Journal of Biomolecular Structure & Dynamics最新文献_第5页

Insights into the crystal structure investigation and virtual screening approach of quinoxaline derivatives as potent against c-Jun N-terminal kinases 1. 喹喔啉衍生物对 c-Jun N 端激酶 1 的晶体结构研究和虚拟筛选方法的启示。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-01 Epub Date: 2024-02-07 DOI: 10.1080/07391102.2024.2305317

Shaaban K Mohamed, Subramani Karthikeyan, Omran A Omran, Atazaz Ahsin, Hanan Salah, Joel T Mague, Rashad Al-Salahi, Youness El Bakri

{"title":"Insights into the crystal structure investigation and virtual screening approach of quinoxaline derivatives as potent against c-Jun N-terminal kinases 1.","authors":"Shaaban K Mohamed, Subramani Karthikeyan, Omran A Omran, Atazaz Ahsin, Hanan Salah, Joel T Mague, Rashad Al-Salahi, Youness El Bakri","doi":"10.1080/07391102.2024.2305317","DOIUrl":"10.1080/07391102.2024.2305317","url":null,"abstract":"Quinoxaline derivatives are an important class of heterocyclic compounds in which N replaces one or more carbon atoms of the naphthalene ring and exhibit a wide spectrum of biological activities and therapeutic applications. As a result, we were encouraged to explore a new synthetic approach to quinoxaline derivatives. In this work, we synthesized two new derivatives namely, ethyl 4-(2-ethoxy-2-oxoethyl)-3-oxo-3,4-dihydroquinoxaline-2-carboxylate (2) and 3-oxo-3,4-dihydroquinoxaline-2-carbohydrazide (3) respectively. Their structures were confirmed by single-crystal X-ray analysis. Hirshfeld surface (HS) analysis is performed to understand the nature and magnitude of intermolecular interactions in the crystal packing. Density functional theory using the wb97xd/def2-TZVP method was chosen to explore their reactivity, electronic stability and optical properties. Charge transfer (CT) and orbital energies were analyzed via natural population analysis (NPA), and frontier molecular orbital (FMO) theory. The calculated excellent static hyperpolarizability (βo) indicates nonlinear optical (NLO) properties for 2 and 3. Both compounds show potent activity against c-Jun N-terminal kinases 1 (JNK 1) based on structural activity relationship studies, further subjected to molecular docking, molecular dynamics and ADMET analysis to understand their potential as drug candidates.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4784-4803"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697592","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

Switchable tetraplex elements in the heterogeneous nuclear ribonucleoprotein K promoter: micro-environment dictated structural transitions of G/C rich elements. 异质核糖核蛋白 K 启动子中的可转换四元组：微环境决定 G/C 富元的结构转换。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-01 Epub Date: 2024-01-18 DOI: 10.1080/07391102.2024.2303378

Debopriya Bose, Nilanjan Banerjee, Ananya Roy, Pallabi Sengupta, Subhrangsu Chatterjee

{"title":"Switchable tetraplex elements in the heterogeneous nuclear ribonucleoprotein K promoter: micro-environment dictated structural transitions of G/C rich elements.","authors":"Debopriya Bose, Nilanjan Banerjee, Ananya Roy, Pallabi Sengupta, Subhrangsu Chatterjee","doi":"10.1080/07391102.2024.2303378","DOIUrl":"10.1080/07391102.2024.2303378","url":null,"abstract":"We have elucidated the hnRNP K promoter as a hotspot for tetraplex-based molecular switches receptive to micro-environmental stimuli. We have characterised the structural features of four tetraplex-forming loci and identified them as binding sites of transcription factors. These segments form either G-quadruplex or i-motif structures, the structural dynamicity of which has been studied in depth via several biophysical techniques. The tetraplexes display high dynamicity and are influenced by both pH and KCl concentrations in vitro. The loci complementary to these sequences form additional non-canonical secondary structures. In the cellular context, the most eminent observation of this study is the binding of hnRNP K to the i-motif forming sequences in its own promoter. We are the first to report a probable transcriptional autoregulatory function of hnRNP K in coordination with higher-order DNA structures. Herein, we also report the positive interaction of the endogenous tetraplexes with Sp1, a well-known transcriptional regulator. Treatment with tetraplex-specific small molecule ligands further uncovered G-quadruplexes' functioning as repressors and i-motifs as activators in this context. Together, our findings strongly indicate the critical regulatory role of the identified tetraplex elements in the hnRNP K promoter.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4456-4473"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485642","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

Utilizing the drug repurposing strategy on current drugs: new leads for peptic ulcers via biochemical and biomolecular dynamics studies. 利用现有药物的药物再利用战略：通过生化和生物分子动力学研究开发治疗消化性溃疡的新线索。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-01 Epub Date: 2024-01-15 DOI: 10.1080/07391102.2024.2302926

Majid Khan, Arsalan Nizamani, Luqman Shah, Imran Ullah, Muhammad Waqas, Sobia Ahsan Halim, Farid Shokry Ataya, Ahmed M Elgazzar, Gaber El-Saber Batiha, Ajmal Khan, Ahmed Al-Harrasi

{"title":"Utilizing the drug repurposing strategy on current drugs: new leads for peptic ulcers via biochemical and biomolecular dynamics studies.","authors":"Majid Khan, Arsalan Nizamani, Luqman Shah, Imran Ullah, Muhammad Waqas, Sobia Ahsan Halim, Farid Shokry Ataya, Ahmed M Elgazzar, Gaber El-Saber Batiha, Ajmal Khan, Ahmed Al-Harrasi","doi":"10.1080/07391102.2024.2302926","DOIUrl":"10.1080/07391102.2024.2302926","url":null,"abstract":"The hyperactivity of urease enzymes plays a crucial role in the development of hepatic coma, hepatic encephalopathy, urolithiasis, gastric and peptic ulcers. Additionally, these enzymes adversely impact the soil's nitrogen efficiency for crop production. In the current study 100 known drugs were tested against Jack Bean urease and Proteus mirabilis urease and identified three inhibitors i.e. terbutaline (compound 1), Ketoprofen (compound 2) and norepinephrine bitartrate (compound 3). As a result, these compounds showed excellent inhibition against Jack Bean urease i.e. (IC50 = 2.1-11.3 µM), and Proteus mirabilis urease (4.8-11.9 µM). Moreover, in silico studies demonstrate maximum interactions of compounds in the enzyme's active site. Furthermore, intermolecular interactions between compounds and enzyme atoms were examined using STD-NMR spectrophotometry. In parallel, molecular dynamics simulation was carried out to study compounds dynamic behavior within the urease binding region. Urease remained stable during most of the simulation time and ligands were bound in the protein active pocket as observed from the Root mean square deviation (RMSD) and ligand RMSD analyses. Furthermore, these compounds display interactions with the crucial residues, including His492 and Asp633, in 100 ns simulations. In the binding energy analysis, norepinephrine bitartrate exhibited the highest binding energy (-76.32 kcal/mol) followed by Ketoprofen (-65.56 kcal/mol) and terbutaline (-62.15 kcal/mol), as compared to acetohydroxamic acid (-52.86 kcal/mol). The current findings highlight the potential of drug repurposing as an effective approach for identifying novel anti-urease compounds.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4341-4354"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472476","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

Bioactive metabolites of licorice and thyme as potential inhibitors of Cox1 enzyme of phytopathogens of Capsicum annuum L.: In-silico approaches. 甘草和百里香的生物活性代谢物作为辣椒植株病原体 Cox1 酶的潜在抑制剂：硅方法。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-01 Epub Date: 2024-01-12 DOI: 10.1080/07391102.2024.2303603

Himanshu Arora, Gourav Choudhir, Arunava Sengupta, Abhishek Sharma, Satyawati Sharma

{"title":"Bioactive metabolites of licorice and thyme as potential inhibitors of Cox1 enzyme of phytopathogens of Capsicum annuum L.: In-silico approaches.","authors":"Himanshu Arora, Gourav Choudhir, Arunava Sengupta, Abhishek Sharma, Satyawati Sharma","doi":"10.1080/07391102.2024.2303603","DOIUrl":"10.1080/07391102.2024.2303603","url":null,"abstract":"Cytochrome c oxidase subunit 1 (Cox1), a key enzyme, has a crucial role in cellular respiration in eukaryotes and prokaryotes. Generally, respiratory inhibitors are considered one of the types of chemical pesticides. Thyme oil and licorice aqueous extract have been reported to have antifungal activities against fungal phytopathogens of Capsicum annuum L., i.e., Colletotrichum capsici, Fusarium oxysporum, and Pythium aphanidermatum. The present study focuses on identifying the key bioactive molecules of thyme and licorice botanicals inhibiting the activity of the Cox1 enzymes of the above mentioned phytopathogens, employing the in-silico approach. From a wide range of bioactive molecules screened, the molecular docking indicated trans-carveol, carvacrol, kaempferol 3-rhamnoside 7-xyloside, kaempferitrin, and astragalin 7-rhamnoside as the potential inhibitors for Cox1 of C. capsici, β-Caryophyllene, Caryophyllene acetate, hispaglabridin A, kaempferol 3-rhamnoside 7-xyloside and licorice glycoside A for Cox1 of F. oxysporum and (+)-Longifolen, Caryophyllene acetate, Hispaglabridin A, Neoliquiritin 2''-apioside and Licorice-saponin A3 for Cox1 of P. aphanidermatum. Most of the top-scoring bioactive molecules exhibited higher binding affinity with the targets than the chemical compound, i.e., carbendazim. Density functional theory (DFT) analysis confirmed the reactivity of the top-docked compounds. Molecular dynamic simulations confirmed the stability of docked complexes when evaluated through multiple descriptors. Additionally, MM/PBSA analysis supported the findings, indicating the spontaneous binding of the enzymes to the screened ligands. ADMET analysis revealed the safety of the selected bioactive compounds. The present findings could be useful in developing biopesticidal formulations as efficient and sustainable alternatives to chemical pesticides.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4534-4551"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466481","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 Campylobacter jejuni DsbA1 protein dynamics in the presence of anti-virulent compounds: a multi-pronged computer-aided approach. 解密空肠弯曲杆菌 DsbA1 蛋白在抗病毒化合物作用下的动态变化：一种多管齐下的计算机辅助方法。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-01 Epub Date: 2024-01-17 DOI: 10.1080/07391102.2024.2302945

Mashael A Alghamdi, Faizul Azam, Prawez Alam

{"title":"Deciphering Campylobacter jejuni DsbA1 protein dynamics in the presence of anti-virulent compounds: a multi-pronged computer-aided approach.","authors":"Mashael A Alghamdi, Faizul Azam, Prawez Alam","doi":"10.1080/07391102.2024.2302945","DOIUrl":"10.1080/07391102.2024.2302945","url":null,"abstract":"The current study aims to evaluate Asinex library compounds against Campylobacter jejuni DsbA1 protein, a thiol disulfide oxidoreductase enzyme that plays a major role in the oxidative folding of bacterial virulence proteins, making it a promising anti-viral drug target. By employing several techniques of computer-aided drug design, BDC25697459, BDD33601083, and BDC30129064 were identified with binding energy scores of -8.8 kcal/mol, -8.8 kcal/mol, and -8.3 kcal/mol, respectively. However, the control molecule, tetraethylene glycol, exhibited a binding energy score of -7.0 kcal/mol. The control, BDD33601083, and BDC30129064 were unveiled to bind the same co-crystallized binding site (pocket 1), while BDC25697459 interacted with a new binding pocket (pocket 2) adjacent to the control binding region. The molecular dynamics simulation showed that complexes exhibit stable dynamics without significant global or residue-level fluctuations. The average RMSD values were in the range of 2.07 Å-2.45 Å. Similarly, mean RMSF was recorded between 1.30 and 1.42 Å. The C. jejuni DsbA1 was also observed as compact in the presence of the compounds, showing a mean RoG value in the range of 16.42 Å-16.55 Å. In terms of MM/PBSA binding energy, the BDC30129064 complex was ranked top with -44.88 ± 4.14 kcal/mol, whereas the positive control molecule exhibited -22.22 ± 3.33 kcal/mol. From a pharmacokinetic perspective, the compounds are suitable candidates for clinical trial investigation. Preliminary computational analysis of these virtual hits indicates that these compounds have a low potential for ADME and toxicity-associated liabilities. In summary, the compounds displayed a high affinity for the C. jejuni DsbA1 protein, indicating potential efficacy that requires further investigation.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4388-4404"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478602","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

MehNet: a vigesimal-based model by amino acid melting points generates unique ID numbers for protein sequences. MehNet：通过氨基酸熔点生成蛋白质序列唯一 ID 号的基于 vigesimal 的模型。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-01 Epub Date: 2024-01-17 DOI: 10.1080/07391102.2024.2302937

Mehmet Erten

{"title":"MehNet: a vigesimal-based model by amino acid melting points generates unique ID numbers for protein sequences.","authors":"Mehmet Erten","doi":"10.1080/07391102.2024.2302937","DOIUrl":"10.1080/07391102.2024.2302937","url":null,"abstract":"The amino acid encoding plays a pivotal role in machine learning-based methods for predicting protein structure and function, as well as in protein mapping techniques. Additionally, the classification of protein sequences presents its own challenges. The current study aims to assign a constant value to each amino acid, thereby creating distinctions among protein sequences. The datasets used in this study were obtained from the UniProt Knowledgebase. Subsequently, these datasets underwent preprocessing steps, and identical sequences were categorized under the same headings. Each amino acid was ranked based on its respective melting point and was assigned a vigesimal digit. These generated vigesimal digits were subsequently converted to decimal values. The centerpiece of this methodology was the melting point hashing table, which was given the name 'MehNet'. Ultimately, each protein sequence was assigned a unique identification number. This approach successfully digitized protein sequences. Notably, experiments involving randomly distributed vigesimal digits for amino acids did not yield results as promising as those achieved with MehNet. The model's classification phase, which utilizes a k-nearest neighbors (kNN) classifier, demonstrates exceptional performance in miscellaneous viral sequences. It achieves high accuracy rates, with an overall accuracy of 99.75%. Notably, it achieves an outstanding accuracy of 99.92% for the Influenza C class, highlighting its ability to distinguish closely related viral sequences.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4355-4361"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478607","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

Application of temperature-dependent and steered molecular dynamics simulation to screen anti-dengue compounds against Marburg virus. 应用温度依赖性和定向分子动力学模拟筛选针对马尔堡病毒的抗登革热化合物。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-01 Epub Date: 2024-01-17 DOI: 10.1080/07391102.2024.2303386

Ali A Rabaan, Zainab H Almansour, Ali Al Bshabshe, Muhammad A Halwani, Maha F Al-Subaie, Nawal A Al Kaabi, Saleh A Alshamrani, Ahmad A Alshehri, Mohammed H Nahari, Ali S Alqahtani, Mashael Alhajri, Mohammed Alissa

{"title":"Application of temperature-dependent and steered molecular dynamics simulation to screen anti-dengue compounds against Marburg virus.","authors":"Ali A Rabaan, Zainab H Almansour, Ali Al Bshabshe, Muhammad A Halwani, Maha F Al-Subaie, Nawal A Al Kaabi, Saleh A Alshamrani, Ahmad A Alshehri, Mohammed H Nahari, Ali S Alqahtani, Mashael Alhajri, Mohammed Alissa","doi":"10.1080/07391102.2024.2303386","DOIUrl":"10.1080/07391102.2024.2303386","url":null,"abstract":"Marburg virus infections are extremely fatal with a fatality range of 23% to 90%, therefore there is an urgent requirement to design and develop efficient therapeutic molecules. Here, a comprehensive temperature-dependent molecular dynamics (MD) simulation method was implemented to identify the potential molecule from the anti-dengue compound library that can inhibit the function of the VP24 protein of Marburg. Virtual high throughput screening identified five effective binders of VP24 after screening 484 anti-dengue compounds. These compounds were treated in MD simulation at four different temperatures: 300, 340, 380, and 420 K. Higher temperatures showed dissociation of hit compounds from the protein. Further, triplicates of 100 ns MD simulation were conducted which showed that compounds ID = 118717693, and ID = 5361 showed strong stability with the protein molecule. These compounds were further validated using <math><mo>Δ</mo><mi>G</mi></math> binding free energies and they showed: -30.38 kcal/mol, and -67.83 kcal/mol binding free energies, respectively. Later, these two compounds were used in steered MD simulation to detect its dissociation. Compound ID = 5361 showed the maximum pulling force of 199.02 kcal/mol/nm to dissociate the protein-ligand complex while ID = 118717693 had a pulling force of 101.11 kcal/mol/nm, respectively. This ligand highest number of hydrogen bonds with varying occupancies at 89.93%, 69.80%, 57.93%, 52.33%, and 50.63%. This study showed that ID = 5361 can bind with the VP24 strongly and has the potential to inhibit its function which can be validated in the in-vitro experiment.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4474-4493"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485599","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

Developing of SARS-CoV-2 fusion protein expressed in E. coli Shuffle T7 for enhanced ELISA detection sensitivity - an integrated experimental and bioinformatic approach. 开发在大肠杆菌 Shuffle T7 中表达的 SARS-CoV-2 融合蛋白以提高 ELISA 检测灵敏度--一种综合实验和生物信息学方法。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-01 Epub Date: 2024-01-17 DOI: 10.1080/07391102.2024.2302941

Sohrab Sam, Hamideh Ofoghi, Behrokh Farahmand

{"title":"Developing of SARS-CoV-2 fusion protein expressed in E. coli Shuffle T7 for enhanced ELISA detection sensitivity - an integrated experimental and bioinformatic approach.","authors":"Sohrab Sam, Hamideh Ofoghi, Behrokh Farahmand","doi":"10.1080/07391102.2024.2302941","DOIUrl":"10.1080/07391102.2024.2302941","url":null,"abstract":"In the recent COVID-19 pandemic, developing effective diagnostic assays is crucial for controlling the spread of the SARS-CoV-2 virus. Multi-domain fusion proteins are a promising approach to detecting SARS-CoV-2 antibodies. In this study, we designed an antigen named CoV2-Pro, containing two RBD domains from SARS-CoV-2 Omicron and Delta variants and one CTD domain of the nucleoprotein in the order of RBD-RBD-N, linked by a super flexible glycine linker. We evaluated the suitability of E. coli Shuffle T7 and BL21 (DE3) strain for expressing CoV2-Pro. Moreover, Bioinformatic studies were conducted first to analyze the tertiary structure of CoV2-Pro. The CoV2-Pro sequences were cloned into a pET-32b (+) vector for expression in E. coli Shuffle T7 and BL21 (DE3). SDS-PAGE and western blot confirmed the protein expression and folding structure. The CoV2-Pro-TRX was purified by Ni-NTA affinity chromatography. Dot blot analysis was performed to evaluate the antigenic characterization of the CoV2-Pro. A molecular docking simulation was conducted to assess the binding affinity of CoV2-Pro with LY-COV555 (Bamlanivimab) monoclonal antibody. A molecular dynamic was performed to analyze the stability of the structure. Bioinformatic and experimental studies revealed a stable conformational 3D structure of the CoV2-Pro. The CoV2-Pro interacted with SARS-CoV-2 antibodies, confirming the correct antigenic structure. We assert with confidence that CoV2-Pro is ideal for developing an ELISA assay for precise diagnosis and rigorous vaccine evaluation during the COVID-19 prevalence.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4440-4455"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485602","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

Insightful t-SNE guided exploration spotlighting Palbociclib and Ribociclib analogues as novel WEE1 kinase inhibitory candidates. 富有洞察力的 t-SNE 引导探索发现 Palbociclib 和 Ribociclib 类似物是新型 WEE1 激酶抑制候选物。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-01 Epub Date: 2024-01-18 DOI: 10.1080/07391102.2024.2305316

Rajesh Muthuraj, Dhanushya Gopal, Iqrar Ahmed, Jaikanth Chandrasekaran

{"title":"Insightful t-SNE guided exploration spotlighting Palbociclib and Ribociclib analogues as novel WEE1 kinase inhibitory candidates.","authors":"Rajesh Muthuraj, Dhanushya Gopal, Iqrar Ahmed, Jaikanth Chandrasekaran","doi":"10.1080/07391102.2024.2305316","DOIUrl":"10.1080/07391102.2024.2305316","url":null,"abstract":"In the era of targeted therapeutics, protein kinases like WEE1 have become pivotal drug targets, especially for cancer therapy. Utilizing a multi-faceted approach, our study adds fresh insights to this endeavour. We employed the t-SNE algorithm, combined with ECFP4 fingerprints, to analyse the molecular similarity between FDA-approved drugs and known clinical trial inhibitors. Our t-SNE analysis identified the closest clusters to known inhibitors and selected 11 FDA-approved drugs for further study. Using the DrugSpaceX platform, we generated analogues for these 11 FDA-approved drugs. These analogues were refined according to Lipinski's Rule of Five and Synthetic Accessibility scores, yielding 68,640 analogues for additional scrutiny. Among these, derivatives of Palbociclib and Ribociclib stood out as the most promising WEE1 inhibitors, based on docking scores and interaction patterns. Molecular dynamics simulations validated the stability of these protein-ligand interactions, particularly for DE50607359, a top-ranked Palbociclib analogue, which also met most pharmacokinetic parameters within acceptable limits. Our study uncovers new candidates for WEE1 inhibition not previously reported. With our multi-layered computational strategy, we provide a solid foundation for future experimental validation and targeted drug development in cancer therapeutics.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4716-4728"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491499","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 ZINC08101049 as a potential IL1β inhibitor through molecular docking and MD simulations for cancer therapeutics. 通过用于癌症治疗的分子对接和 MD 模拟，确定 ZINC08101049 为一种潜在的 IL1β 抑制剂。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-06-01 Epub Date: 2024-01-19 DOI: 10.1080/07391102.2024.2304669

Mohammad Y Alshahrani, Muath Suliman, Mohammad Ali Abdullah Almoyad, Shadma Wahab

{"title":"Identification of ZINC08101049 as a potential IL1β inhibitor through molecular docking and MD simulations for cancer therapeutics.","authors":"Mohammad Y Alshahrani, Muath Suliman, Mohammad Ali Abdullah Almoyad, Shadma Wahab","doi":"10.1080/07391102.2024.2304669","DOIUrl":"10.1080/07391102.2024.2304669","url":null,"abstract":"Cancer is a significant global health concern that has a major impact on morbidity and mortality worldwide. Research has demonstrated the involvement of Interleukin-1 beta (IL1β) in various aspects of cancer development and progression, including angiogenesis, tumor growth and metastasis. Consequently, targeting IL1β activity represents a promising approach for cancer therapeutics. In this study, we utilized molecular docking and MD simulations to discover potent IL1β inhibitors for the treatment of cancer. Five thousand compounds from ZINC15 database were screened against IL1β target, and the top ten small molecules were selected based on their binding energy. The small molecule named 'ZINC08101049' was prioritized based on binding energy (-9.1 kcal/Mol) and residual interaction specifically forming seven hydrogen bonds with amino acid residues namely GLN81, GLY136, LEU134, LYS138, SER84, THR137 and TYR24 of IL1β. Next, IL1β alone and in complex with ZINC08101049 was subjected to MD simulations to determine their behavior at atomic level. The results of molecular docking and MD simulation revealed ZINC08101049 as a potential inhibitor of IL1β, reflecting that ZINC08101049 can emerge as a promising small molecule paving for cancer therapeutics.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4603-4614"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491483","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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