Journal of Biomolecular Structure & Dynamics最新文献

Molecular insights into particular mutations impact on Taq polymerase dynamics and structure: a molecular dynamics simulation study. 分子洞察特定突变对Taq聚合酶动力学和结构的影响：分子动力学模拟研究。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-07-25 DOI: 10.1080/07391102.2025.2524436

Seddigheh Borhani, Seyed Shahriar Arab

{"title":"Molecular insights into particular mutations impact on Taq polymerase dynamics and structure: a molecular dynamics simulation study.","authors":"Seddigheh Borhani, Seyed Shahriar Arab","doi":"10.1080/07391102.2025.2524436","DOIUrl":"https://doi.org/10.1080/07391102.2025.2524436","url":null,"abstract":"Taq DNA polymerase (Taq pol), a useful enzyme in biotechnology, has been the subject of an extensive investigation to create enzymes with altered characteristics, notably the enhancement of Taq pol's thermostability, But the demand for such enzymes remains unmet. In this study, we aimed to introduce several mutations to the Taq pol structure to improve its structural stability. We combined the sequence-based and structure-based rational design mutagenesis techniques to incorporate five mutations into the Taq pol structure. The impact of the mutations on the enzyme was examined by the utilization of molecular dynamics simulations. All mutant enzymes exhibited a more compact structure and a greater abundance of internal hydrogen bonds and secondary structure contents. While the mutants TaqG389E and TaqS290K|A353K|L365E|N384E|G389E demonstrated the least structural dynamics, the other mutant enzymes displayed higher or comparable flexibility compared to the wild-type. Furthermore, a reduction in the distance between mutation positions and neighboring charged amino acids was observed in most of the mutant structures. The enhancement of non-bonded interactions resulted in the evaluation of structure stability. Based on this fact, all of the suggested mutations had positive effects on the stability of the Taq pol structure. Additionally, a decrease in structural flexibility led to a more stable structure; hence, TaqG389E and TaqS290K|A353K|L365E|N384E|G389E mutants were considered more stable compared to wild-type Taq pol. The mutants TaqG389E and TaqS290K|A353K|L365E|N384E|G389E exhibited excellent performance in terms of reduced structural flexibility, evaluated internal hydrogen bonds, and the capacity to establish multiple stabilizable interactions when compared to the wild-type.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707542","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}

引用次数: 0

Exploring the molecular interaction of celastrol and HMGB1 by multi-spectra analysis. 多光谱分析探讨雷公藤红素与HMGB1的分子相互作用。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-07-24 DOI: 10.1080/07391102.2025.2530041

Yanyan Meng, Xuewa Jiang, Richa Raj, Pingping Shen, Jian Zhang

{"title":"Exploring the molecular interaction of celastrol and HMGB1 by multi-spectra analysis.","authors":"Yanyan Meng, Xuewa Jiang, Richa Raj, Pingping Shen, Jian Zhang","doi":"10.1080/07391102.2025.2530041","DOIUrl":"https://doi.org/10.1080/07391102.2025.2530041","url":null,"abstract":"As damage-associated molecular patterns (DAMPs), the high mobility group box 1 (HMGB1) mediates the transmission of intercellular damage, inflammatory signals and plays a key role in pathological processes such as aseptic inflammation, autoimmune diseases and cancer. Celastrol, a natural product extracted from Tripterygium wilfordii Hook.f, exerts a neuroprotective effect by binding to HMGB1 in cerebral ischemia-reperfusion injury. To explore the binding characteristics between celastrol and HMGB1, surface plasmon resonance (SPR), dynamic light scattering (DLS) and multi-spectral technology, including fluorescence spectroscopy and circular dichroism (CD) spectra, were applied. Molecular docking as well as molecular dynamic (MD) simulation were also performed to predict the binding poses of celastrol and HMGB1. The SPR results showed that the KD value of celastrol and HMGB1 was 5.57 × 10-5 M. In fluorescence spectroscopy, the binding of celastrol can dose-dependently quench the endogenous fluorescence of HMGB1, and the quenching type is static quenching. Moreover, celastrol can also reduce the content of α-helix and enhance the random coil content of HMGB1, which could increase its particle size. Molecular docking celastrol was engaged in interactions with the amino acids Lys95, Arg104 and Ala133, resulting in the formation of multiple hydrogen bonds within the length of 1.8-2.0 Å. The main forces involved were electrostatic interaction, hydrophobic interaction and hydrogen bonds. The MD simulation further showed that a stable complex was formed between HMGB1 and celastrol. The in vitro biological evaluation showed that celastrol could inhibit NO release in the HMGB1-induced RAW264.7 inflammatory cell model with an IC50 value of 0.89 μM. Celastrol could bind to HMGB1 and slightly change its secondary structure and spatial conformation, subsequently affecting its pro-inflammatory function.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698668","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}

引用次数: 0

In silico and NMR studies on pharmaceutical compounds with therapeutic action against Myasthenia Gravis. 对重症肌无力有治疗作用的药物化合物的硅和核磁共振研究。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-07-24 DOI: 10.1080/07391102.2025.2532095

Errikos Petsas, Eleftherios Massios, Nikitas Georgiou, Antigoni Cheilari, Panagiotis Konstantinos Papadimitriou, Margarita Georgia Kakava, Ektoras Vasileios Apostolou, Ioannis Angelonidis, Nikolaos Eleftheriadis, Demeter Tzeli, Thomas Mavromoustakos

{"title":"In silico and NMR studies on pharmaceutical compounds with therapeutic action against Myasthenia Gravis.","authors":"Errikos Petsas, Eleftherios Massios, Nikitas Georgiou, Antigoni Cheilari, Panagiotis Konstantinos Papadimitriou, Margarita Georgia Kakava, Ektoras Vasileios Apostolou, Ioannis Angelonidis, Nikolaos Eleftheriadis, Demeter Tzeli, Thomas Mavromoustakos","doi":"10.1080/07391102.2025.2532095","DOIUrl":"https://doi.org/10.1080/07391102.2025.2532095","url":null,"abstract":"Myasthenia Gravis, a chronic autoimmune disease, is primarily treated with acetylcholinesterase inhibitors. However, these drugs are not specific, and their mechanism of action against the disease has not been elucidated. They have a propensity to act on different targets, and their therapeutic action is symptomatic. For this reason, we have studied the interactions of commercially available drugs against Myasthenia Gravis to various enzyme targets to examine if there is any selectivity in their action and possibly to reveal any potential use for other diseases. In particular, the Computational Chemistry programs, AutoDock and Maestro, were used to assess the binding of azathioprine, prednisone, and pyridostigmine to different classes of enzymes, such as: cyclooxygenases (COX-1, COX-2), monoamine oxidases (MAO-A, MAO-B), angiotensin receptors (AT1, AT2), and lipoxygenases (LOX-1, 5-LOX). Molecular Dynamics simulations were employed to further analyze the stability and interactions of the most effective compounds. Using in silico platforms it was found that these drugs are not toxic, they do not produce unwanted adverse eaffects, and that pyridostigmine seems to be the best compound according to the ADME results. Additionally, Saturation Transfer Difference NMR experiments were carried out and confirmed the binding of azathioprine to LOX-5 at both the molecular and atomic levels. The in vitro evaluation of azathioprine and prednisone also revealed important inhibition of human 15-LOX-1 over general lipoxygenase activity. Finally, it was found that these drugs have potential for use in various biological and pharmacological applications such as CNS drugs.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-19"},"PeriodicalIF":2.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698634","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}

引用次数: 0

Computational and structural analysis of FliC-TLR5 interaction, a key for immunity against Clostridium chauvoei infection. flil - tlr5相互作用的计算和结构分析，这是对chauvoei梭状芽胞杆菌感染免疫的关键。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-07-22 DOI: 10.1080/07391102.2025.2530064

Pillenahalli Sadashivappa Pooja, Anand Shirisha, Suresh Bindu, Venkatesan Vikkram, Mandrira Ramakrishna Namrutha, Roopa Anandamurthy Hemanth, Mohammed Mudassar Chanda, Sathish Bhadravati Shivachandra

{"title":"Computational and structural analysis of FliC-TLR5 interaction, a key for immunity against Clostridium chauvoei infection.","authors":"Pillenahalli Sadashivappa Pooja, Anand Shirisha, Suresh Bindu, Venkatesan Vikkram, Mandrira Ramakrishna Namrutha, Roopa Anandamurthy Hemanth, Mohammed Mudassar Chanda, Sathish Bhadravati Shivachandra","doi":"10.1080/07391102.2025.2530064","DOIUrl":"https://doi.org/10.1080/07391102.2025.2530064","url":null,"abstract":"Deciphering intricacies of the immune response to Clostridium chauvoei is critical for developing effective vaccines and therapeutic strategies against blackleg in ruminants. Flagellin (FliC), a key virulence factor, facilitates bacterial motility and acts as a pathogen-associated molecular pattern (PAMP), eliciting host immune responses through Toll-like receptor 5 (TLR5). Building on this, a computational analysis of FliC from diverse C. chauvoei strains was conducted to identify conserved immunogenic regions and assess its interaction with TLR5 in Bos taurus and Ovis aries. Multiple sequence alignment revealed conserved N- and C-terminal domains flanking a hypervariable central region. Immuno-informatic analysis predicted 13 B-cell epitopes, two of which were highly conserved and represent promising candidates for cross-protective vaccine development. Structural models of FliC and TLR5 receptors were predicted and validated for reliability. Subsequent docking and molecular dynamics simulations demonstrated a stronger and more stable interaction between FliC and Bos taurus TLR5, supported by favourable binding energy (-69.85 ± 3.70 kcal/mol), highlighting species-specific immune recognition. These findings establish FliC as a potential subunit vaccine candidate and provide insights into host-specific immune responses, contributing to the development of flagellin based immuno-therapeutics to combat blackleg disease in ruminants.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-20"},"PeriodicalIF":2.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682655","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}

引用次数: 0

α-Mangostin conjugated amino acids as estrogen receptor alpha (ERα) inhibitor. α-山竹苷缀合氨基酸作为雌激素受体α (ERα)抑制剂。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-07-11 DOI: 10.1080/07391102.2025.2521413

Hanggara Arifian, Rani Maharani, Sandra Megantara, Amirah Mohd Gazzali, Muchtaridi Muchtaridi

{"title":"α-Mangostin conjugated amino acids as estrogen receptor alpha (ERα) inhibitor.","authors":"Hanggara Arifian, Rani Maharani, Sandra Megantara, Amirah Mohd Gazzali, Muchtaridi Muchtaridi","doi":"10.1080/07391102.2025.2521413","DOIUrl":"https://doi.org/10.1080/07391102.2025.2521413","url":null,"abstract":"α-Mangostin is a xanthone-derived compound, which can be isolated from the mangosteen's pericarps. It exhibits potential as an anticancer agent and is known to suppress the growth of breast cancer cells. One of the known drawbacks of utilizing α-mangostin is its low bioavailability and to overcome this problem, structure modifications was performed by conjugating α-mangostin with specific amino acids. Molecular modeling of α-mangostin conjugates with amino acids has been systematically conducted. The pharmacophore modeling results using the Ligand-Based Drug Design approach showed that all conjugates conform to the pharmacophore features. The docking simulation results highlight the ability of Am1Leu conjugate to demonstrate interactions with estragon receptor-α (ERα) with a binding energy of -10.74 kcal/mol. Further analysis through molecular dynamics simulations over a 200 ns timeframe supports the efficacy of Am1Leu against ERα. According to the MMPBSA method for molecular dynamics modeling, the binding affinities of 4-hydroxytamoxifen (ΔG Total = -53.25 kcal/mol) and Am1Leu (ΔG Total = -53.33 kcal/mol) were found to be comparable. This suggests that Am1Leu (leucine at C6 hydroxy group) exhibits a similar binding affinity towards ERα as 4-hydroxytamoxifen. The evidence obtained from this study suggested the viability of Am1Leu as a candidate with a good affinity towards ERα for the targeting of breast cancer.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608514","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}

引用次数: 0

Study of active ingredients and potential mechanisms of Yin-Chen-Si-Ni decoction in treating cholestatic jaundice based on UHPLC-Q-Exactive Orbitrap MS, network pharmacology, and molecular docking. 基于UHPLC-Q-Exactive Orbitrap MS、网络药理学、分子对接研究银陈四逆汤治疗胆汁淤积性黄疸的有效成分及作用机制

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-07-08 DOI: 10.1080/07391102.2025.2521410

Yanru Liu, Jiayi Zheng, Gongjun Yang, Fang Feng

{"title":"Study of active ingredients and potential mechanisms of Yin-Chen-Si-Ni decoction in treating cholestatic jaundice based on UHPLC-Q-Exactive Orbitrap MS, network pharmacology, and molecular docking.","authors":"Yanru Liu, Jiayi Zheng, Gongjun Yang, Fang Feng","doi":"10.1080/07391102.2025.2521410","DOIUrl":"https://doi.org/10.1080/07391102.2025.2521410","url":null,"abstract":"Yin-Chen-Si-Ni decoction (YCSND), as a common therapeutic practice recommendation in traditional Chinese medicine (TCM), has been applied to the management of cholestatic jaundice (CJ) syndromes. However, the effective components of YCSND and how this works have not been thoroughly documented. To elucidate the chemical map of YCSND in this work, the UHPLC-Q-Exactive Orbitrap MS analysis was carried out. Following the screening of chemical compositions for drug-likeness and oral bioavailability, multiple databases were consulted to obtain the targets of YCSND and CJ. The multiple networks were then studied to identify the core targets, effective components, and signaling pathways. Interactions between putative effective substances and important targets were assessed using molecular docking. The ideal core protein-compound complexes discovered by molecular docking were further validated using molecular dynamic simulations (MDS). According to this technique, 37 of the 172 chemical compounds that were found in the YCSND samples met the requirements for medication absorption. Network pharmacological analysis demonstrated that YCSND exhibited anti-CJ effects through quercetin, luteolin, kaempferol, glabridin, morin, and isorhamnetin acting on STAT3, EGFR, SRC, HSP90AA1, PIK3R1, ESR1, IL6, and TNF by regulating the PI3K-Akt, TNF, and MAPK signaling pathway. The anti-CJ mechanisms of YCSND might involve anti-oxidation, anti-inflammatory, apoptosis, and bile acid transport. Finally, molecular docking and MDS demonstrated that these core proteins had strong binding ability with effective components. Our integrated approach may offer methodological guidelines for investigating possible mechanisms and material foundation of TCM.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-19"},"PeriodicalIF":2.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584026","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}

引用次数: 0

Synthesis, biological evaluation, and molecular modelling studies of novel Ethyl 3-benzoyl-6,8-dichloroindolizine-1-carboxylates against malaria vector Anopheles arabiensis. 新型3-苯甲酰-6,8-二氯吲哚嗪-1-羧酸乙酯抗疟媒介阿拉伯按蚊的合成、生物学评价及分子模型研究。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-07-04 DOI: 10.1080/07391102.2025.2527142

Gayakvad Sunitaben Mangubhai, Pran Kishore Deb, Gourav Rakshit, Priya Tiwari, Viresh Mohanlall, Raquel M Gleiser, Mohamed A Morsy, Katharigatta N Venugopala, Sandeep Chandrashekharappa

{"title":"Synthesis, biological evaluation, and molecular modelling studies of novel Ethyl 3-benzoyl-6,8-dichloroindolizine-1-carboxylates against malaria vector Anopheles arabiensis.","authors":"Gayakvad Sunitaben Mangubhai, Pran Kishore Deb, Gourav Rakshit, Priya Tiwari, Viresh Mohanlall, Raquel M Gleiser, Mohamed A Morsy, Katharigatta N Venugopala, Sandeep Chandrashekharappa","doi":"10.1080/07391102.2025.2527142","DOIUrl":"https://doi.org/10.1080/07391102.2025.2527142","url":null,"abstract":"A series of novel dichloroindolizine carboxylate analogues (4a-n) have been prepared by using 3,5-dichloropyridine, and substituted phenacyl bromide with electron-deficient acetylene via a [3 + 2] cycloaddition reaction. This methodology features a reaction that is free from transition metal or catalyst, providing an eco-friendly synthesis for developing dichloroindolizines. All the synthesized products (4a-n) were characterized by 1H NMR,13C NMR, and HRMS spectroscopic techniques. All the final compounds were evaluated for larvicidal activity using Temephos as the reference standard against Anopheles arabiensis. Compound 4c exhibited the highest larval mortality of 96.67% after 48 h of exposure, which is on par with the positive control, Temephos. Compounds 4e, 4i, 4j, and 4m were moderately toxic, resulting in 70.00%, 74.44%, 73.33%, and 70.00% mortality, respectively, after 48 h of exposure. To validate the biological activity and elucidate a plausible mechanism of action of these compounds molecular docking studies were carried out against six known antimalarial targets. Potential compounds 4c and 4e showed significant binding affinities and correlation of larvicidal activity against the targets calcium-dependent protein kinase-1 (4JBV) and acetylcholinesterase from malaria vector (6ARY). Molecular dynamics studies (300 ns) further supported the stability of these compounds 4c and 4e inside the binding pockets of 4JBV and 6ARY, as evidenced by the RMSD, RMSF, H-bonding, and other stable interactions. Therefore, these novel indolizines can be considered as potential multi-targeting lead molecules for further optimization to combat malaria.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560155","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}

引用次数: 0

A comparison of anticoagulant activities of warfarin and its imino-derivatives: in silico molecular docking evaluation. 华法林及其亚胺衍生物抗凝血活性的比较：硅分子对接评价。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-07-03 DOI: 10.1080/07391102.2025.2527896

Imran Ali, Marwa Ghouizi, Khaled Sekkoum, Nasser Belboukhari, Khairedine Kraim, Marcello Locatelli

{"title":"A comparison of anticoagulant activities of warfarin and its imino-derivatives: in silico molecular docking evaluation.","authors":"Imran Ali, Marwa Ghouizi, Khaled Sekkoum, Nasser Belboukhari, Khairedine Kraim, Marcello Locatelli","doi":"10.1080/07391102.2025.2527896","DOIUrl":"https://doi.org/10.1080/07391102.2025.2527896","url":null,"abstract":"A comparison of anticoagulant activities of the enantiomers of warfarin and its imino derivatives was predicted by in silico molecular docking evaluation. The properties prediction results were calculated using the famous online server SwissADME, which showed that the studied derivatives fulfilled five Lipinski's rule of five. These results indicate that these compounds are expected to be well absorbed with good permeability and bioavailability. Furthermore, the anticoagulant activities of warfarin and its imino derivatives were investigated against vitamin K epoxide reductase using molecular docking. In this study, Molegro was the tool of choice where the new imino derivatives of warfarin have been docked within vitamin K epoxide reductase (VKOR) with PDBID: 3kp9. The docking results clearly indicated that the studied imino derivatives of warfarin have lower binding affinities, compared to warfarin with -7.4 and -8.08 kcal/mol for MNR and MAR derivatives, respectively. S-derivatives of ONS, MNS, OAS, and MAS showed to lower binding affinities with values of -5.65, -6.22, -5.26, -5.41 kcal/mole for ONS, MNS, OAS, MAS, respectively. Thus, all the studied ligands showed lower rerank scores ranged from -85.677 to -109.374, which indicated their stable bonds toward VKOR and higher biological activity. Overall, the MAR-VKOR complex was more potent derivative with a lower rerank score of -106.721 and binding affinity -8.08 kcal/mol respectively. The derivatives have shown both H bonds and steric interactions with the protein amino acids, which reflect their ability to be promiscuous the drug candidates. These findings are important to pan the experimental results for the imino derivatives.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553683","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}

引用次数: 0

Mechanisms of azithromycin resistance in Salmonella Typhi: molecular insights from dynamics behavior to clinical implications. 伤寒沙门氏菌阿奇霉素耐药机制：从动力学行为到临床意义的分子见解。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-07-03 DOI: 10.1080/07391102.2025.2524407

Syeda Farishta, Rani Faryal, Muhammad Waqas, Muhammad Ali, Rizwan Uppal, Muhammad Salman, Zurva Ashraf, Asaad Khalid, Ajmal Khan

{"title":"Mechanisms of azithromycin resistance in Salmonella Typhi: molecular insights from dynamics behavior to clinical implications.","authors":"Syeda Farishta, Rani Faryal, Muhammad Waqas, Muhammad Ali, Rizwan Uppal, Muhammad Salman, Zurva Ashraf, Asaad Khalid, Ajmal Khan","doi":"10.1080/07391102.2025.2524407","DOIUrl":"https://doi.org/10.1080/07391102.2025.2524407","url":null,"abstract":"The widespread use of azithromycin during the COVID-19 pandemic has likely contributed to the increased resistance of Salmonella Typhi to this antibiotic. This study focuses on the extensive drug resistance (XDR) of Salmonella Typhi in Pakistan, analyzing 11,916 suspected typhoid fever cases, with 424 confirmed as Salmonella Typhi and Paratyphi A. Through antimicrobial susceptibility tests and PCR-based Sanger sequencing, an R717L mutation in the AcrB gene was identified, signalling the emergence of azithromycin resistance. This mutation was notably prevalent among XDR Salmonella Typhi isolates, with a high detection of blaCTX-M gp 1 (93%), followed by blaCTX-M 2 (87%) and blaTEM (81%). Detailed analysis revealed that the R717L mutation significantly alters the AcrB protein's interaction with azithromycin, evidenced by lower docking scores and reduced critical interactions, thus diminishing the antibiotic's affinity. Molecular Dynamics (MD) simulations further demonstrated that this mutation induces considerable structural changes in AcrB, impacting its stability and conformation. Additionally, binding free energy calculations showed decreased binding affinity of azithromycin to the mutated AcrB protein. These findings underscore the critical role of the R717L mutation in conferring drug resistance and highlight the urgent need for developing new antibiotic strategies to combat this growing threat. The evolution of azithromycin resistance in XDR Salmonella Typhi underscores the importance of cautious antibiotic use and the necessity for ongoing surveillance and research to inform effective typhoid fever treatment protocols.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-20"},"PeriodicalIF":2.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553684","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}

引用次数: 0

Molecular dynamics simulation of the aggregation and folding mechanism of α-synuclein 47-56 in core peptide fragments induced by α-synuclein pentamer template. α-synuclein五聚体模板诱导α-synuclein 47-56在核心肽片段聚集折叠机制的分子动力学模拟。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-07-03 DOI: 10.1080/07391102.2025.2528927

Ruijuan Liu, Xuewei Liu

{"title":"Molecular dynamics simulation of the aggregation and folding mechanism of α-synuclein 47-56 in core peptide fragments induced by α-synuclein pentamer template.","authors":"Ruijuan Liu, Xuewei Liu","doi":"10.1080/07391102.2025.2528927","DOIUrl":"https://doi.org/10.1080/07391102.2025.2528927","url":null,"abstract":"The misfolding of intrinsically disordered α-synuclein protein, which can form β-sheet-rich fibrillar amyloid structures, is closely associated with Parkinson's disease (PD). The peptide α-synuclein 47-56 has been identified as the toxic core of α-synuclein and plays a pivotal role in the aggregation and misfolding processes of this protein. Investigating the template induction behavior of this peptide is crucial for elucidating the molecular mechanisms underlying α-synuclein misfolding and aggregation. To explore the molecular mechanism of the peptide α-synuclein 47-56, guided by the α-synuclein pentamer template, we conducted a 400 ns molecular dynamics simulation. In this simulation, the peptide α-synuclein 47-56 was positioned on both sides of the α-synuclein pentamers. Our results demonstrate distinct elongation characteristics of the peptide α-synuclein 47-56 on the two sides of the pentamer. The β-sheet structure readily formed on the left side of the α-synuclein pentamer, facilitating template induction. In contrast, the formation of β-sheet secondary structures was hindered on the right side of the α-synuclein pentamer. Furthermore, our analysis reveals that hydrogen bonding, electrostatic interactions, and van der Waals forces between the α-synuclein pentamer and monomer are crucial for β-sheet extension. Notably, we identified the α-synuclein 49-53 region as a key peptide segment in this process.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553685","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}

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