><p>A method described in this publication is able (i) to display features related to the general genome organization and packaging; (ii) to identify explicitly motifs responsible for these features and the distribution of motifs over the genome; the most pronounced motifs can be screened against available databases for further studies; (iii) to assess the impact of mutations; the salient mutations can be tried experimentally and used for genome editing; and (iv) to quantify the information that can be insightful for general studies of molecular evolution of living organisms. The method is based on the transitional genome mapping that may be considered as an extension and adaptation of the general correlation technique and is aimed at displaying significant correlations throughout all genome scales. Combining this method with a correlation entropy as the output variables extends significantly its abilities. The relevant theory was developed and tested for the assessment of statistical significance of the striking features in correlation characteristics. The particular applications are illustrated with the genomes of satellite tobacco mosaic virus, coronaviruses SARS-CoV-2 and SARS-CoV, hepatitis delta virus and viroid representatives from two main families. As shown, the genome editing with salient ordering mutations strengthens significantly the features related to the genome packaging and organization. The relevant underlying quasi-periodic patterns can be reconstructed explicitly. The resulting edited viral sequences can potentially be used for the development of vaccines, drug targeting and for the general studies of underlying molecular mechanisms.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-36"},"PeriodicalIF":2.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874092","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":"Epitope rigidity and long-range coupling shape antigen dynamics in lysozyme-antibody complexes.","authors":"Ayelen Digilio, Luciana Peruzzo, Diego M A Guérin, Eliana K Asciutto","doi":"10.1080/07391102.2026.2726984","DOIUrl":"https://doi.org/10.1080/07391102.2026.2726984","url":null,"abstract":"<p><p>Conformational B-cell epitopes typically rigidify upon antibody binding, while distal antigen regions often become more flexible, yet the mechanistic basis remains unclear. Here we analyze 17 structurally similar lysozyme-antibody complexes using Anisotropic Network Models, Perturbation Response Scanning, and residue-level network analysis. We find that epitope residues are intrinsically low-mobility and act as dynamically influential sites in the unbound antigen, mechanically coupled to distant regions that increase flexibility upon binding. Normal mode analysis reveals that epitopes behave as rigid blocks within global motions, supporting their mechanically cohesive behavior within the antigen structure. These findings suggest that mobility redistribution upon antibody binding arises from pre-existing long-range dynamic coupling encoded in the antigen fold, providing a mechanistic framework linking epitope rigidity, allosteric communication, and global dynamical regulation in lysozyme-Fab complexes.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-20"},"PeriodicalIF":2.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880627","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":"Correction.","authors":"","doi":"10.1080/07391102.2026.2725508","DOIUrl":"https://doi.org/10.1080/07391102.2026.2725508","url":null,"abstract":"","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1"},"PeriodicalIF":2.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840310","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 new approach to study non-covalent interactions of DNA- polymerase complexes in terms of electron density.","authors":"Nadezhda Palko, Krishnamoorthy Gurushankar, Maria Grishina","doi":"10.1080/07391102.2026.2723206","DOIUrl":"https://doi.org/10.1080/07391102.2026.2723206","url":null,"abstract":"<p><p>Interactions between the components of the complex determine the molecular field that ensures complementarity between the contacting structures. In this article, we propose to use AlteQ approach to study DNA polymerase complementarity. The AlteQ approach with good quality describes the experimental electron density which was determined using low temperature high resolution X-ray diffraction. The research methodology was based on constructing electron density 3D maps in the intermolecular contact zone of the complexes, determining the features of the electronic structure, and then establishing the complementarity of the structures to their environment. DNA polymerase complexes with G•C and A•T base pairs were studied. As a result, the zones that determine the complementary field of the complex in terms of electron density were established. It has been established that the environment actively participates in intermolecular interactions, influencing the complementary field. Characteristics that describe the set of intermolecular interactions in the complexes were determined and can be used to assess the binding quality of bases.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828771","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":"Evidence of curvature bias and local POPG recruitment during surface-bound interactions of a cationic peptide with POPC/POPG membrane.","authors":"Lúcio Otávio Nunes","doi":"10.1080/07391102.2026.2723202","DOIUrl":"https://doi.org/10.1080/07391102.2026.2723202","url":null,"abstract":"<p><p>Antimicrobial peptides (AMPs) constitute an important class of antibacterial molecules whose mechanisms of action remain incompletely understood. Among the different stages of peptide-membrane interaction, membrane curvature has been recognized as a key physicochemical event associated with antimicrobial activity. Understanding how this curvature emerges during the early stages of peptide binding is therefore of considerable biological interest. In the present work, coarse-grained molecular dynamics simulations were used to investigate the curvature generated by the cationic peptide Magainin-2 during its surface-bound interaction with an anionic POPC:POPG (3:1) membrane. The results indicate a reproducible bias toward negative membrane curvature that Magainin-2 promotes while remaining in the surface-bound state. Simulations performed in the absence of peptide showed no comparable curvature bias. In peptide-containing systems, modest but consistent POPG recruitment was observed in the regions associated with membrane bending, suggesting a coupling between electrostatic lipid recruitment and local curvature bias. These findings provide computational evidence of membrane organization perturbation in surface-bound peptide interactions, before peptide insertion, contributing to the understanding of the early biophysical events involved in antimicrobial peptide activity.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828804","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":"Vanillin attenuates glycation associated modifications and partially restores iron binding and release properties in human serum transferrin: insights from biophysical and computational studies.","authors":"Bhuvana Kumar, Saraswathi N T","doi":"10.1080/07391102.2026.2720597","DOIUrl":"https://doi.org/10.1080/07391102.2026.2720597","url":null,"abstract":"<p><p>Protein glycation, especially under hyperglycemic conditions observed during diabetes, results in the formation of advanced glycation endproducts (AGEs) as a result of reaction between reducing sugars or dicarbonyls and free amino groups of proteins. The presence of AGEs and the accompanied oxidative stress contribute to the progression and severity of diabetic complications. Transferrin, the major serum glycoprotein involved in transport of iron between cellular sites of absorption and utilization undergoes variable glycation in diabetic patients and <i>in vitro</i> conditions. Glycated transferrin has been attributed with impaired iron binding property under <i>in vitro</i> and <i>in vivo</i> conditions. Here, we report the glycation inhibition observed in methylglyoxal glycated transferrin by vanillin. From our experiments, vanillin showed hindered AGE formation notably in vesperlysine and total AGEs and curtailed advanced oxidation protein product formation. Further glycation induced fibrillation and extent of arginine modification was also reduced in the presence of vanillin. Glycated transferrin did not exhibit enhanced iron binding which was partially restored in the presence of vanillin. Also, glycated transferrin showed marked increase in iron release even at mild acidic conditions while vanillin treatment retained native-like iron release property. The binding of vanillin to transferrin as assessed by fluorescence quenching studies revealed a binding affinity of 0.187 ± 0.04 × 10⁵ M^-1 with one binding site. And <i>in silico</i> molecular dynamics studies showed continuous interaction between vanillin and transferrin and molecular mechanics Poisson Boltzmann surface area binding energy calculations showed the electrostatic energy as the highest contributor. Thereby, vanillin exerts reduced glycation associated effects against glycated transferrin and prevents subsequent oxidative damage and aggregates formation.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-20"},"PeriodicalIF":2.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818629","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":"Transition-metal coordination modulates predicted DNA groove recognition and nucleobase contacts in oligohistidine complexes.","authors":"Soykan Agar, Alparslan Numan Yildiz, Mine Yurtsever","doi":"10.1080/07391102.2026.2723209","DOIUrl":"https://doi.org/10.1080/07391102.2026.2723209","url":null,"abstract":"<p><p>Histidine-rich peptides are widely used in affinity-based purification because imidazole donors can coordinate transition-metal ions. To examine how fixed metal-coordination models may alter the predicted DNA-contacting behavior of a histidine hexamer, a fully in silico comparison was performed using metal-free His₆ and the tri-metal model complexes [Zn₃(His₆)]⁶⁺, [Ni₃(His₆)]⁶⁺, and [Cu₃(His₆)]⁶⁺ against the canonical B-DNA dodecamer 1BNA [d(CGCGAATTCGCG)]. The formulas denote the neutral-terminal/neutral-imidazole computational representation used for docking and molecular dynamics (MD), rather than a claim concerning the dominant solution-phase species. Molecular docking and MD simulations were used to compare predicted groove localization, recurrent nucleobase-associated contacts, hydrogen-bond patterns, relative docking scores, and trajectory-based structural persistence. Within the examined 1BNA model, metal-free His₆ produced a dominant major-groove pose with adenine-associated contacts and a Vina docking score of -8.9 kcal/mol. The tri-metal coordination models produced dominant minor-groove poses with guanine-associated contacts, with relative docking scores of -9.5, -13.5, and -10.8 kcal/mol for the Zn(II), Ni(II), and Cu(II) models, respectively. The Ni(II)- and Cu(II)-containing models also displayed lower RMSD levels than the metal-free complex over the sampled trajectories. These observations are restricted to the defined computational models and the 1BNA sequence; they do not establish experimental binding affinities, universal nucleobase selectivity, or solution-phase metal speciation. The work provides a hypothesis-generating comparison that may guide future experimental investigation of metal-coordinated oligohistidine-DNA interactions.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-11"},"PeriodicalIF":2.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828762","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}