Journal of Biomolecular Structure & Dynamics最新文献_第8页

Comprehending conformational changes in EmrE, multidrug transporter at different pH: insights from molecular dynamics simulations. 理解多药转运体 EmrE 在不同 pH 值下的构象变化：分子动力学模拟的启示。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2024-01-05 DOI: 10.1080/07391102.2023.2298386

Manpreet Kaur, Preeti Arya, Stanzin Chosyang, Balvinder Singh

{"title":"Comprehending conformational changes in EmrE, multidrug transporter at different pH: insights from molecular dynamics simulations.","authors":"Manpreet Kaur, Preeti Arya, Stanzin Chosyang, Balvinder Singh","doi":"10.1080/07391102.2023.2298386","DOIUrl":"10.1080/07391102.2023.2298386","url":null,"abstract":"EmrE is a small multidrug resistance (SMR) pump of antiparallel topology that confers resistance to a broad range of polyaromatic cations in Escherichia coli. Atomic-level understanding of conformational changes for the selectivity of substrate and transport of a diverse array of drugs through the smallest known efflux pumps is crucial to multi-drug resistance. Therefore, the present study aims to provide insights into conformational changes during the transport through EmrE transporter at different pH. Molecular dynamics simulations have been carried out on the complete structure of EmrE in the absence of substrate. Computational analyses such as secondary structure, principal component, dynamic cross-correlation matrix, and hydrogen bond calculations have been performed. Analysis of MD trajectories in this study revealed pH-dependent interactions that influenced the structural dynamics of EmrE. Notably, at high pH, Glu14 and Tyr60 in both monomers formed electrostatic interactions, while these interactions decreased significantly at a low pH. Interestingly, a kink at helix 3 (H3) and dual open conformation of EmrE at low pH were also observed in contrast to a closed state discerned towards the periplasmic side at high pH. Significant interactions between C-terminal residues and residues at the edge of H1 & Loop1 and H3 & Loop3 were identified, suggesting their role in stabilizing the closed conformation of EmrE at the periplasmic end under high pH conditions. The present study enhances our understanding of EmrE's conformational changes, shedding light on the pH-dependent mechanisms that are likely to impact its function in multi-drug resistance.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3415-3428"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097852","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

Exploration of comprehensive marine natural products database against dengue viral non-structural protein 1 using high-throughput computational studies. 利用高通量计算研究探索针对登革热病毒非结构蛋白 1 的综合性海洋天然产物数据库。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2024-01-02 DOI: 10.1080/07391102.2023.2297006

Basharat Ahmad Bhat, Abdullah Algaissi, Nizar A Khamjan, Tanvir Ul Hassan Dar, Sajad Ahmad Dar, Venkatramanan Varadharajan, Naif A Qasir, Mohtashim Lohani

{"title":"Exploration of comprehensive marine natural products database against dengue viral non-structural protein 1 using high-throughput computational studies.","authors":"Basharat Ahmad Bhat, Abdullah Algaissi, Nizar A Khamjan, Tanvir Ul Hassan Dar, Sajad Ahmad Dar, Venkatramanan Varadharajan, Naif A Qasir, Mohtashim Lohani","doi":"10.1080/07391102.2023.2297006","DOIUrl":"10.1080/07391102.2023.2297006","url":null,"abstract":"Dengue virus (DENV) non-structural protein 1 (NS1) is a versatile quasi-protein essential for the multiplication of the virus. This study applied high-throughput virtual screening (HTVS) and molecular dynamics (MD) simulation to detect the potential marine natural compounds against the NS1 of DENV. The structure of the NS1 protein was retrieved from Protein Data Bank with (PDB ID: 4O6B). Missing residues were added using modeler software. Molecular operating environment (MOE) programme was used to prepare the protein before docking. Virtual screening was performed on PyRx software to identify natural compounds retrieved from Comprehensive Marine Natural Products Database (CMNPD) against the NS1 protein, and best-docked compounds were examined by molecular docking and molecular dynamic (MD) simulation. Out of 31,561 marine compounds, the top 10 compounds showed docking scores lesser than -8.0 kcal/mol. One of the best hit compounds, CMNPD6802, was further analyzed using MD simulation study at 100 nanoseconds and Molecular Mechanics with Generalized Born and Surface Area Solvation (MM/GBSA). Based on its total binding energy, determined using the MM/GBSA approach, CMNPD6802 was ranked first. Its pharmacokinetic properties concerning the target protein NS1 were also evaluated. The results of the MD simulation showed that CMNPD6802 remained in close contact with the protein throughout the activation period, mapped using principal component analysis. These findings suggest that CMNPD6802 could serve as an NS1 inhibitor and may be a potential candidate for treating DENV infections.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3276-3285"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074231","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

Identification of potential inhibitors targeting Ebola virus VP35 protein: a computational strategy. 识别针对埃博拉病毒 VP35 蛋白的潜在抑制剂：一种计算策略。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2023-12-20 DOI: 10.1080/07391102.2023.2294384

Yan-Kun Chen, Reem M Gahtani, Mesfer Al Shahrani, Umme Hani, Fahad M Alshabrmi, Sarfaraz Alam, Hailah M Almohaimeed, Ammar A Basabrain, Muhammad Shahab, Meng-Zhou Xie

{"title":"Identification of potential inhibitors targeting Ebola virus VP35 protein: a computational strategy.","authors":"Yan-Kun Chen, Reem M Gahtani, Mesfer Al Shahrani, Umme Hani, Fahad M Alshabrmi, Sarfaraz Alam, Hailah M Almohaimeed, Ammar A Basabrain, Muhammad Shahab, Meng-Zhou Xie","doi":"10.1080/07391102.2023.2294384","DOIUrl":"10.1080/07391102.2023.2294384","url":null,"abstract":"Ebola virus (EBOV) poses a severe threat as a highly infectious pathogen, causing devastating hemorrhagic fever in both humans and animals. The EBOV virus VP35 protein plays a crucial role in viral replication and exhibits the ability to suppress the host interferon cascade, leading to immune system depletion. As a potential drug target, VP35 protein inhibition holds promise for combating EBOV. To discover new drug candidates, we employed a computer-aided drug design approach, focusing on compounds capable of inhibiting VP35 protein replication. In this connection, a pharmacophore model was generated using molecular interactions between the VP35 protein and its inhibitor. ZINC and Cambridge database were screened using validated pharmacophore model. Further the compounds were filtered based on Lipinski's rule of five and subjected to MD simulation and relative binding free energy calculation. Six compounds manifest a significant docking score and strong binding interaction towards VP35 protein. MD simulations further confirmed the remarkable stability of these six complexes. Relative binding free energy calculations also showed significant ΔG value in the range of -132.3 and -49.3 kcal/mol. This study paves the way for further optimization of these compounds as potential inhibitors of VP35, facilitating subsequent experimental in vitro studies.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2877-2889"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138829947","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

Identification of potential inhibitors targeting yellow fever virus helicase through ligand and structure-based computational studies. 通过配体和基于结构的计算研究，确定针对黄热病病毒螺旋酶的潜在抑制剂。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2023-12-18 DOI: 10.1080/07391102.2023.2294839

Sumera Zaib, Nehal Rana, Hafiz Saqib Ali, Mujeeb Ur Rehman, Nasser S Awwad, Hala A Ibrahium, Imtiaz Khan

{"title":"Identification of potential inhibitors targeting yellow fever virus helicase through ligand and structure-based computational studies.","authors":"Sumera Zaib, Nehal Rana, Hafiz Saqib Ali, Mujeeb Ur Rehman, Nasser S Awwad, Hala A Ibrahium, Imtiaz Khan","doi":"10.1080/07391102.2023.2294839","DOIUrl":"10.1080/07391102.2023.2294839","url":null,"abstract":"Yellow fever is a flavivirus having plus-sensed RNA which encodes a single polyprotein. Host proteases cut this polyprotein into seven nonstructural proteins including a vital NS3 protein. The present study aims to identify the most effective inhibitor against the helicase (NS3) using different advanced ligand and structure-based computational studies. A set of 300 ligands was selected against helicase by chemical structural similarity model, which are similar to S-adenosyl-l-cysteine using infiniSee. This tool screens billions of compounds through a similarity search from in-built chemical spaces (CHEMriya, Galaxi, KnowledgeSpace and REALSpace). The pharmacophore was designed from ligands in the library that showed same features. According to the sequence of ligands, six compounds (29, 87, 99, 116, 148, and 208) were taken for pharmacophore designing against helicase protein. Subsequently, compounds from the library which showed the best pharmacophore shared-features were docked using FlexX functionality of SeeSAR and their optibrium properties were analyzed. Afterward, their ADME was improved by replacing the unfavorable fragments, which resulted in the generation of new compounds. The selected best compounds (301, 302, 303 and 304) were docked using SeeSAR and their pharmacokinetics and toxicological properties were evaluated using SwissADME. The optimal inhibitor for yellow fever helicase was 2-amino-N-(4-(dimethylamino)thiazol-2-yl)-4-methyloxazole-5-carboxamide (302), which exhibits promising potential for drug development.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3031-3048"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803840","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

Phytochemicals as potential inhibitors of interleukin-8 for anticancer therapy: in silico evaluation and molecular dynamics analysis. 植物化学物质作为白细胞介素-8 的潜在抑制剂用于抗癌治疗：硅学评估和分子动力学分析。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2023-12-20 DOI: 10.1080/07391102.2023.2294387

Mohammad Y Alshahrani, Ali Gaithan Alkhathami, Mohammad Ali Abdullah Almoyad, Mohammad Zaki Ahmad, Sourav Mohanto, Wasim Ahmad, Shadma Wahab

{"title":"Phytochemicals as potential inhibitors of interleukin-8 for anticancer therapy: in silico evaluation and molecular dynamics analysis.","authors":"Mohammad Y Alshahrani, Ali Gaithan Alkhathami, Mohammad Ali Abdullah Almoyad, Mohammad Zaki Ahmad, Sourav Mohanto, Wasim Ahmad, Shadma Wahab","doi":"10.1080/07391102.2023.2294387","DOIUrl":"10.1080/07391102.2023.2294387","url":null,"abstract":"Within the realm of soluble factors that have emerged as potential targets for therapeutic intervention, the chemokine interleukin-8 (IL-8) has garnered attention as a potential contributor to treatment responses in various cancer types. The utilization of naturally occurring anticancer compounds for treating cancer patients has shown substantial advancements in survival rates across early and advanced stages of the disease. In silico research findings provide support for the application of phytochemicals as potential inhibitors of IL-8, and phytochemicals exhibiting a high binding free energy and crucial interactions display promising anticancer properties, positioning them as candidates for future drug development. Noteworthy phytochemicals such as IMPHY006634 (Isohydnocarpin), IMPHY007957 (Chitranone) and IMPHY013015 (1-Hydroxyrutaecarpine) were predicted to possess inhibitory activity against IL-8, with calculated energies ranging from -9.9 to -9.1 kcal/mol, respectively. Several hydrogen bonds, including common amino acid residues Lys9 and CYS48, were identified. Molecular dynamics calculations conducted on these potent inhibitors demonstrated their stability throughout a 200 ns simulation, as indicated by metrics such as RMSD, RMSF, Rg, SASA, H-bonds, PCA and FEL analysis. Moreover, PASS analysis and adherence of these natural compounds to drug-likeness rules like Lipinski's further strengthen their candidacy. Considering these calculations and various parameters, these three prominent natural compounds emerge as promising candidates for anti-IL-8 therapy in the management of cancer.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2917-2928"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803945","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

Evaluation of substrate specificity and catalytic promiscuity of Bacillus albus cellulase: an insight into in silico proteomic study aiming at enhanced production of renewable energy. 评估白僵菌纤维素酶的底物特异性和催化杂合性：旨在提高可再生能源生产的硅蛋白质组研究的启示。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2023-12-21 DOI: 10.1080/07391102.2023.2295971

Manish Paul, Amrita Banerjee, Smarajit Maiti, Debanjan Mitra, Pradeep K DasMohapatra, Hrudayanath Thatoi

{"title":"Evaluation of substrate specificity and catalytic promiscuity of Bacillus albus cellulase: an insight into in silico proteomic study aiming at enhanced production of renewable energy.","authors":"Manish Paul, Amrita Banerjee, Smarajit Maiti, Debanjan Mitra, Pradeep K DasMohapatra, Hrudayanath Thatoi","doi":"10.1080/07391102.2023.2295971","DOIUrl":"10.1080/07391102.2023.2295971","url":null,"abstract":"Cellulases are enzymes that aid in the hydrolysis of cellulosic fibers and have a wide range of industrial uses. In the present in silico study, sequence alignment between cellulases from different Bacillus species revealed that most of the residues are conserved in those aligned enzymes. Three dimensional structures of cellulase enzymes from 23 different Bacillus species have been predicted and based on the alignment between the modeled structures, those enzymes have been categorized into 7 different groups according to the homology in their conformational folds. There are two structural contents in Gr-I cellulase namely β1-α2 and β3-α5 loops which varies greatly according to their static position. Molecular docking study between the B. albus cellulase and its various cellulosic substrates including xylanoglucan oligosaccharides revealed that residues viz. Phe154, Tyr258, Tyr282, Tyr285, and Tyr376 of B. albus cellulase are significantly involved in formation stacking interaction during enzyme-substrate binding. Residue interaction network and binding energy analysis for the B. albus cellulase with different cellulosic substrates depicted the strong affinity of XylGlc3 substrate with the receptor enzyme. Molecular interaction and molecular dynamics simulation studies exhibited structural stability of enzyme-substrate complexes which are greatly influenced by the presence of catalytic promiscuity in their substrate binding sites. Screening of B. albus in carboxymethylcellulose (CMC) and xylan supplemented agar media revealed the capability of the bacterium in degrading both cellulose and xylan. Overall, the study demonstrated B. albus cellulase as an effective biocatalyst candidate with the potential role of catalytic promiscuity for possible applications in biofuel industries.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3076-3098"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138829945","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 development of multi-epitope subunit vaccine against lymphatic filariasis. 针对淋巴丝虫病的多表位亚单位疫苗的分子内开发。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2023-12-20 DOI: 10.1080/07391102.2023.2294838

Pratik Singh, Samir Shaikh, Sakshi Gupta, Reeshu Gupta

{"title":"In-silico development of multi-epitope subunit vaccine against lymphatic filariasis.","authors":"Pratik Singh, Samir Shaikh, Sakshi Gupta, Reeshu Gupta","doi":"10.1080/07391102.2023.2294838","DOIUrl":"10.1080/07391102.2023.2294838","url":null,"abstract":"The World Health Organization in 2022 reported that more than 863 million people in 50 countries are at risk of developing lymphatic filariasis (LF), a disease caused by parasitic infection. Immune responses to parasites suggest that the development of a prophylactic vaccine against LF is possible. Using a reverse vaccinology approach, the current study identified Trehalose-6-phosphatase (TPP) as a potential vaccine candidate among 15 reported vaccine antigens for B. malayi. High-ranking B and T-cell epitopes in the Trehalose-6-phosphatase (TPP) were shortlisted using online servers for subsequent analysis. We selected these peptides to construct a vaccine model using I-TASSER and GalaxyRefine server. The vaccine construct showed favorable physicochemical properties, high antigenicity, no allergenicity, no toxicity, and high stability. Structural validation using the Ramachandran plot showed that 98% of the residues were in favorable or mostly allowed regions. Molecular docking and simulation showed a strong binding affinity and stability of the subunit vaccine with toll-like receptor 4 (TLR4). Furthermore, the subunit vaccine showed a strong IgG/IgM response, with the disappearance of the antigen. We propose that our vaccine construct should be further evaluated using cellular and animal models to develop a vaccine that is safe and effective against LF.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3016-3030"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803430","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

Benzothiazole derivatives as p53-MDM2 inhibitors: in-silico design, ADMET predictions, molecular docking, MM-GBSA Assay, MD simulations studies. 作为 p53-MDM2 抑制剂的苯并噻唑衍生物：硅内设计、ADMET 预测、分子对接、MM-GBSA 分析、MD 模拟研究。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2023-12-18 DOI: 10.1080/07391102.2023.2294836

Shridhar Deshpande N, Shivakumar, Udaya Kumar D, Sudeep D Ghate, Sheshagiri R Dixit, Abhimanyu Awasthi, B C Revanasiddappa

{"title":"Benzothiazole derivatives as p53-MDM2 inhibitors: in-silico design, ADMET predictions, molecular docking, MM-GBSA Assay, MD simulations studies.","authors":"Shridhar Deshpande N, Shivakumar, Udaya Kumar D, Sudeep D Ghate, Sheshagiri R Dixit, Abhimanyu Awasthi, B C Revanasiddappa","doi":"10.1080/07391102.2023.2294836","DOIUrl":"10.1080/07391102.2023.2294836","url":null,"abstract":"Breast cancer stands as the most prevalent malignancy among the female populace. One of the pivotal domains in the therapeutic landscape of breast cancer revolves around the precise targeting of the p53-MDM2 inhibitory pathway. The advent of p53-MDM2 inhibition in the context of developing treatments for breast cancer marks a significant stride. In the quest for enhancing the efficacy of p53-MDM2 inhibition against breast cancer, a new series of benzothiazole compounds (B1-B30) was designed through in-silico methodologies in the present work. Using Schrodinger Maestro, the compounds underwent molecular docking assessments against the p53-MDM2 target (PDB: 4OGT). Compared to reference compounds, B25 and B12 exhibited notably elevated glide scores. Extensive in-silico studies, including ADMET and toxicity evaluations, were performed to predict pharmacokinetics, drug likeness, and toxicity. All compounds adhered to Lipinski criteria, signifying favorable oral drug properties. The MM-GBSA analysis indicated consistent binding free energies. Molecular dynamics simulations for B25 over 200 ns assessed complex stability and interactions. In summary, these compounds exhibit potential for future cancer therapy medication development.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2993-3004"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803672","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 simulations show how antibodies may rescue HIV-1 mutants incapable of infecting host cells. 分子动力学模拟显示了抗体如何挽救无法感染宿主细胞的 HIV-1 突变体。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2023-12-18 DOI: 10.1080/07391102.2023.2294835

Dharanish Rajendra, Nikhil Maroli, Narendra M Dixit, Prabal K Maiti

{"title":"Molecular dynamics simulations show how antibodies may rescue HIV-1 mutants incapable of infecting host cells.","authors":"Dharanish Rajendra, Nikhil Maroli, Narendra M Dixit, Prabal K Maiti","doi":"10.1080/07391102.2023.2294835","DOIUrl":"10.1080/07391102.2023.2294835","url":null,"abstract":"High mutation and replication rates of HIV-1 result in the continuous generation of variants, allowing it to adapt to changing host environments. Mutations often have deleterious effects, but variants carrying them are rapidly purged. Surprisingly, a particular variant incapable of entering host cells was found to be rescued by host antibodies targeting HIV-1. Understanding the molecular mechanism of this rescue is important to develop and improve antibody-based therapies. To unravel the underlying mechanisms, we performed fully atomistic molecular dynamics simulations of the HIV-1 gp41 trimer responsible for viral entry into host cells, its entry-deficient variant, and its complex with the rescuing antibody. We find that the Q563R mutation, which the entry-deficient variant carries, prevents the native conformation of the gp41 6-helix bundle required for entry and stabilizes an alternative conformation instead. This is the consequence of substantial changes in the secondary structure and interactions between the domains of gp41. Binding of the antibody F240 to gp41 reverses these changes and re-establishes the native conformation, resulting in rescue. To test the generality of this mechanism, we performed simulations with the entry-deficient L565A variant and antibody 3D6. We find that 3D6 binding was able to reverse structural and interaction changes introduced by the mutation and restore the native gp41 conformation. Viral variants may not only escape antibodies but be aided by them in their survival, potentially compromising antibody-based therapies, including vaccination and passive immunization. Our simulation framework could serve as a tool to assess the likelihood of such resistance against specific antibodies.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2982-2992"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803821","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

Computer aided aptamer selection for fabrication of electrochemical sensor to detect Aflatoxin B₁. 计算机辅助选择适配体，用于制造检测黄曲霉毒素 B1 的电化学传感器。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2024-01-29 DOI: 10.1080/07391102.2024.2308760

Misgana Mengistu Asmare, Chandran Krishnaraj, Sivaprakasam Radhakrishnan, Byoung-Sukh Kim, Soon-Il Yun

{"title":"Computer aided aptamer selection for fabrication of electrochemical sensor to detect Aflatoxin B1.","authors":"Misgana Mengistu Asmare, Chandran Krishnaraj, Sivaprakasam Radhakrishnan, Byoung-Sukh Kim, Soon-Il Yun","doi":"10.1080/07391102.2024.2308760","DOIUrl":"10.1080/07391102.2024.2308760","url":null,"abstract":"Aflatoxin B1 (AFB1) is a naturally occurring toxin produced by Aspergillus flavus and Aspergillus parasiticus. The AFB1 is classified as a potent carcinogen and poses significant health risks both to humans and animals. Early detection of the toxin in post-harvest agricultural products will save lives and promote healthy food production. In this study, stratified docking approach was utilized to screen and identify potential aptamers that can bind to AFB1. ssDNA sequences were acquired from the Mendeley dataset, secondary and tertiary structures were predicted through a series of bioinformatics pipelines. Further, the final DNA tertiary structures were minimized and SiteMap algorithm was used to probe and locate binding cavities. According to the final XP docking result, a 34 nt sequence (5'-ATCCTGTGAGGAATGCTCATGCATAGCAAGGGCT-3') aptamer with a docking score of -5.959 kcal/mol was considered for 200 ns MD Simulation. Finally, the screened DNA-aptamer was immobilized over the gold surface based on Au-S chemistry and utilized for the detection of AFB1. The fabricated DNA-aptamer electrode demonstrated a good analytical performance including wide linear range (1.0 to 1000 ng L-1), detection limit (1.0 ng L-1), high stability, and reproducibility.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3190-3203"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575808","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