Journal of Biomolecular Structure & Dynamics最新文献_第4页

Design, spectroscopic characterization, in silico and in vitro cytotoxic activity assessment of newly synthesized thymol Schiff base derivatives. 新合成的百里酚席夫碱衍生物的设计、光谱表征、硅学和体外细胞毒性活性评估。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-01 Epub Date: 2024-01-10 DOI: 10.1080/07391102.2024.2301747

Eyüp Başaran, Reşit Çakmak, Dicle Sahin, Semiha Köprü, Burçin Türkmenoğlu, Senem Akkoc

{"title":"Design, spectroscopic characterization, in silico and in vitro cytotoxic activity assessment of newly synthesized thymol Schiff base derivatives.","authors":"Eyüp Başaran, Reşit Çakmak, Dicle Sahin, Semiha Köprü, Burçin Türkmenoğlu, Senem Akkoc","doi":"10.1080/07391102.2024.2301747","DOIUrl":"10.1080/07391102.2024.2301747","url":null,"abstract":"Cancer is a global public health problem affecting millions of people every year. New anticancer drug candidates are needed to overcome the resistance to drugs used in the treatment of various types of cancer. In this study, two new series of benzenesulfonate-based thymol derivatives (14-19 and 20-25) were synthesized for the first time as promising chemotherapeutic agents and characterized using FT-IR, 1D NMR (1H- and 13C-NMR, APT, DEPT 135), 2D NMR (HETCOR and HMBC), and elemental analysis (CHNS). Antiproliferative activity of the molecules was determined against cancer cell lines, namely, the human lung adenocarcinoma cell line (A549) and the colorectal adenocarcinoma cell line (DLD-1), using MTT method for both 48 and 72 h. Compounds (14-25) showed cytotoxic activities against A549 with IC50 values ranging from 9.98 to 81.83 μM, respectively, compared to cisplatin (6.65 μM). These compounds exhibited antiproliferative activities against DLD-1 cancer cells at concentrations ranging from 4.29 to 53.62 μM, respectively, compared to cisplatin (9.91 μM). Especially, compound 16 displayed significant cytotoxicity on A549 and DLD-1 cancer cells with IC50 values of 9.98 and 10.75 μM, respectively. Finally, molecular docking studies were performed with Bcl-2, VEGFR-2, EGFR, and HER2 targets using the Schrödinger 2021-2 Maestro Glide program. The binding energy values and binding interactions of compounds 16 and 22 were determined to be the result of their interactions with these targets. Schrödinger 2021-2 Qikprop wizard drug similarity ratios and ADME prediction of all compounds 14-25 were also calculated.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4111-4124"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403031","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

Bitter taste receptors establish a stable binding affinity with the SARS-CoV-2-spike 1 protein akin to ACE2. 苦味受体与类似 ACE2 的 SARS-CoV-2-spike 1 蛋白建立了稳定的结合亲和力。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-01 Epub Date: 2024-01-08 DOI: 10.1080/07391102.2023.2300128

Senthil Arun Kumar, C Selvaa Kumar, Norine Dsouza

{"title":"Bitter taste receptors establish a stable binding affinity with the SARS-CoV-2-spike 1 protein akin to ACE2.","authors":"Senthil Arun Kumar, C Selvaa Kumar, Norine Dsouza","doi":"10.1080/07391102.2023.2300128","DOIUrl":"10.1080/07391102.2023.2300128","url":null,"abstract":"COVID-19 is caused by the highly contagious SARS-CoV-2 virus, which originated in Wuhan, China, resulting in the highest worldwide mortality rate. Gustatory dysfunction is common among individuals infected with the Wild-type Wuhan strain. However, there are no reported cases of gustatory dysfunction among patients infected with the mutant delta variant. The reason behind this remains elusive to date. This in-silico-based study aims to unravel this clinical factor by evaluating the overall binding affinity of predominant bitter taste receptors associated with gustatory function (T2R-4, 10, 14, 19, 31, 38, 43, and 46) with the Receptor Binding Domain (RBD) of spike 1 (S1) protein of Wuhan (Wild)/delta-SARS-CoV-2 (mut1-T478K; mut2-E484K) variants. Based on docking and MM/PBSA free binding energy scores, the Wild RBD showed a stronger interaction with T2R-46 compared to the ACE2 protein. However, both delta variant mutants (mut1 and mut2) could not establish a stronger binding affinity with bitter taste receptor proteins, except for T2R-43 against mut1. In conclusion, the delta variants could not establish a better binding affinity with bitter taste receptors, contradicting the Wild variant that determines the severity of gustatory dysfunction among patients exposed to the delta and Wild SARS-CoV-2 variants. The study's inference also proposes T2R-46 as an alternate binding receptor target for RBD-S1 of Wild SARS-CoV-2, augmenting its virulence in all functional organs with compromised α-gustducin interaction and bitter sensitization. This in-silico-based study needs further wet-lab-based validation for a better understanding of the role of T2R-46-based viral entry in the human host.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3845-3858"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377683","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

QM/MM investigation of the discriminatory pre-transfer editing mechanism operated by Lysyl-tRNA synthetase. 赖氨酰-tRNA 合成酶的鉴别转移前编辑机制的 QM/MM 研究。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-01 Epub Date: 2024-01-10 DOI: 10.1080/07391102.2023.2301054

Bogdan F Ion, Mohamed M Aboelnga, James W Gauld

{"title":"QM/MM investigation of the discriminatory pre-transfer editing mechanism operated by Lysyl-tRNA synthetase.","authors":"Bogdan F Ion, Mohamed M Aboelnga, James W Gauld","doi":"10.1080/07391102.2023.2301054","DOIUrl":"10.1080/07391102.2023.2301054","url":null,"abstract":"Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that remarkable facilitate the aminoacylation process during translation. With a high fidelity, the mischarged tRNA is prevented through implementing pre- and post-transfer proofreading mechanisms. For instance, Lysine-tRNA synthetase charges the native substrate, lysine, to its cognate tRNA. In spite of the great structural similarity between lysine to the noncognate and toxic ornithine, with the side chain of lysine being only one methylene group longer, LysRS is able to achieve this discrimination with a high efficiency. In this work, the hybrid quantum mechanics/molecular mechanics (QM/MM) investigation was applied to probe the pre-transfer editing mechanism catalyzed by lysyl-tRNA synthetase to reject the noncognte aminoacyl, L-ornityl (Orn), compared to the cognate substrate, L-lysyl. Particularly, the self-cyclization pre-transfer editing mechanism was explored for the two substrates. The substrate-assisted self-cyclization editing of Orn-AMP, where its phosphate moiety acts as the catalytic base, is found to be the rate-determining step with an energy barrier of 101.2 kJ mol-1. Meanwhile, the corresponding rate-limiting pathway for the native Lys-AMP lies at 140.2 kJ mol-1. This observation clearly indicated the infeasibility of this catalytic scenario in the presence of the native substrate. Interestingly, a thermodynamically favorable cyclic product of -92.9 kJ mol-1 with respect to the aminoacyl reactant complex demonstrated evidence of a successful pre-transfer editing. This reaction resulted in the discharge of the on-cognate -ornithine derivative from LysU's active site. These valuable mechanistic insights are valuable to enrich our knowledge of this extremely efficient and specific catalytic machinery of LysRS.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4004-4012"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403047","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

Copper(II)-photocatalyzed Hydrocarboxylation of Schiff bases with CO₂: antimicrobial evaluation and in silico studies of Schiff bases and unnatural α-amino acids. Copper(II)-photocatalyzed Hydrocarboxylation of Schiff bases with CO2: antimicrobial evaluation and in silico studies of Schiff bases and unnatural α-amino acids.

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-01 Epub Date: 2024-01-08 DOI: 10.1080/07391102.2024.2301765

Allen T Gordon, Eric C Hosten, Sandy van Vuuren, Adeniyi S Ogunlaja

{"title":"Copper(II)-photocatalyzed Hydrocarboxylation of Schiff bases with CO2: antimicrobial evaluation and in silico studies of Schiff bases and unnatural α-amino acids.","authors":"Allen T Gordon, Eric C Hosten, Sandy van Vuuren, Adeniyi S Ogunlaja","doi":"10.1080/07391102.2024.2301765","DOIUrl":"10.1080/07391102.2024.2301765","url":null,"abstract":"We synthesized and characterized two copper(II) complexes: [CuL2Cl]Cl and [CuL'2Cl]Cl, where L = 2,2'-bipyridine and L' = 4,4'-dimethyl-2,2'-bipyridine. We evaluated their photocatalytic hydrocarboxylation properties on a series of synthesized Schiff bases (SBs): (E)-1-(4-((5-bromo-2-hydroxybenzylidene)amino)phenyl)ethanone (SB1), (E)-N-(4-(dimethylamino)benzylidene)benzo[d]thiazol-2-amine (SB2), (E)-4-Bromo-2-((thiazol-2-ylimino)methyl)phenol (SB3), and (E)-4-((5-bromo-2-hydroxybenzylidene)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (SB4). Under mild photocatalytic reaction conditions (room temperature, 1 atm CO2, 30-watt Blue LED light), the derivatives of α-amino acids UAA1-4 were obtained with yields ranging from 5% to 44%. Experimental results demonstrated that [CuL2Cl]Cl exhibited superior photocatalytic efficiency compared to [CuL'2Cl]Cl, attributed to favourable electronic properties. In silico studies revealed strong binding strengths with E. faecalis DHFR (4M7U) for docked Schiff bases (SB) and unnatural α-amino acids (UAAs). In vitro studies further demonstrated significant antimicrobial and antifungal activity for SB2, SB3, and SB4, while none of the synthesized UAAs exhibited such properties, primarily due to the electronic and binding properties of these molecules.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4201-4214"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403030","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

Investigating the combined effect of copper, zinc, and iron ions on truncated and full-length Aβ peptides: insights from molecular dynamics simulation. 研究铜、锌和铁离子对截短和全长 Aβ 肽的综合影响：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 : 2025-05-01 Epub Date: 2024-01-08 DOI: 10.1080/07391102.2024.2301755

Mona Sohrabi, Mohammad Reza Bozorgmehr, Mohammad Momen-Heravi

{"title":"Investigating the combined effect of copper, zinc, and iron ions on truncated and full-length Aβ peptides: insights from molecular dynamics simulation.","authors":"Mona Sohrabi, Mohammad Reza Bozorgmehr, Mohammad Momen-Heravi","doi":"10.1080/07391102.2024.2301755","DOIUrl":"10.1080/07391102.2024.2301755","url":null,"abstract":"The truncated Aβ1 - 16 peptide containing the metal-binding domain is frequently used in in silico and experimental investigations because it is more soluble and thus more suitable for studies in solution and does not form amyloids. Several spectroscopic studies have shown that the metal binding of Aβ1 - 16 is very similar to that of the full-length Aβ1 - 42. However, since small changes can have a significant impact on aggregation, further experimental and theoretical are needed to elucidate the detailed structures of truncated and full-length Aβ. In this research, the binding of copper ion to the Aβ1 - 16 and Aβ1 - 42 has been studied by molecular dynamics simulation method. To investigate the effect of copper ion on beta-amyloid peptide structure, the simulations were repeated in the copper and zinc ions, copper and iron binary system, and the copper, zinc and iron ions ternary system. The conformation factor was calculated to calculate the binding affinity of copper ion to beta-amyloid peptide residues. The results showed that the initial 16 residues of the beta-amyloid peptide have high binding affinity for copper ions, and histidine 13 and histidine 14 have significantly higher binding affinity for copper ions in all studied systems. Zinc and iron ions were found to reduce the conformational factor of peptide residues in binding to copper ions, and the aggregation tendency was lower in the truncated structure. The SASA results suggest that the side chains of peptide residues are more affected by shortening and the presence of ions.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4165-4173"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377688","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

Deciphering insights into the binding mechanism and plasticity of Telacebec with M. tuberculosis cytochrome bcc-aa3 supercomplex through an unbiased molecular dynamics simulation, free-energy analysis, and DFT study. 通过无偏见分子动力学模拟、自由能分析和 DFT 研究，破解 Telacebec 与结核杆菌细胞色素 bcc-aa3 超级复合物的结合机制和可塑性。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2023-12-18 DOI: 10.1080/07391102.2023.2294833

Bedabrata Ray, Kuldeep K Roy

{"title":"Deciphering insights into the binding mechanism and plasticity of Telacebec with M. tuberculosis cytochrome bcc-aa3 supercomplex through an unbiased molecular dynamics simulation, free-energy analysis, and DFT study.","authors":"Bedabrata Ray, Kuldeep K Roy","doi":"10.1080/07391102.2023.2294833","DOIUrl":"10.1080/07391102.2023.2294833","url":null,"abstract":"The cytochrome bcc-aa3 supercomplex, a key component in the electron transport chain pathway involved in bacterial energy production and homeostasis, is a clinically validated target for tuberculosis (TB), leading to Telacebec (Q203). Telacebec is a potent candidate drug under Phase II clinical development for the treatment of drug-sensitive and drug-resistant TB. Recently, the cryo-electron microscopy structure of this supercomplex from Mycobacterium tuberculosis (Mtb) complexed with Q203 was resolved at 6.9 Å resolution (PDB ID: 7E1W). To understand the binding site (QP site) flexibility and Q203's stability at the QP site of the Mtb cytochrome bcc complex, we conducted molecular dynamics (MD) simulation and free energy analysis on this complex in an explicit hydrated lipid bilayer environment for 500 ns. Through this study, the persistence of a range of direct and indirect interactions was observed over the course of the simulation. The significance of the interactions with His375, Tyr161, Ala178, Ala179, Ile183, His355, Leu356, and Thr313 is underlined. Electrostatic energy was the primary source of the net binding free energy, regardless of the important interacting residues. The overall binding free energy for Q203 was -112.84 ± 7.73 kcal/mol, of which the electrostatic and lipophilic energy contributions were -116.31 ± 1.14 and -21.32 ± 2.35 kcal/mol, respectively. Meanwhile, DFT calculations were utilized to elucidate Q203's molecular properties. Overall, this study deciphers key insights into the cytochrome bcc-aa3 supercomplex with Q203 on the ground of molecular mechanics and quantum mechanics that may facilitate structure-based drug design and optimization for the discovery of the next-generation antitubercular drug(s).","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2968-2981"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803730","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 docking and MD simulations reveal protease inhibitors block the catalytic residues in Prp8 intein of Aspergillus fumigatus: a potential target for antimycotics. 分子对接和 MD 模拟揭示蛋白酶抑制剂可阻断烟曲霉 Prp8 内蛋白的催化残基：抗霉菌药物的潜在靶标。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2023-12-27 DOI: 10.1080/07391102.2023.2298735

Sunita Panda, Madhusmita Rout, Sarbani Mishra, Jyotirmayee Turuk, Sanghamitra Pati, Budheswar Dehury

{"title":"Molecular docking and MD simulations reveal protease inhibitors block the catalytic residues in Prp8 intein of Aspergillus fumigatus: a potential target for antimycotics.","authors":"Sunita Panda, Madhusmita Rout, Sarbani Mishra, Jyotirmayee Turuk, Sanghamitra Pati, Budheswar Dehury","doi":"10.1080/07391102.2023.2298735","DOIUrl":"10.1080/07391102.2023.2298735","url":null,"abstract":"Resistance to azoles and amphotericin B especially in Aspergillus fumigatus is a growing concern towards the treatment of invasive fungal infection. At this critical juncture, intein splicing would be a productive, and innovative target to establish therapies against resistant strains. Intein splicing is the central event for the activation of host protein, essential for the growth and survival of various microorganisms including A. fumigatus. The splicing process is a four-step protease-like nucleophilic cascade. Thus, we hypothesise that protease inhibitors would successfully halt intein splicing and potentially restrict the growth of the aforementioned pathogen. Using Rosetta Fold and molecular dynamics simulations, we modelled Prp8 intein structure; resembling classic intein fold with horse shoe shaped splicing domain. To fully comprehend the active site of Afu Prp8 intein, C1, T62, H65, H818, N819 from intein sequences and S820, the first C-extein residue are selected. Molecular docking shows that two FDA-approved drugs, i.e. Lufotrelvir and Remdesivir triphosphate efficiently interact with Prp8 intein from the assortment of 212 protease inhibitors. MD simulation portrayed that Prp8 undergoes conformational change upon ligand binding, and inferred the molecular recognition and stability of the docked complexes. Per-residue decomposition analysis confirms the importance of F: block R802, V803, and Q807 binding pocket in intein splicing domain towards recognition of inhibitors, along with active site residues through strong hydrogen bonds and hydrophobic contacts. However, in vitro and in vivo assays are required to confirm the inhibitory action on Prp8 intein splicing; which may pave the way for the development of new antifungals for A. fumigatus.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3526-3541"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040043","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

Natural sapogenins as potential inhibitors of aquaporins for targeted cancer therapy: computational insights into binding and inhibition mechanism. 天然苷元作为用于癌症靶向治疗的潜在水囊蛋白抑制剂：结合和抑制机制的计算见解。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2024-01-04 DOI: 10.1080/07391102.2023.2299743

Modhi O Alotaibi, Nahaa M Alotaibi, Maha Abdullah Alwaili, Nawaf Alshammari, Mohd Adnan, Mitesh Patel

{"title":"Natural sapogenins as potential inhibitors of aquaporins for targeted cancer therapy: computational insights into binding and inhibition mechanism.","authors":"Modhi O Alotaibi, Nahaa M Alotaibi, Maha Abdullah Alwaili, Nawaf Alshammari, Mohd Adnan, Mitesh Patel","doi":"10.1080/07391102.2023.2299743","DOIUrl":"10.1080/07391102.2023.2299743","url":null,"abstract":"Aquaporins (AQPs) are membrane proteins that facilitate the transport of water and other small molecules across biological membranes. AQPs are involved in various physiological processes and pathological conditions, including cancer, making them as potential targets for anticancer therapy. However, the development of selective and effective inhibitors of AQPs remains a challenge. In this study, we explored the possibility of using natural sapogenins, a class of plant-derived aglycones of saponins with diverse biological activities, as potential inhibitors of AQPs. We performed molecular docking, dynamics simulation and binding energy calculation to investigate the binding and inhibition mechanism of 19 sapogenins against 13 AQPs (AQP0-AQP13) that are overexpressed in various cancers. Our results showed that out of 19 sapogenins, 8 (Diosgenin, Gitogenin, Tigogenin, Ruscogenin, Yamogenin, Hecogenin, Sarsasapogenin and Smilagenin) exhibited acceptable drug-like characteristics. These sapogenin also exhibited favourable binding affinities in the range of -7.6 to -13.4 kcal/mol, and interactions within the AQP binding sites. Furthermore, MD simulations provided insights into stability and dynamics of the sapogenin-AQP complexes. Most of the fluctuations in binding pocket were observed for AQP0-Gitogenin and AQP4-Diosgenin. However, remaining protein-ligand complex showed stable root mean square deviation (RMSD) plots, strong hydrogen bonding interactions, stable solvent-accessible surface area (SASA) values and minimum distance to the receptor. These observations suggest that natural sapogenin hold promise as novel inhibitors of AQPs, offering a basis for the development of innovative therapeutic agents for cancer treatment. However, further validation of the identified compounds through experiments is essential for translating these findings into therapeutic applications.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3613-3634"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087021","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

High-throughput screening and in vitro evaluation of CSB-0914; a novel small molecule NF-κB inhibitor attenuating inflammatory responses through NF-κB, Nrf2 and HO-1 cross-talk. CSB-0914 的高通量筛选和体外评估；一种新型小分子 NF-κB 抑制剂，可通过 NF-κB、Nrf2 和 HO-1 的交叉作用减轻炎症反应。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2023-12-21 DOI: 10.1080/07391102.2023.2294377

Mesfer Al Shahrani, Mohammad AboHassan, Reem Gahtani, Mohammad Y Alshahrani, Muath Suliman, Irfan Ahmad, Mohd Saeed

{"title":"High-throughput screening and in vitro evaluation of CSB-0914; a novel small molecule NF-κB inhibitor attenuating inflammatory responses through NF-κB, Nrf2 and HO-1 cross-talk.","authors":"Mesfer Al Shahrani, Mohammad AboHassan, Reem Gahtani, Mohammad Y Alshahrani, Muath Suliman, Irfan Ahmad, Mohd Saeed","doi":"10.1080/07391102.2023.2294377","DOIUrl":"10.1080/07391102.2023.2294377","url":null,"abstract":"Unpleasant side effects of standard inflammatory drugs urges search for novel therapeutic candidates. This study aims in identifying novel anti-inflammatory NF-κB inhibitor by high-throughput computational and in-vitro pre-clinical approaches. Lead candidate selection was conducted by the use of computational docking molecular-dynamic simulations. The RBL-2H3 cell line, derived from rat basophils, was used to evaluate the release of cytokines and degranulation. The study focused on the study of neutrophil elastase and its role in cellular motility. Flow cytometry was utilized to evaluate the activation of basophils and the expression of critical signaling proteins. High throughput screening identified CSB-0914 to stably bind NF-κB-p50 subunit. Dose based loss in T NF-α and IL-2 release were observed in RBL-2H3 cells in addition to degranulation inhibition by CSB-0914. The compound demonstrated significant efficacy in reducing basophil activation assay induced by FcεRI receptors, with an IC50 value of 98.41 nM.. A dose dependent decrease in neutrophil migration and elastase were observed when treated with CSB- 0914. The compound was effective in decreasing. Upon stimulation, RBL-2H3 cells exhibited phosphorylation of NF-κB p-65 as well as upregulation of the Nrf2 and HO-1 signaling pathways. Collectively, our study has successfully identified a novel inhibitor called CSB-0914 that effectively regulates inflammatory responses. These reactions are primarily mediated by the interplay between NF-κB, Nrf2, and HO-1. The findings of this study provide support for the need to conduct more research on CSB-0914 with the aim of its development as a pharmaceutical agent for anti-inflammatory purposes.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2762-2771"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138829946","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 assisted investigation of phytochemicals as potential lead candidates against anti-apoptotic Bcl-B protein. 分子动力学模拟辅助研究植物化学物质作为抗凋亡 Bcl-B 蛋白的潜在先导候选物。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-01 Epub Date: 2023-12-18 DOI: 10.1080/07391102.2023.2295385

Rittik Bhati, Hazel Zadeng, Ekampreet Singh, Ankit Kumar, Monika Jain, J Senthil Kumaran, Amit Kumar Singh, Jayaraman Muthukumaran

{"title":"Molecular dynamics simulations assisted investigation of phytochemicals as potential lead candidates against anti-apoptotic Bcl-B protein.","authors":"Rittik Bhati, Hazel Zadeng, Ekampreet Singh, Ankit Kumar, Monika Jain, J Senthil Kumaran, Amit Kumar Singh, Jayaraman Muthukumaran","doi":"10.1080/07391102.2023.2295385","DOIUrl":"10.1080/07391102.2023.2295385","url":null,"abstract":"Due to the multifarious nature of cancer, finding a single definitive cure for this dreadful disease remains an elusive challenge. The dysregulation of the apoptotic pathway or programmed cell death, governed by the Bcl-2 family of proteins plays a crucial role in cancer development and progression. Bcl-B stands out as a unique anti-apoptotic protein from the Bcl-2 family that selectively binds to Bax which inhibits its pro-apoptotic function. Although several inhibitors are reported for Bcl-2 family proteins, no specific inhibitors are available against the anti-apoptotic Bcl-B protein. This study aims to address this research gap by using virtual screening of an in-house library of phytochemicals from seven anti-cancer medicinal plants to identify lead molecules against Bcl-B protein. Through pharmacokinetic analysis and molecular docking studies, we identified three lead candidates (Enterolactone, Piperine, and Protopine) based on appreciable drug-likeliness, ADME properties, and binding affinity values. The identified molecules also exhibited specific interactions with critical amino acid residues of the binding cleft, highlighting their potential as lead candidates. Finally, molecular dynamics simulations and MM/PBSA based binding free energy analysis revealed that Enterolactone (CID_114739) and Piperine (CID_638024) molecules were on par with Obatoclax (CID_11404337), which is a known inhibitor of the Bcl-2 family proteins.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3049-3063"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803815","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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