Cell Biochemistry and Biophysics最新文献_第10页

Computational Drug Repurposing Screening Targeting Profibrotic Cytokine in Acute Respiratory Distress Syndrome. 急性呼吸窘迫综合征中靶向纤维化细胞因子的计算药物再利用筛选。

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-30 DOI: 10.1007/s12013-025-01762-x

Yong Mao, Wei Xu, Li Chen, Handi Liao

{"title":"Computational Drug Repurposing Screening Targeting Profibrotic Cytokine in Acute Respiratory Distress Syndrome.","authors":"Yong Mao, Wei Xu, Li Chen, Handi Liao","doi":"10.1007/s12013-025-01762-x","DOIUrl":"https://doi.org/10.1007/s12013-025-01762-x","url":null,"abstract":"Acute Respiratory Distress Syndrome (ARDS) is a severe lung disease with a high fatality rate and few treatment options. Targeting certain signalling pathways, notably the Transforming Growth Factor-beta (TGF-beta) signalling pathway, has emerged as a promising option for ARDS therapy. We identified TGF-beta Receptor 1 (TGFBR1) as a major target for ARDS treatment using the STRING and KEGG databases and validated TGFBR1's critical function in the TGF-beta signalling pathway, which is important in ARDS pathogenesis. To find prospective TGFBR1 inhibitors, we selected two FDA-approved medicines, Galunisertib and Vactosertib, which are established pharmacological profiles in cancer and fibrotic illnesses. Furthermore, the SwissSimilarity platform's ligand-based virtual screening revealed structurally related drugs in the DrugBank and ChEMBL databases. Among these, seven candidates were selected for further consideration. Molecular docking experiments found that DB08387 and CHEMBL14297639 had the strongest affinity for TGFBR1, creating strong hydrogen bonds at key sites. These findings point to their potential as TGFBR1 inhibitors in ARDS treatment. The pharmacokinetic screening revealed that most of the chosen compounds had favourable ADME features, with CHEMBL14297639 standing out for its low gastrointestinal absorption and limited cytochrome P450 inhibition. This study demonstrates the possibility of targeting TGFBR1 with Galunisertib, Vactosertib, and other prospective ARDS treatments. The findings lay the groundwork for additional experimental validation and the development of innovative therapeutics aimed at reducing ARDS severity.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Development of Novel α-Amylase Inhibitors: Synthesis, Molecular Docking, and Biochemical Studies. 新型α-淀粉酶抑制剂的开发：合成、分子对接和生化研究

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-29 DOI: 10.1007/s12013-025-01759-6

K Ramakrishnan, Reshma Rajan, Lenin Nachimuthu, Premkumar Jayaraj, Chandrakala A Narasimhulu, Pragney Deme, Sanjay Rajagopalan, Akella Sivaramakrishna, S Karthikeyan, Rajagopal Desikan

{"title":"Development of Novel α-Amylase Inhibitors: Synthesis, Molecular Docking, and Biochemical Studies.","authors":"K Ramakrishnan, Reshma Rajan, Lenin Nachimuthu, Premkumar Jayaraj, Chandrakala A Narasimhulu, Pragney Deme, Sanjay Rajagopalan, Akella Sivaramakrishna, S Karthikeyan, Rajagopal Desikan","doi":"10.1007/s12013-025-01759-6","DOIUrl":"https://doi.org/10.1007/s12013-025-01759-6","url":null,"abstract":"The rising prevalence of diabetes as a major non-communicable disease underscores the critical need for effective anti-diabetic agents. The new analogs designed 3a-3j were effectively synthesised and thoroughly characterised using (1H, 13C NMR, FT-IR, GCMS, and HRMS) to investigate their structural biochemical properties. The novel analogs were investigated thoroughly by in silico (molecular docking) and in vitro (anti-oxidant (DPPH, ABTS) activity, anti-inflammation (RBC), modifications of LDL and HDL, thiobarbituric substances, cholesterol efflux assay, and anti-diabetic) assays, validated for α-amylase inhibition. Enzyme inhibition results showed α-amylase IC50 values of 1.79 ± 0.12 μg for compound 3d, 1.75 ± 0.05 μg for compound 3e, and 1.53 ± 0.20 μg for the standard drug acarbose. Among the new molecules, compounds 3c and 3d exhibited the highest inhibitory activity in all performed in silico and in vitro studies. The study demonstrated that inhibitors 3a-3j bind strongly to the active site of human pancreatic α-amylase, highlighting their potential as effective inhibitors. These research findings help to improve the field of developing lead molecules for anti-diabetic agents.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

ABT263 Ameliorates Cellular Senescence, Aβ-Dependent Pathology and Cognitive Decline in Aged APP/PS1 Mice via Regulating PI3K/AKT/GSK-3β Pathways. ABT263通过调节PI3K/AKT/GSK-3β通路改善衰老APP/PS1小鼠细胞衰老、a β依赖性病理和认知能力下降。

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-28 DOI: 10.1007/s12013-025-01745-y

Zhi Tang, Xiao-Ling Wang, Yu-Xin Deng, Yan Xiao, Jian-Wei Xu, Li Wang, Xiao-Lan Qi

{"title":"ABT263 Ameliorates Cellular Senescence, Aβ-Dependent Pathology and Cognitive Decline in Aged APP/PS1 Mice via Regulating PI3K/AKT/GSK-3β Pathways.","authors":"Zhi Tang, Xiao-Ling Wang, Yu-Xin Deng, Yan Xiao, Jian-Wei Xu, Li Wang, Xiao-Lan Qi","doi":"10.1007/s12013-025-01745-y","DOIUrl":"https://doi.org/10.1007/s12013-025-01745-y","url":null,"abstract":"Alzheimer's disease is defined pathologically by the irregular buildup of senile plaques, neurofibrillary tangles, and associated neuroinflammation. As aging progresses, senescent cells gradually accumulate and significantly contribute to brain dysfunction; however, the precise mechanisms driving aging remain unclear. In the current study, ABT263, a potent senolytic drug, was administered orally to APP/PS1 mice (n = 16) for five days per cycle throughout the course of two cycles, and their behavioral tests in the Morris water maze were evaluated. Using mouse hippocampal tissue, senescence-related gene expression and SASP-associated protein expression were assessed using biochemical tests and immunohistochemical labeling. The Morris water maze test results indicated that ABT263 alleviated spatial memory impairment and reduced amyloid-β (Aβ) accumulation in APP/PS1 mice. Additionally, ABT263 treatment led to a decline in senescence-associated β-galactosidase activity, p16 senescence-related gene expression, and the expression of SASP-associated proteins, including IL-6, IL-8, and MMP-1. Further investigation revealed that ABT263 enhanced the phosphorylation levels of phosphatidylinositol-3 kinase (PI3K) (Tyr458), serine/threonine kinase AKT (S473), and glycogen synthase kinase-3β (GSK-3β) (Ser9) in APP/PS1 mice. Our results showed that ABT263 protected neurons against Aβ pathology, reduced the accumulation of senescent cells, and improved cognitive decline by enhancing PI3K/AKT/GSK-3 activity.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Correction: Cinnamaldehyde Alleviates Alveolar Epithelial Cell Injury in ALI by Inhibiting the CaMKII Pathway. 更正：肉桂醛通过抑制CaMKII通路减轻ALI患者肺泡上皮细胞损伤。

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-28 DOI: 10.1007/s12013-025-01766-7

Lei Liu, Hao Zhang, Siming Chen, Wankang Dian, Zhou Zheng

引用次数: 0

Macrophage Polarization-Based Analysis of the Role of the FOXM1/KIF20A Axis in Breast Cancer Metastasis. 基于巨噬细胞极化的FOXM1/KIF20A轴在乳腺癌转移中的作用分析

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-28 DOI: 10.1007/s12013-025-01755-w

Yuanbin Wang, Ruimin Ma, Qing Yang, Lijun Yang, Xiangli Li, Zhihao Wu

{"title":"Macrophage Polarization-Based Analysis of the Role of the FOXM1/KIF20A Axis in Breast Cancer Metastasis.","authors":"Yuanbin Wang, Ruimin Ma, Qing Yang, Lijun Yang, Xiangli Li, Zhihao Wu","doi":"10.1007/s12013-025-01755-w","DOIUrl":"https://doi.org/10.1007/s12013-025-01755-w","url":null,"abstract":"To investigate the potential molecular processes underlying the function of forkhead box M1 (FOXM1)-mediated macrophage polarization in breast cancer (BC). The expression levels of Kinesin family member 20 A (KIF20A) and FOXM1 in BC tissues and tumor-associated macrophages (TAMs) were determined using RT-qPCR. Following co-culture of macrophages with BC cells, the impact of FOXM1 on the proliferation, invasive migration ability, and epithelial-mesenchymal transition (EMT) of BC cells was assessed using cell counting kit-8, Transwell, and Western blot assays respectively. Both the chromatin immunoprecipitation (ChIP) test and the dual luciferase reporter gene assay were used to confirm the connection between FOXM1 and KIF20A. Furthermore, the effect of FOXM1 on BC cell growth in vivo was evaluated via subcutaneous tumor formation assay conducted in nude mice. BC cell growth and metastasis were aided by M2 macrophage polarization. KIF20A and FOXM1 expression levels were markedly elevated in both TAMs and BC tissues. FOXM1 drived M2 polarization of macrophages by transcriptionally activating KIF20A. In vitro studies have demonstrated that FOXM1, through its regulation of KIF20A, enhanced BC cell proliferation, migration, invasion, and EMT. The upregulation of KIF20A expression by FOXM1 promotes M2 polarization of macrophages, thereby facilitating BC cell proliferation and metastasis.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Synergistic Enhancement of Apo2L/TRAIL and DR4-Induced Apoptosis by Arsenic Trioxide in Triple-Negative Breast Cancer Cells: A Comparison to Conventional Chemotherapy. 三氧化二砷协同增强Apo2L/TRAIL和dr4诱导的三阴性乳腺癌细胞凋亡：与常规化疗的比较

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-28 DOI: 10.1007/s12013-025-01764-9

Soraya Moomivand, Mohsen Nikbakht, Ahmad Majd, Maryam Bikhof Torbati, Seyed Asadoullah Mousavi

{"title":"Synergistic Enhancement of Apo2L/TRAIL and DR4-Induced Apoptosis by Arsenic Trioxide in Triple-Negative Breast Cancer Cells: A Comparison to Conventional Chemotherapy.","authors":"Soraya Moomivand, Mohsen Nikbakht, Ahmad Majd, Maryam Bikhof Torbati, Seyed Asadoullah Mousavi","doi":"10.1007/s12013-025-01764-9","DOIUrl":"https://doi.org/10.1007/s12013-025-01764-9","url":null,"abstract":"Triple-negative breast cancer (TNBC) is an aggressive subtype lacking hormonal and HER2 receptors, making it highly resistant to treatment. Apo2L/TRAIL, a tumor necrosis factor-related ligand, induces apoptosis in cancer cells via the death receptor DR4. However, TNBC often develops resistance to TRAIL-mediated apoptosis, limiting its therapeutic potential. This study investigates whether arsenic trioxide (ATO) can overcome TRAIL resistance by modulating the Apo2L/TRAIL pathway and enhancing the effects of carboplatin (CP) and cyclophosphamide (CY). TNBC cell lines BT-20 and MDA-MB-231 were treated with ATO, CP, CY, and their combinations. Cell viability was measured using the MTT assay, while real-time PCR and Western blot analysis assessed Apo2L/TRAIL and DR4 expression. Statistical analysis was performed using ANOVA with Dunnett's post hoc test. ATO induced dose-dependent cytotoxicity in TNBC cells, which was significantly enhanced in combination treatments. The highest reductions in cell viability were observed with 3 µM ATO plus 5000 µM CP or 500 µM CY (p < 0.0001). ATO markedly upregulated Apo2L/TRAIL and DR4 at both mRNA and protein levels, with the most pronounced effects seen in ATO-CY combinations. These findings indicate that ATO sensitizes TNBC cells to TRAIL-mediated apoptosis by upregulating DR4 and Apo2L/TRAIL, while also exhibiting strong synergistic cytotoxicity with CP and CY. This highlights ATO's potential as an adjuvant therapy to improve TNBC treatment efficacy and overcome chemoresistance, warranting further clinical exploration.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

A Computational Approach for Designing a Peptide-Based Acetyl-CoA Synthetase 2 Inhibitor: A New Horizon for Anticancer Development. 设计肽类乙酰辅酶A合成酶2抑制剂的计算方法：抗癌发展的新视野。

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-27 DOI: 10.1007/s12013-025-01729-y

Musab Ali, Ernest Oduro-Kwateng, Ibrahim Oluwatobi Kehinde, Narasimham L Parinandi, Mahmoud E S Soliman

{"title":"A Computational Approach for Designing a Peptide-Based Acetyl-CoA Synthetase 2 Inhibitor: A New Horizon for Anticancer Development.","authors":"Musab Ali, Ernest Oduro-Kwateng, Ibrahim Oluwatobi Kehinde, Narasimham L Parinandi, Mahmoud E S Soliman","doi":"10.1007/s12013-025-01729-y","DOIUrl":"https://doi.org/10.1007/s12013-025-01729-y","url":null,"abstract":"Acetyl-CoA Synthetase 2 (ACSS2) has emerged as a new target for anticancer development owing to its high expression in various tumours and its enhancement of malignancy. Stressing the growing interest in peptide-derived drugs featuring better selectivity and efficacy, a computational protocol was applied to design a peptide inhibitor for ACSS2. Herein, 3600 peptide sequences derived from ACSS2 nucleotide motif were generated by classifying the 20 amino acids into six physiochemical groups. De novo modeling maintained essential binding interactions, and a refined library of 16 peptides was derived using Support Vector Machine filters to ensure proper bioavailability, toxicity, and therapeutic relevance. Structural and folding predictions, along with molecular docking, identified the top candidate, Pep16, which demonstrated significantly higher binding affinity (91.1 ± 1.6 kcal/mol) compared to a known inhibitor (53.7 ± 0.7 kcal/mol). Further molecular dynamics simulations and binding free energy calculations revealed that Pep16 enhances ACSS2 conformational variability, occupies a larger binding interface, and achieved firm binding. MM/GBSA analysis highlighted key electrostatic interactions with specific ACSS2 residues, including ARG 373, ARG 526, ARG 628, ARG 631, and LYS 632. Overall, Pep16 appears to lock the ACSS2 nucleotide pocket into a compact, rigid conformation, potentially blocking ATP binding and catalytic activity, and may serve as a novel specific ACSS2 inhibitor. Though, we urge further research to confirm and compare its therapeutic potential to existing inhibitors. We also believe that this systematic methodology would represent an indispensable tool for prospective peptide-based drug discovery.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Mechanism of Notch Signaling and Macrophages in Deep Vein Thrombosis: A Comprehensive Review. Notch信号和巨噬细胞在深静脉血栓形成中的分子机制综述

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-25 DOI: 10.1007/s12013-025-01761-y

Sisira Joy, Anusha Prasannan, Kaliyamurthi Venkatachalam, Ambika Binesh

{"title":"Molecular Mechanism of Notch Signaling and Macrophages in Deep Vein Thrombosis: A Comprehensive Review.","authors":"Sisira Joy, Anusha Prasannan, Kaliyamurthi Venkatachalam, Ambika Binesh","doi":"10.1007/s12013-025-01761-y","DOIUrl":"https://doi.org/10.1007/s12013-025-01761-y","url":null,"abstract":"Deep vein thrombosis is an acute medical condition, and the molecular basis of this etiology will be crucial in the discovery of more advanced therapies. This review has focused at the Notch signaling pathway, which plays a significant role in different physiological activities such as homeostasis, development, and disease. Also, reveal macrophage function in inflammation and thrombosis in depth, with a focus on their polarization and interaction with the endothelium during thrombosis. In this context, some essential cellular and molecular mechanisms relevant to thrombus pathogenesis, DVT aetiology and risk factors, as well as elements and composition of the Notch pathway, are covered in the end, with a focus on elements that distinguish canonical from non-canonical signaling pathways and their biological relevance to macrophages. Notch signaling has been shown to influence macrophage activation and polarization, influencing their function in thrombosis breakdown and resolution. This interplay between Notch signaling and macrophages may reveal possible treatment targets for DVT. Discuss the physiological role of Notch signaling in vascular biology, as well as how it contributes to thrombosis. The difficulties in implementing these discoveries in clinical practice are discussed, along with the status of ongoing clinical trials and experimental investigations focussing on macrophage-directed treatments and Notch inhibitors. These molecular insights synthesis provides a basis for the creation of novel strategies for the efficient management of DVT.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Correction: Chaperone-Mediated Autophagy Reactivation Protects Against Severe Acute Pancreatitis-Associated Liver Injury Through Upregulating Keap1/Nrf2 Signaling Pathway and Inhibiting NLRP3 Inflammasome Activation. 更正：伴侣介导的自噬再激活通过上调Keap1/Nrf2信号通路和抑制NLRP3炎性体激活来保护严重急性胰腺炎相关肝损伤。

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-22 DOI: 10.1007/s12013-025-01760-z

Zhongbiao Li, Yue Yu, Xihao Zhao, Yue Qu, Jiang Wang, Dianliang Zhang

引用次数: 0

Structural and Energetic Insights into the Binding of _L- and _D-Arginine Analogs with Neuropilin-1 (NRP1): Molecular Docking, Molecular Dynamics and DFT Calculations. L-和d -精氨酸类似物与Neuropilin-1 （NRP1）结合的结构和能量见解：分子对接，分子动力学和DFT计算。

IF 1.8 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-04-20 DOI: 10.1007/s12013-025-01754-x

Mahmoud A A Ibrahim, Dina E M Mohamed, Khlood A A Abdeljawaad, Alaa H M Abdelrahman, Shaban R M Sayed, Mohamed A El-Tayeb, Peter A Sidhom, Paul W Paré

{"title":"Structural and Energetic Insights into the Binding of L- and D-Arginine Analogs with Neuropilin-1 (NRP1): Molecular Docking, Molecular Dynamics and DFT Calculations.","authors":"Mahmoud A A Ibrahim, Dina E M Mohamed, Khlood A A Abdeljawaad, Alaa H M Abdelrahman, Shaban R M Sayed, Mohamed A El-Tayeb, Peter A Sidhom, Paul W Paré","doi":"10.1007/s12013-025-01754-x","DOIUrl":"https://doi.org/10.1007/s12013-025-01754-x","url":null,"abstract":"Neuropilin-1 (NRP1) is a transmembrane glycoprotein that binds numerous ligands, including vascular endothelial growth factor A (VEGFA) that stimulates blood vessel formation. Preclinical trials propose that NRP1 inhibition blocks neoplasm cell proliferation and slows tumor growth by suppressing angiogenesis. As such, VEGFA/NRP1 signaling is a potential target for carcinoma inhibition. Since arginine (Arg) regulates nutrient-responsive rapamycin signaling, which in turn regulates cell growth and metabolism, Arg, as well as simple structural variations of L- and D-Arg, were selected to study in-silico structural and energetic influences of such ligands on NRP1 signaling. Initially, AutoDock Vina1.1.2 software performance was assessed to predict binding modes of Arg analogs with NRP1 based on the available experimental data. Molecular docking and molecular dynamics (MD) simulations over 100 ns were run to inspect the potency of Arg analogs to bind with NRP1. Analog-NRP1 complex binding affinities (ΔGbinding) were evaluated using the MM/GBSA approach. Results indicated that L-/D-Agd- and L-/D-Agn-NRP1 complexes exhibited binding affinities greater than the co-crystallized L-homoarginine ligand (calc.-31.2 kcal.mol-1) with ΔGbinding values of -40.5/-40.6 and -40.0/-36.2 kcal.mol-1, respectively. Structural and energetic analyses were performed to examine further L-/D-Agd and L-/D-Agn. Quantum mechanical calculations were performed to confirm the outcomes obtained from docking computations and MD simulations.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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