Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Identification of novel inhibitors of cancer target telomerase using a dual structure-based pharmacophore approach to virtually screen libraries, molecular docking and validation by molecular dynamics simulations.","authors":"Divpreet Kaur, Daman Saluja, Madhu Chopra","doi":"10.1080/07391102.2024.2443130","DOIUrl":"https://doi.org/10.1080/07391102.2024.2443130","url":null,"abstract":"<p><p>In about 85% of cancer malignancies, replicative immortality caused by increased telomerase activity makes it an attractive target for developing anticancer therapeutics. However, the lack of approved small-molecule inhibitors rooted in the structural ambiguity of telomerase has impeded drug development for decades. In this study, we have exploited the FVYL pocket in the thumb domain, which plays a key role in the enzyme's processivity. Due to the unavailability of a co-crystalized structure of BIBR1532 with the catalytic hTERT thumb domain, we utilized the molecular dynamics method to identify the precise binding site of the inhibitor. Two pharmacophore models were generated and validated for the putative (Site-I) and newly identified (Site-II) binding pockets which were screened virtually through the ChemDiv anticancer library, Otava drug-like green collection to identify novel lead compounds, and Binding database to screen out thumb domain-specific telomerase inhibitors. The top hits obtained were filtered using drug-likeliness parameters followed by redocking using a three-level screening strategy into their binding site. The structural investigation, molecular docking studies, and confirmatory molecular dynamics revealed that the exact binding site of BIBR1532 is away from the reported FVYL pocket with characteristic interactions conserved. Subsequently, the lead compounds with the highest docking scores and significant interactions in the newly discovered extended FVYL pocket were validated using 100 ns MD simulations. Additionally, cross-validated binding free energy calculations were performed using MM-PB(GB)SA methods followed by PCA and FEL characterization. The identified top lead compounds can be validated <i>in vitro</i> and taken forward for anticancer drug development.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-24"},"PeriodicalIF":2.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binding kinetics of highly mutated HIV-1 subtype C protease inhibition by Lopinavir and Darunavir in the face of altered conformational dynamics.","authors":"Simeon Eche, Ajit Kumar, Nelson Sonela, Michelle L Gordon","doi":"10.1080/07391102.2024.2426078","DOIUrl":"https://doi.org/10.1080/07391102.2024.2426078","url":null,"abstract":"<p><p>Highly mutated HIV-1 protease (PR) compromises the efficacy of lopinavir (LPV) and darunavir (DRV) used to formulate salvage regimens in HIV/AIDS management. Here, we report the kinetics of inhibition of lopinavir (LPV) and darunavir (DRV) on highly mutated South African HIV-1 subtype C PR obtained from clinical isolates. The wild-type and mutant South African HIV-1 subtype C PR were cloned and purified. Enzyme inhibition assays and fluorescence spectroscopy were utilized to determine the binding kinetics of LPV and DRV with the wild-type and mutant HIV-1 PR variants. Like DRV, the results of this study show that LPV has a mixed-type inhibition mechanism, which indicates the possibility of a second binding site on HIV-1 PR. Both LPV and DRV poorly inhibited the highly mutated HIV-1 PR variants and had a markedly increased dissociation rate cons bound to the mutant variants compared to the wild type. The fast dissociation of these inhibitors translated into a short residence time of the inhibitor bound to the mutant HIV-1 PR variants. Fluorescent spectroscopy showed that the changes in the tertiary structure of the mutant HIV-1 PR variants were associated with a more open conformation. This open conformation was associated with altered conformational dynamics, which may have resulted in the loss of tight binding of LPV and DRV. This study's findings provide insight into the mechanism of resistance to LPV and DRV by highly mutated HIV-1 PR and provide information supporting the use of binding kinetics measurement in understanding HIV-1 PR inhibitor drug resistance evolution.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing therapeutic targets and drugs from Chinese medicine for ulcerative colitis using bioinformatics.","authors":"Feng Xu, Xiaofen Li, Xiangpei Wang, Hongmei Wu, Song Chen, Jianyang Chen, Xiangxi Kong, Zhenglin Yang","doi":"10.1080/07391102.2024.2440651","DOIUrl":"https://doi.org/10.1080/07391102.2024.2440651","url":null,"abstract":"<p><p>Pathogenesis and therapeutic drugs for ulcerative colitis (UC) have plagued researchers worldwide. In this study, therapeutic targets, and drugs from Chinese medicines for UC were screened using bioinformatics. We downloaded five datasets from the GEO database and three machine learning algorithms were used for screening diagnostic biomarkers of UC. Combined with the differential genes for UC, gene sets related to bile acid metabolism, short-chain fatty acids, apoptosis, pyroptosis, G-protein-coupled receptors, mitochondria, and autophagy were collected to screen the core targets, and analyze the association of therapeutic genes (diagnostic biomarkers and core targets) with immune cells. In addition, screening ingredients of Chinese medicines based on UC therapeutic targets was performed. Molecular docking, molecular dynamics simulation, and literature validation were also performed. The screening yielded 37 key therapeutic targets, including 5 diagnostic biomarkers (CCL11, CXCL1, PDZK1IP1, TIMP1, and UGT2A3) and 32 core targets based on hot gene sets. Immune cell infiltration was strongly associated with therapeutic targets in UC, especially neutrophils, macrophages, mast cells, and dendritic cells. Furthermore, a total of 33 compounds with high safety had been recognized as having potential to mitigate UC by reverse prediction from Chinese medicines, and molecular docking, molecular dynamics simulation, and literature reports preliminarily validated the screening results. Although further experimental validation is needed, this work provides some potential therapeutic targets and drugs from Chinese medicines against UC.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-11"},"PeriodicalIF":2.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA protection, molecular docking, molecular dynamic, enzyme inhibition, and kinetics studies of apigenin isolated from <i>Nepeta baytopii</i> Hedge & Lamond by bioactivity-guided fractionation.","authors":"Semiha Yenigun, Yunus Basar, Yasar Ipek, Lutfi Behcet, Ibrahim Demirtas, Tevfik Ozen","doi":"10.1080/07391102.2024.2442753","DOIUrl":"https://doi.org/10.1080/07391102.2024.2442753","url":null,"abstract":"<p><p>Plant-derived bioactive substances have demonstrated significant qualities that suggest they may be crucial in preventing various chronic diseases. Flavonoids, which include apigenin, are the biggest group of polyphenols. In our study, we aimed to obtain the methanol-chloroform (1:1) extract from the aerial parts of <i>Nepeta baytopii</i> Hedge & Lamond and purify the apigenin using bioactivity-guided isolation to separate the active fraction. The current <i>in vitro</i> study provides updated knowledge on apigenin regarding its previously unresearched DNA protection activity and enzyme inhibition, enzyme inhibition kinetics, and enzyme-apigenin interactions. In this context, these studies will be the first and will contribute to the literature. Apigenin had high urease (IC₅₀-5.00 ± 0.00 µM), butyrlcholinesterase (BChE:IC₅₀-10.48 ± 0.00 µM), and tyrosinase (IC₅₀-177.82 ± 14.40 µM) inhibition activities, while inhibition binding constants were high in urease (K<i>_i</i>-0.05 mM), tyrosinase (K<i>_i</i>-0.06 mM), and carbonic anhydrase (K<i>_i</i>-0.08 mM). The binding affinities and constants of the interaction were also ascertained to be high for BChE (-9.50 kcal/mol, and K<i>_i</i>-0.11 µM), and tyrosinase (-8.80 kcal/mol, and K<i>_i</i>, 0.62 µM) with apigenin. In summary, apigenin can be used as an inhibitor for five enzymes. These results will give priority to further studies. Apigenin showed high DNA protection activity with a Form I value of 67.37%. These data demonstrated that the interaction formed by BChE-apigenin gave the best results regarding enzyme inhibition and enzyme-molecule interaction. The stability of this complex was evaluated using molecular dynamics modeling.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trailblazing real-world-data to confront hepatocellular carcinoma - disinterring repurposable drugs by amalgamating avant-garde stratagems.","authors":"Gouri Nair, Ganesan Rajalekshmi Saraswathy, Prasanna Kumar Reddy Gayam, Jesil Mathew Aranjani, T P Krishna Murthy, Viswam Subeesh","doi":"10.1080/07391102.2024.2438361","DOIUrl":"https://doi.org/10.1080/07391102.2024.2438361","url":null,"abstract":"<p><p>Drug repurposing is preferred over de-novo drug discovery to unveil the therapeutic applications of existing drug candidates before investing considerable resources in unexplored novel chemical entities. This study demonstrated multifaceted stratagems to reconnoiter promising repurposable candidates against Hepatocellular Carcinoma (HCC) by amalgamating Real-World-Data (RWD) with bioinformatics algorithms corroborated with <i>in-silico</i> and <i>in-vitro</i> studies. At the outset, the RWD from the Food and Drug Administration Adverse Event Reporting System (FAERS) was explored to navigate signals to retrieve repurposable drugs that are inversely associated with HCC via Disproportionality Analysis. Further, transcriptomic analysis was used to capture the potential targets of HCC. Following this, the interactions between repurposable drugs and HCC targets were virtually demonstrated via molecular docking and Molecular Dynamics Simulations (MDS). Furthermore, additional cytotoxicity and gene expression experiments were conducted to corroborate the results. Overall, 64 drugs with Drug Event >5 were shortlisted as prospective repurposable drugs as per the RWD obtained from FAERS. The transcriptomic analysis highlighted significant upregulation of Cyclin A2 (CCNA2) in HCC, which activates Cyclin Dependent Kinase 2 (CDK2). Further, <i>in-silico</i> studies identified Losartan and Allopurinol, with docking scores of -7.11 and -6.219, respectively, as potential repurposable drugs. The selected drugs underwent further scrutiny through in-vitro studies. The treatment of HepG2 cells with Allopurinol resulted in significant downregulation of CCNA2/CDK2 expression with an elevation in reactive oxygen species levels, uncovering Allopurinol's anticancer mechanism through cellular apoptosis. This study suggests the importance of RWD in drug repurposing and the potential of Allopurinol as a repurposable drug against HCC.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational design and validation of small molecule inhibitors for type III phosphatidylinositol-4-kinase alpha, a hepatitis C drug target.","authors":"Jishu Pagag, Priyanka Andola, Laxman Durgam, Lalitha Guruprasad","doi":"10.1080/07391102.2024.2440645","DOIUrl":"https://doi.org/10.1080/07391102.2024.2440645","url":null,"abstract":"<p><p>According to World Health Organization reports of the year 2022, nearly 242,000 people died from hepatitis C that causes liver cirrhosis and hepatocellular carcinoma. Phosphatidylinositol-4-kinase type III alpha (PI4KIIIα), a lipid kinase interacts with the hepatitis C virus non-structural 5 A protein (NS5A) to produce phosphoinositol-4-phosphate (PI4P), which enriches the hepatitis C virus replication complex. Patients with hepatitis C virus infection in the liver have been associated with increased levels of PI4P at the endoplasmic reticulum. To initiate viral replication, the hepatitis C virus must assemble numerous host cellular proteins into distinct membrane replication structures. A crucial element of these replication organelles is PI4KIIIα. Therefore, inhibition of PI4KIIIα is one of the most needed therapeutic approaches for the treatment of the disease. In this direction, a combination of pharmacophore-based virtual screening, molecular docking, molecular dynamics (MD) simulations were studied for PI4KIIIα. The stability of the complexes throughout MD simulations was evaluated from their binding free energies, post-MD analysis, and further the drug-like properties of the selected molecules were analyzed. Six molecules were finally selected as the likely hit molecules based on binding free energies, normal mode analysis, and their drug-like properties. The findings of this work suggest that the selected small molecules may be used as lead molecules for the development of novel PI4KIIIα inhibitors. It is also anticipated that these thorough studies will be helpful in the structure-based drug design of PI4KIIIα inhibitors.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced targeting efficacy of baicalein analogues on the dimeric state of SARS-CoV-2 3CL protease compared to monomeric state.","authors":"Ahmed I Foudah, Aftab Alam","doi":"10.1080/07391102.2024.2437522","DOIUrl":"https://doi.org/10.1080/07391102.2024.2437522","url":null,"abstract":"<p><p>The COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2, has been a global threat affecting the entire world. It is a single-stranded RNA virus that belongs to the coronavirus family. In SARS-CoV2, the 3CL protease protein significantly contributes to viral replication and is responsible for viral polyprotein cleavage. These factors make 3CL protease a promising drug target to inhibit the growth of SARS-CoV-2. In this study, using in silico approaches, we have targeted the 3CL protease of SARS-CoV-2 to identify promising antiviral candidates for COVID-19 treatment. Here, 463 structural analogs of Baicalein compounds were collected initially, and by employing the quantitative structure-activity relationship (QSAR) technique on 76 antiviral compounds, screening was done against monomeric and dimeric versions of the target protein. Further, based on the molecular interaction studies and MD simulation, followed by validation of the obtained simulation trajectories using PCA and MM/PBSA calculation, it was observed that ligands showed better binding stability with dimeric proteins than monomeric proteins and can be used as suitable therapeutic candidates for SARS-CoV2 treatment. The MD simulation showed a favorable, robust outcome for the 46885476 when bound to the dimeric state. It matched the control in the number of hydrogen bonds and conformational stability. This molecule also directly impacted the catalytic dyads of the protein, suggesting potential inhibitory action. In addition, this study helps to accelerate the drug development process against SARS-CoV2 through the observed <i>in-silico</i> results, which need to be validated using clinical experiments in future studies.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential oil constituents of regional ethnomedicinal plants as potential inhibitors of SARS-CoV-2 M^pro: an integrated molecular docking, molecular dynamics and QM/MM study.","authors":"Ambalika Phonglo, Dikshita Dowerah, Srutishree Sarma, Najima Ahmed, Priyanka Dutta, Moumita Basumutary, Ramesh Ch Deka","doi":"10.1080/07391102.2024.2440148","DOIUrl":"https://doi.org/10.1080/07391102.2024.2440148","url":null,"abstract":"<p><p>The scientific community has achieved a remarkable milestone by creating efficacious vaccines against the SARS-CoV-2 virus. The treatment alternatives are still restricted, though. The bioactive ingredients present in natural plants are known to exhibit diverse pharmacological effects against many diseases. Using computational techniques such as molecular docking, drug-likeness, ADMET study, MD simulation, and our own N-layered Integrated molecular Orbital and Molecular mechanics (ONIOM) calculations, this study aimed to investigate essential oil constituents of <i>Lindera neesiana</i>, <i>Litsea cubeba</i> and <i>Zanthoxylum armatum DC</i> plants as a potential natural inhibitor of SARS-CoV-2 main protease (M^pro). To determine their binding affinity, 107 phytochemical substances in total were docked inside the binding pocket of M^pro. Copaene showed the highest binding affinity among the 107 compounds, with an energy of -7.90 kcal/mol. Furthermore, physiochemical and ADMET properties were evaluated for the top five phytocompounds. The studied phytocompounds showed good physiochemical and pharmacokinetic behaviour with no associated toxicity. MD simulation further provided evidence for stable interaction of phytocompounds within the binding pocket of M^pro. Subsequently, ONIOM calculation was done on the best-hit complex, wherein the hydrogen bonding interactions were retained with appreciable negative energy. These <i>in silico</i> results indicate that the specific phytocompounds present in essential oils of <i>L. neesiana, L. cubeba,</i> and <i>Z. armatum DC</i> have significant inhibitor ability against SARS-CoV-2 main protease and could be explored for future therapeutic investigations.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-23"},"PeriodicalIF":2.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicity of anthraquinone derivatives in relation to non-linear optical properties and electron correlation.","authors":"Puja O Gupta, Praful S Patil, Nagaiyan Sekar","doi":"10.1080/07391102.2024.2439582","DOIUrl":"https://doi.org/10.1080/07391102.2024.2439582","url":null,"abstract":"<p><p>1,4-Dialkylamino -5,8-dihydroxy anthraquinones are investigated using density functional theory (DFT) and time-dependent DFT (TD-DFT) for their growth inhibitory potential. The frontier molecular orbital shows that the electron density is located at the anthraquinone core and at the substituents NH and OH in both HOMO as well as in LUMO. The chemical potential and electrophilicity index showed a direct relation, while hardness and hyperhardness had an inverse association with an energy gap. The results of the molecular docking analysis revealed that the anthraquinone molecules have a high affinity for the primary targets of the DNA topoisomerase IIα enzyme. The docking results showed good binding ability with extremely energetically stable scores ranging from -8.9 to -7.6 kcal/mol. Electron correlation descriptors showed a direct link with NLO properties and toxicity.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico design, modelling and molecular mechanisms of Axl receptor tyrosine kinase inhibitors.","authors":"Gatta K R S Naresh, Lalitha Guruprasad","doi":"10.1080/07391102.2024.2439578","DOIUrl":"https://doi.org/10.1080/07391102.2024.2439578","url":null,"abstract":"<p><p>A kinase domain from receptor tyrosine kinases (RTKs) regulate intracellular communications to control cellular metabolic activities. Some of the malignant cells have upregulated and overexpressed RTKs which are responsible for angiogenesis in many metastatic cancers. Axl RTK is present in most of the eukaryotic cells and all metastatic cancer cells have overexpressed Axl tyrosine kinase to trigger uncontrolled growth and angiogenesis in the malignant cells. The upregulated kinases can be inhibited in its active and inactive states in the presence of small organic molecule inhibitors. Kinase inhibitors have been discovered to arrest the signal transduction pathways in the malignant cells as a therapy and cure for cancer. In this work, small molecule databases were screened using the pharmacophore features of a macrocyclic inhibitor (7YS) taken as reference from the crystal structure of Axl kinase domain. Pharmacophore based virtual screening of small molecule libraries (CHEMBL32, ChemDiv, Chemspace, Mcule, MolProt, PubChem and Zinc), followed by molecular docking, molecular dynamics simulations, binding energies from MM-PBSA calculations and trajectory analysis as principal component analysis were studied. The molecular basis for the binding of macrocyclic inhibitor, ATP and seven screened hit molecules bound at Axl kinase domain in two different modes at catalytic and regulatory sites was analyzed.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836592","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}