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

Assessment of novel 1,2,3,4-tetrahydroquinoline-triazole hybrids compounds as inhibitors of E. coli DNA GyraseB: in vitro and in silico investigation. 新型1,2,3,4-四氢喹啉-三唑杂化合物作为大肠杆菌DNA GyraseB抑制剂的体外和计算机研究

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-21 DOI: 10.1080/07391102.2025.2503979

Bhadreshkumar K Chabhadiya, Hem N Naik, Bhavika A Mohite, Iqrar Ahmad, Harun Patel, Abdel-Basit Al-Odayni, Ramavatar Meena, Dhanji Rajani, Smita Jauhari

{"title":"Assessment of novel 1,2,3,4-tetrahydroquinoline-triazole hybrids compounds as inhibitors of E. coli DNA GyraseB: in vitro and in silico investigation.","authors":"Bhadreshkumar K Chabhadiya, Hem N Naik, Bhavika A Mohite, Iqrar Ahmad, Harun Patel, Abdel-Basit Al-Odayni, Ramavatar Meena, Dhanji Rajani, Smita Jauhari","doi":"10.1080/07391102.2025.2503979","DOIUrl":"https://doi.org/10.1080/07391102.2025.2503979","url":null,"abstract":"Ten novel 1,2,3,4-tetrahydroquinolone-triazole compounds (denoted as 6a-6j) were synthesized using click chemistry. These compounds were thoroughly characterized using various analytical techniques, such as FT-IR, mass spectrometry,1H NMR, and 13C NMR. To gather a deeper understanding regarding structural properties of the synthesized compounds, we conducted Density Functional Theory (DFT) studies employing the B3LYP/6-311G (d,p) methodology. These calculations allowed us to evaluate important properties such as the HOMO-LUMO energy gap, chemical potential (µ), electrophilicity (ω), chemical hardness (η), dipole moment (Debye), and total energy (a.u.) for the synthesized hybrids. Moving on to the practical application of these hybrids, we evaluated in vitro antimicrobial inhibitory potential against two gram-positive and two gram-negative strains, and three fungal strains. Obtained outcomes revealed a range of antibacterial activity, with some compounds exhibiting excellent to moderate efficacy. Compounds 6b and 6i showed a very good result with a MIC of 12.5 μg/mL compared to standard Ciprofloxacin (MIC 25 μg/mL), demonstrating strong antibacterial activity against E. coli among the 6a-6j compounds. Furthermore, in silico docking validated our compounds' interaction with E. coli DNA gyrase B. Further, a 200 ns simulation revealed that the promising compounds maintained stability within the binding cavity, with RMSD values below 3 Å, and exhibited reduced structural fluctuations compared to the Apo protein, as evidenced by lower average RMSF values in the ligand-protein complexes. Additionally, an in silico ADME study assessed the drug-likeness of the hybrids, offering insights for future drug development.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119669","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

AI-enhanced computational discovery of promising ALK5 inhibitors in a ultra-large chemical space library for cardiovascular Disease therapy. 在心血管疾病治疗的超大型化学空间文库中，人工智能增强的有前途的ALK5抑制剂的计算发现。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-21 DOI: 10.1080/07391102.2025.2506722

Zhaohui Xu, Jincheng Wang, Jiahui Yang, Yinqin Hu, Meng Zhang, Tianyun Shi, Qiqi Wan, Zhirui Liu, Rui Chen, Yongming Liu

{"title":"AI-enhanced computational discovery of promising ALK5 inhibitors in a ultra-large chemical space library for cardiovascular Disease therapy.","authors":"Zhaohui Xu, Jincheng Wang, Jiahui Yang, Yinqin Hu, Meng Zhang, Tianyun Shi, Qiqi Wan, Zhirui Liu, Rui Chen, Yongming Liu","doi":"10.1080/07391102.2025.2506722","DOIUrl":"https://doi.org/10.1080/07391102.2025.2506722","url":null,"abstract":"Cardiac fibrosis, characterized by excessive extracellular matrix deposition, is a critical contributor to cardiovascular diseases, including heart failure. Transforming growth factor-beta 1 signaling, especially through activin receptor-like kinase 5 (ALK5), plays a key role in cardiac fibroblast activation and fibrosis. Traditional drug discovery approaches face challenges in identifying ALK5 inhibitors. This study leverages computational methods to expedite the discovery of potential ALK5 inhibitors. An active learning model was trained to screen a vast compound library, resulting in the selection of promising candidates. Molecular fingerprint clustering analysis and the absorption, distribution, metabolism, excretion, toxicity evaluation further characterized these compounds. Machine learning-based quantitative structure - activity relationship models predicted their activity. Molecular dynamics simulations assessed binding stability in different environments. DE50349483 and DE21377883 emerged as promising candidates with potential inhibitory effects. This study showcases the power of computational methods in drug discovery, offering hope for innovative therapies in cardiac fibrosis.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-10"},"PeriodicalIF":2.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the exportin-1 inhibitors for COVID-19 and anticancer treatment. 探索新型冠状病毒出口蛋白-1抑制剂及抗癌治疗。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-21 DOI: 10.1080/07391102.2025.2503981

Tanuj Sharma, Tanmoy Mondal, Venu Venkatarame Gowda Saralamma, Md Imtaiyaz Hassan, Chang Joong Kim, Marianela Patzi Churqui, Kristina Nyström, Ketan Thombare, Mohammad Hassan Baig, Jae-June Dong

{"title":"Exploring the exportin-1 inhibitors for COVID-19 and anticancer treatment.","authors":"Tanuj Sharma, Tanmoy Mondal, Venu Venkatarame Gowda Saralamma, Md Imtaiyaz Hassan, Chang Joong Kim, Marianela Patzi Churqui, Kristina Nyström, Ketan Thombare, Mohammad Hassan Baig, Jae-June Dong","doi":"10.1080/07391102.2025.2503981","DOIUrl":"https://doi.org/10.1080/07391102.2025.2503981","url":null,"abstract":"Nuclear export protein 1, also known as XPO1, plays a crucial role in cellular homeostasis and assists in the nucleocytoplasmic transfer of ribonucleic acids (RNAs) and proteins. In addition, this nuclear export receptor is essential for the export of a variety of cargo molecules, such as proteins implicated in the immune response, tumor suppression, and cell cycle regulation. XPO1 has emerged as a promising target to disrupt the life cycles of multiple viruses and treat cancers. In our current work, we used a computational approach consisting of pharmacophore-assisted virtual screening complemented by molecular docking, molecular dynamics, and solvation-based free-energy studies to identify new inhibitors of the XPO1 protein. The identified compounds displayed highly stable RMSD plots, hydrogen bonding interactions, and relatively good binding affinities in both docking and free energy studies. These molecules were validated in vitro against SARS-CoV-2 and cancer cell lines. The study identified novel inhibitors of the XPO1 protein with both antiviral and anticancer activities.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110878","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

Enhancing thermal stability of pectinase using thermal titration molecular dynamics and density functional theory approach. 利用热滴定、分子动力学和密度泛函理论增强果胶酶的热稳定性。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-21 DOI: 10.1080/07391102.2025.2505100

Bader Huwaimel, Kareem M Younes, Hashem O Alsaab, Rami M Alzahrani, Ahmed Alobaida, Amr S Abouzied

{"title":"Enhancing thermal stability of pectinase using thermal titration molecular dynamics and density functional theory approach.","authors":"Bader Huwaimel, Kareem M Younes, Hashem O Alsaab, Rami M Alzahrani, Ahmed Alobaida, Amr S Abouzied","doi":"10.1080/07391102.2025.2505100","DOIUrl":"https://doi.org/10.1080/07391102.2025.2505100","url":null,"abstract":"Pectinase, an enzyme primarily produced from Aspergillus niger, is essential in various industrial applications. However, the enzyme's functionality at high temperatures is challenging, restricting its effectiveness and potential uses. Therefore, the present study investigated the potential of peptide binding to enhance the thermal stability of pectinase. Thermal titration molecular dynamics (MD) simulations were performed at 300, 320, 340 and 360 K to identify regions susceptible to thermal fluctuations. Based on these results, 235,200 peptide sequences were screened to target the detected unstable regions. Machine learning models predicted the peptide activity and 12 promising peptide-protein complexes were identified using docking. Binding free energy calculations showed pep-10 (-19.4 kcal/mol), pep-8 (-17.97 kcal/mol), pep-12 (-15.25 kcal/mol) and pep-6 (-9.86 kcal/mol) as the most promising candidates to improve the thermal stability. Density functional theory calculations showed that pep-12 had the lowest energy of -2365. MD simulations at 360 K for 100 ns demonstrated that pep-12 maintained the most stable conformation with root mean square deviation (0.2-0.25 nm) compared to other peptides. Quantum mechanics/molecular mechanics hybrid approach to examine the mechanism of the pep-12 complex with Pectinase. The outcomes of this study suggested that pep-12 is the most potential candidate for enhancing pectinase thermal stability.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110874","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

Pharmacophore modeling, 2D-QSAR, molecular docking and ADME studies for the discovery of inhibitors of PBP2a in MRSA. 通过药效团建模、2D-QSAR、分子对接和ADME研究发现MRSA中PBP2a抑制剂。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-19 DOI: 10.1080/07391102.2025.2507810

Fredrick Mutie Musila, Grace Wairimu Gitau, Peris Wanza Amwayi, James Munyao Kingoo, Dickson Bennet Kinyanyi, Patrisio Njiru Njeru

{"title":"Pharmacophore modeling, 2D-QSAR, molecular docking and ADME studies for the discovery of inhibitors of PBP2a in MRSA.","authors":"Fredrick Mutie Musila, Grace Wairimu Gitau, Peris Wanza Amwayi, James Munyao Kingoo, Dickson Bennet Kinyanyi, Patrisio Njiru Njeru","doi":"10.1080/07391102.2025.2507810","DOIUrl":"https://doi.org/10.1080/07391102.2025.2507810","url":null,"abstract":"Methicillin-resistant Staphylococcus aureus (MRSA) is considered to be a worldwide threat to human health and the global spread of MRSA has been associated with the emergence of different types of infections and resultant selection pressure due to exposure to many antibiotics. In the current era characterized by incessant antibiotic resistance, assessment of multiple molecular targets represents notable therapeutic opportunities in the medical and pharmaceutical industry and can aid in the discovery of novel molecules that inhibit various receptors effectively to replace the current weak antimicrobial agents. Penicillin binding protein 2a (PBP2a) of MRSA is a major determinant of resistance to β-lactam antibiotics. The activity of PBP2a is not inhibited by β-lactam antibiotics, allowing the strain to survive in the presence of β-lactams leading to resistance to β-lactam antibiotics. The study aimed at identifying potential inhibitors of PBP2a receptor of MRSA through ligand-based pharmacophore modeling, 2D-QSAR, molecular docking, ADMET screening as well as molecular dynamic (MD) simulations. The study led to the development of a satisfactory, predictive and significant 2D-QSAR model for predicting anti-MRSA activity of compounds and also led to the identification of two molecules: C21H25N7O4S2 (ChEMBL30602) and C20H17NO6S (ChEMBL304837) with favorable pharmacophore features and ADME properties with potential to bind strongly to PBP2a receptor of MRSA. MD simulation analysis showed that the interactions of C20H17NO6S (ChEMBL304837) with PBP2a over 100 ns was more stable and similar to the interaction of ceftobiprole with PBP2a and may become potential drug candidate against MRSA which has developed a lot of resistance to current antibiotics.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational study of the potential impact of WHRN protein missense SNPs on WHRN-MYO15A protein complex interaction and their association with Usher syndrome. WHRN蛋白错义snp对WHRN- myo15a蛋白复合物相互作用及其与Usher综合征关联的潜在影响的计算研究

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-19 DOI: 10.1080/07391102.2025.2507152

Fatima Ezzahra Chentoufi, Salaheddine Redouane, Abdelhamid Barakat, Houda Benrahma, Hicham Charoute

{"title":"Computational study of the potential impact of WHRN protein missense SNPs on WHRN-MYO15A protein complex interaction and their association with Usher syndrome.","authors":"Fatima Ezzahra Chentoufi, Salaheddine Redouane, Abdelhamid Barakat, Houda Benrahma, Hicham Charoute","doi":"10.1080/07391102.2025.2507152","DOIUrl":"https://doi.org/10.1080/07391102.2025.2507152","url":null,"abstract":"Usher syndrome is a rare genetic condition characterized by both hearing and vision impairment that occurs through mutations of multiple genes, including WHRN and MYO15A. In this computational work, we intend to explore how missense SNPs within the WHRN protein affect its interaction with the MYO15A protein, a crucial component of the Usher interactome. Therefore, the identification of missense SNPs that has a potential effect on the function of the WHRN protein was realized using various computational prediction tools, including VEP, SIFT, PolyPhen-2, CADD, REVEL, and Mutation Assessor. Further evaluation of the stability of mutated proteins was conducted through SDM2, MCSM, DeepDDG and CUP-SAT. We used ConSurf web server to identify conserved regions in the WHRN protein. Yasara and Haddock analysis tools were used to minimize the energy of protein 3D structures and to dock protein-protein complexes, respectively. and then the binding energy of the complexes was calculated through PRODIGY. Mutation pathogenicity prediction tools showed that in total, 18 missense SNPs, predicted as deleterious. However, a comprehensive analysis revealed that only SIX single nucleotide polymorphisms were predicted to be the most deleterious with high conservation and less stability. Furthermore, we conducted molecular dynamics analysis to fully comprehend the impact of these variations on the dynamic behavior of the WHRN-MYO15A protein complex, which revealed significant insights into the destabilizing effects of the deleterious SNPs impacting the protein's binding affinity and stability that occurs during the binding process of the WHRN-MYO15A protein complex.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-26"},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring a kinase inhibitor targeting PI3KCA mutant cancer cells. 探索一种靶向PI3KCA突变癌细胞的激酶抑制剂。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-19 DOI: 10.1080/07391102.2025.2502137

Dana F AlKharboush, Maan T Khayat, Alam Jamal, Moustafa E El-Araby, Aeshah A Awaji, Mohammad Imran Khan, Abdelsattar M Omar

{"title":"Exploring a kinase inhibitor targeting PI3KCA mutant cancer cells.","authors":"Dana F AlKharboush, Maan T Khayat, Alam Jamal, Moustafa E El-Araby, Aeshah A Awaji, Mohammad Imran Khan, Abdelsattar M Omar","doi":"10.1080/07391102.2025.2502137","DOIUrl":"https://doi.org/10.1080/07391102.2025.2502137","url":null,"abstract":"The PI3K/mTOR signaling pathway is often disrupted in human cancers, with PI3Kα being one of the most mutated kinases. There has been considerable interest in developing small-molecule inhibitors aimed at blocking the mutant PI3Kα-driven phosphatidylinositol 3-kinase (PI3K) signaling pathway as a potential treatment for cancer. In this study, we describe our effort to identify a compound, phenylacetamide-1H-imidazol-5-one (KIM-161), from our in-house oncogenic kinase-targeting inhibitors. KIM-161 showed excellent anti-proliferative activities at sub-nanomolar concentrations, primarily against mutant PI3Kα breast cancer cell lines, when compared with wild-type PI3Kα breast cancer cell lines, producing both dose- and time-dependent effects with an IC50 range of 1.42 - 0.064 µM. Next, we observed that KIM-161 was able to induce ROS production by modulating breast cancer metabolism, suggesting its broad effects on mutant PI3Kα regulated downstream pathways. We also computationally analyzed the binding interactions between KIM-161 and PI3K-alpha (PDB ID: 8EXL). Molecular docking showed that KIM-161 had a docking score of -7.44 Kcal/mol, compared to the reference compound, which had a docking score of -7.67 Kcal/mol. Moreover, molecular dynamics simulation studies demonstrated that the PI3Ka-KIM-161 complex remained stable throughout the 100 ns simulation, when compared to the PI3Ka complex with the co-crystallized inhibitor. These findings present KIM-161 as a promising lead, providing valuable insights into treatment approaches and resistance mechanisms associated with PI3K inhibitors in specific PIK3CA-mutant cancer subtypes.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101796","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 identification of potential 2-thioxothiazolidin-4-one derivatives against peroxisome proliferator-activated receptor-gamma by molecular docking, MM-GBSA, molecular dynamic simulation, and toxicity studies. 通过分子对接、MM-GBSA、分子动力学模拟和毒性研究，鉴定潜在的2-硫代噻唑烷-4- 1衍生物对抗过氧化物酶体增殖物激活受体γ。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-19 DOI: 10.1080/07391102.2025.2506713

Mahendra Gowdru Srinivasa, Manohar M, Sudeep D Ghate, Shivakiran Alva, Vinay C Sangamesh, Revanasiddappa B C

{"title":"In silico identification of potential 2-thioxothiazolidin-4-one derivatives against peroxisome proliferator-activated receptor-gamma by molecular docking, MM-GBSA, molecular dynamic simulation, and toxicity studies.","authors":"Mahendra Gowdru Srinivasa, Manohar M, Sudeep D Ghate, Shivakiran Alva, Vinay C Sangamesh, Revanasiddappa B C","doi":"10.1080/07391102.2025.2506713","DOIUrl":"https://doi.org/10.1080/07391102.2025.2506713","url":null,"abstract":"The metabolic disorder diabetes mellitus occurs when there is an inadequate level of insulin or excessive insulin resistance. There has been evidence that this pathogenesis has been approached via a different strategy. It activates homeostatic glucose and improves peripheral glucose utilization by targeting the PPAR-γ. In this regard, the present study aims to investigate 2-thioxothiazolidin-4-one derivatives (D1-15) as PPAR-γ regulators by computational approach followed by evaluation of physicochemical properties and ADMET profiles. The protein target PPAR-γ (PDB ID: 3DZY) was docked against 2-thioxothiazolidin-4-one derivatives using the glide suite. The results indicate the high binding affinity of compounds D7, D11 (-6.509 and -7.276 kcal/mol) and they were compared against standard drug rosiglitazone (-7.289 kcal/mol). MD simulation studies were also carried out at 150 ns to identify the key interactions in protein-ligand complexes in a dynamic environment not only to confirm our findings but to validate them as well. The findings indicated that certain designed compounds, namely D7 and D11, exhibited notable activity against PPAR-γ inhibitors, as evidenced by their favorable glide scores. The chosen derivatives of 2-thioxothiazolidin-4-one appear to hold promise as potential sources for advancing the development of antidiabetic agents targeting the PPAR-γ enzyme.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101800","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

Screening the absorbed active components of Danggui Sini Decoction in the treatment of diabetic peripheral neuropathy by network pharmacology combined with molecular docking and dynamics simulation. 网络药理学结合分子对接和动力学模拟，筛选当归四逆汤治疗糖尿病周围神经病变的吸收活性成分。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-18 DOI: 10.1080/07391102.2025.2505251

Qichang Xing, Wei Li, Jia Chen, Zheng Liu, Yixiang Hu, Wencan Li, Xiang Liu, Can Xiao

{"title":"Screening the absorbed active components of Danggui Sini Decoction in the treatment of diabetic peripheral neuropathy by network pharmacology combined with molecular docking and dynamics simulation.","authors":"Qichang Xing, Wei Li, Jia Chen, Zheng Liu, Yixiang Hu, Wencan Li, Xiang Liu, Can Xiao","doi":"10.1080/07391102.2025.2505251","DOIUrl":"https://doi.org/10.1080/07391102.2025.2505251","url":null,"abstract":"Diabetic peripheral neuropathy (DPN) is a prevalent and detrimental condition that can be debilitating and even fatal if not treated; however, there remains a dearth of efficacious pharmaceutical interventions for DPN. The Danggui Sini Decoction (DSD), a renowned traditional Chinese medicine prescription, has been utilized in the clinic for the treatment of DPN because of its efficacy in addressing yang deficiency and cold coagulation. However, the active components and underlying mechanisms of DSD remain unclear. In this study, we devised a conventional approach to screen the absorbed active ingredients in DSD, employing LC-MS to identify the principal active compounds of DSD in the blood of rats and then validating these components using network pharmacology for target prediction and molecular dynamics simulations for further validation. We identified 17 potentially active components in the serum and 47 main targets that might be relevant for treating DPN with DSD. These targets were associated with pathways including neuroactive ligand-receptor interaction, HIF-1, and AGE-RAGE signaling pathways, all of which are implicated in diabetic complications. Through molecular docking, we found that glycyrrhetinic acid and betulonic acid-two active components identified by LC-MS in the DSD-containing serum of rats-exhibited strong binding activities with AKT1 and STAT3. Furthermore, molecular dynamics simulations of the docking results indicated that the AKT1-glycyrrhetinic acid and AKT1-betulonic acid complexes were highly stable throughout the kinetic simulations. These findings suggest that the molecular mechanism underlying DSD treatment of DPN may involve the activation of AKT1 by glycyrrhetinic acid and betulonic acid.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093830","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 3CLpro inhibitors-modulators for human norovirus infections through an advanced virtual screening approach. 通过先进的虚拟筛选方法鉴定人类诺如病毒感染的潜在3CLpro抑制剂-调节剂。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-15 DOI: 10.1080/07391102.2025.2502672

Shovonlal Bhowmick, Tapan Kumar Mistri, Mohammad K Okla, Ibrahim A Saleh, Achintya Saha, Pritee Chunarkar Patil

{"title":"Identification of potential 3CLpro inhibitors-modulators for human norovirus infections through an advanced virtual screening approach.","authors":"Shovonlal Bhowmick, Tapan Kumar Mistri, Mohammad K Okla, Ibrahim A Saleh, Achintya Saha, Pritee Chunarkar Patil","doi":"10.1080/07391102.2025.2502672","DOIUrl":"https://doi.org/10.1080/07391102.2025.2502672","url":null,"abstract":"The present study aimed to screen small molecular compounds such as human noroviruses (HuNoV) inhibitors/modulators that could potentially be responsible for exhibiting some magnitude of inhibitory/modulatory activity against HuNoV 3CLPro. The structural similarity-based screening against the ChEMBL database is performed against known chemical entities that are presently under pre-clinical trial. After the similarity search, remaining molecules were considered for molecular docking using SCORCH and PLANTS. On detailed analyses and comparisons with the control molecule, three hits (CHEMBL393820, CHEMBL2028556, and CHEMBL3747799) were found to have the potential for HuNoV 3CLpro inhibition/modulation. The binding interaction analysis revealed several critical amino acids responsible to hold the molecules tightly at the close proximity site of the catalytic residues of HuNoV 3CLpro. Further, MD simulation study was performed in triplicate to understand the binding stability and potentiality of the proposed molecule toward HuNov 3CLpro. The binding free energy based on MM-GBSA has revealed their strong interaction affinity with 3CLpro.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078378","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