Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Synthesis, antimicrobial properties and <i>in silico</i> evaluation of coumarin derivatives mediated by 1,4-dibromobutane.","authors":"Eunice N Tiakouang, Monique B Ewonkem, Jean O Moto, Abel I Adjieufack, Pascaline M Deussom, Michel A Mbock, Emmanuel H Ngeufa, Alfred F A Toze, Duplex J Wansi","doi":"10.1080/07391102.2024.2321507","DOIUrl":"10.1080/07391102.2024.2321507","url":null,"abstract":"<p><p>In this study, monobrominated coumarins (<b>5</b>-<b>6</b>) and bis-coumarins (<b>7</b>-<b>9</b>) were synthesized from 3-carboxylic coumarin and 7-hydroxy-4-methyl coumarin using 1,4-dibromobutane as a binding agent, according to the synthesis procedures described in the literature. Amongst these coumarins, three are new compounds: monobrominated coumarin <b>5</b> and bis-coumarins <b>7</b> and <b>9</b>. The structures of the synthesized coumarins were confirmed by FTIR, NMR and HRMS-ESI. <i>In vitro</i> antimicrobial evaluation of these coumarins against strains of twelve bacteria and four fungi revealed their bactericidal and fungicidal properties, with increased antibacterial activity for monocoumarins and improved antifungal activity for bis-coumarins. It was also found that the antibacterial activity was enhanced by the etheric bond, Br atom and alkyl chain and reduced by the ester bonds at position 3 of the pyrone ring or an additional coumarin unit, while the antifungal activity was reinforced by ester bonds and deactivated by the Br atom. For the first time, the <i>in silico</i> investigations of such coumarins were carried out and it was observed that they are less toxic, suitable for oral administration with good permeability through cell membrane, are able to circulate freely in the bloodstream and cross Blood-Brain-Barriers. Moreover, their molecular docking in DNA indicated stable coumarin-DNA complexes with good scores. The results of molecular dynamics simulations performed for 200 ns revealed the rigidity and stability of bis-coumarins (<b>7-9</b>) in the DNA binding pocket and predict that they are potent binders.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6123-6136"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972044","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":"Whole genome based identification of BAHD acyltransferase gene involved in piperine biosynthetic pathway in black pepper.","authors":"M A Fayad, Sona Charles, S Shelvy, T E Sheeja, K Sangeetha, U B Angadi, Gitanjali Tandon, Mir Asif Iquebal, Sarika Jaiswal, Dinesh Kumar","doi":"10.1080/07391102.2024.2313164","DOIUrl":"10.1080/07391102.2024.2313164","url":null,"abstract":"<p><p>Black pepper (<i>Piper nigrum</i> L.), a crop of the genus Piper, is an important spice that has both economic and ecological significance. It is widely regarded as the \"King of Spices\" because of its pungency, attributed to the presence of piperine. BAHD acyl transferase, the crucial enzyme involved in the final step in piperine biosynthesis was the focus of our study and the aim was to identify the candidate isoform involved in biosynthesis of piperine. Reference genome-based analysis of black pepper identified six BAHD-AT isoforms and mapping of these sequences revealed that the isoforms were situated on six distinct chromosomes. By using specific primers for each of these transcripts, qPCR analysis was done in different tissues as well as berry stages to obtain detectable amplification products. Expression profiles of isoforms from chromosome 6 correlated well with piperine content compared to other five isoforms, across tissues and was therefore assumed to be involved in biosynthesis of piperine. In addition to this, we could also identify the binding sites of MYB transcription factor in the cis-regulatory regions of the isoforms. We also used <i>in-silico</i> docking and molecular dynamics simulation to calculate the binding free energy of the ligand and confirmed that among all the isoforms, BAHD-AT from chromosome 6 had the lowest free binding energy and highest affinity towards the ligand. Our findings are expected to aid the identification of new genes connecting enzymes involved in the biosynthetic pathway of piperine, which will have major implications for future research in metabolic engineering.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5806-5818"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722768","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":"Chinese herb couple against diabetes: integrating network pharmacology and mechanism study.","authors":"Jing Li, Nini Jia, Mengyao Cui, Yaqing Li, Dayuan Jiang, Xiaoqin Chu","doi":"10.1080/07391102.2024.2314263","DOIUrl":"10.1080/07391102.2024.2314263","url":null,"abstract":"<p><p>Cassia twig is a dry twig of <i>Cinnamomum cassia Presl</i>, a <i>Lauraceae</i> plant. Astragalus L is one of the largest genuses of flowering plants in the <i>Leguminosae</i> family. Roots of A. membranaceus Bge. var. mongholicus (Bge.) Hsiao, A. membranaceus (Fisch.) Bge. Chinese herb couple refers to the matching of two herbs in pairs, mostly with synergistic effects or toxicity reduction. This Chinese herb couple (Cassia twig-Astragalus) come from the classic famous book \"Zhang Xichun's book on Chinese herb couple\", which is widely used to treat diabetes. Moreover, both Cassia twig and Astragalus belong to the homology of medicine and food. However, its mechanism is still unclear. The study identified the effective components of Cassia twig-Astragalus by UPLC-Q-TOF-MS/MS and investigated the mechanism of Cassia twig-Astragalus in treating diabetes by virtue of network pharmacology, molecular docking and experimental verification. Firstly, based on UPLC-Q-TOF-MS/MS and network pharmacology, a total of 10 active ingredients of Astragalus and 6 active ingredients of Cassia twig were screened, and a total of 13 key targets were obtained. There were 64 targets at the intersection of Cassia twig-Astragalus with diabetes, mainly including IL-17, TNF, NF-κβ, AGE-RAGE signaling pathway, etc. It mainly involves the response of cells to insulin stimulation, the response to insulin and the positive regulation of cell adhesion. Secondly, molecular docking results showed that quercetin has good binding activities with AKT1 and TNF. Calycosin has good binding activities with AKT1, TNF and CAV1. Formononetin has good binding activities with TNF and IL-6. Isorhamnetin has good binding activities with AKT1, TNF and IL-6. Finally, the animal experiments showed that Cassia twig-Astragalus could improve the body weight, blood glucose and glucose tolerance in diabetic rats. After the intervention with Cassia twig-Astragalus, the inflammatory factors (IL-10, TNF-α, IL-6) were significantly improved in diabetic rats, which also effectively reduced TG and TC.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5982-5998"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722762","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":"Discovering Lassa virus nucleoprotein inhibitors via in silico drug repositioning approach.","authors":"Handan Şimşek, Şeref Gül","doi":"10.1080/07391102.2024.2427370","DOIUrl":"10.1080/07391102.2024.2427370","url":null,"abstract":"<p><p>Lassa fever, caused by the zoonotic Lassa virus (LASV), poses a significant health threat in Africa, leading to thousands of infections and deaths annually and has the potential to spread to other parts of the world. Despite the urgency for effective treatments, there are currently no approved drugs or vaccines for Lassa fever. LASV possesses a unique negative-sense RNA genome, and NP plays a crucial role in viral assembly and infection. Crystallographic analysis reveals distinct domains in NP, with the N-terminal domain involved in RNA binding and the C-terminal domain exhibiting exoribonuclease activity, suppressing type I interferon-mediated immune responses. This study explores the potential of repurposing existing FDA-approved drugs by targeting the N-terminal domain of LASV's nucleoprotein (NP). Docking simulations and molecular dynamics experiments were conducted, revealing promising interactions between NP and widely used and well tolerated drugs such as metacycline, eltrombopag, glimepiride, lurasidone, paliperidone, prednisone, doxazosin, flavin mononucleotide, and pimozide. These drugs exhibited stable binding throughout 100 ns simulations, with interactions resembling those observed with the natural ligand, dTTP. Binding free energy calculations identified key amino acids, particularly Phe176 and Arg300, as crucial for drug-NP interactions. Notably, drugs like FMN, prednisone, metacycline, pimozide, and glimepiride displayed binding affinities comparable to dTTP, suggesting their potential as LASV inhibitors. The study underscores the importance of further experimental and clinical validation of these in silico findings. The identified drugs present promising candidates for potential treatments for Lassa fever, addressing the current gap in approved therapeutics for this life-threatening infectious disease.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6316-6336"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621292","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":"Molecular dynamics simulation as a promising approach for computational study of liquid crystal-based aptasensors.","authors":"Hamed Zahraee, Seyed Shahriar Arab, Zahra Khoshbin, Seyed Mohammad Taghdisi, Khalil Abnous","doi":"10.1080/07391102.2024.2315326","DOIUrl":"10.1080/07391102.2024.2315326","url":null,"abstract":"<p><p>As a potent computational methodology, molecular dynamics (MD) simulation provides advantageous knowledge about biological compounds from the molecular viewpoint. In particular, MD simulation gives exact information about aptamer strands, such as the short synthetic oligomers, their orientation, binding sites, folding-unfolding state, and conformational re-arrangement. Also, the effect of the different chemicals and biochemicals as the components of aptamer-based sensors (aptasensors) on the aptamer-target interaction can be investigated by MD simulation. Liquid crystals (LCs) as soft substances with characteristics of both solid anisotropy and liquid fluidity are new candidates for designing label-free aptasensors. To now, diverse aptasensors have been developed experimentally based on the optical anisotropy, fluidity, and long-range orientational order of LCs. Here, we represent a computational model of an LC-based aptasensor through a detailed MD simulation study. The different parameters are defined and studied to achieve a comprehensive understanding of the computational design of the LC-based aptasensor, including the density of LCs, their orientation angle, and lognormal distribution in the absence and presence of aptamer strands, both aptamer and target molecules with various concentrations, and interfering substance. As a case study, the tobramycin antibiotic is considered the target molecule for the computational model of the LC-based aptasensor.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6803-6815"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722730","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":"A novel deep learning model for diabetic retinopathy detection in retinal fundus images using pre-trained CNN and HWBLSTM.","authors":"S V Hemanth, Saravanan Alagarsamy, T Dhiliphan Rajkumar","doi":"10.1080/07391102.2024.2314269","DOIUrl":"10.1080/07391102.2024.2314269","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is a global visual indicator of diabetes that leads to blindness and loss of vision. Manual testing presents a more difficult task when attempting to detect DR due to the complexity and variances of DR. Early detection and treatment prevent the diabetic patients from visual loss. Also classifying the intensity and levels of DR is crucial to provide necessary treatment. This study develops a novel deep learning (DL) approach called He Weighted Bi-directional Long Short-term Memory (HWBLSTM) with an effective transfer learning technique for detecting DR from the RFI. The collected fundus images initially undergo preprocessing to improve their quality, which includes noise removal and contrast enhancement using a Hybrid Gaussian Filter and probability density Function-based Gamma Correction (HGFPDFGC) technique. The segmentation procedure divides the image into subgroups and is crucial for accurate detection and classification. The segmentation of the study initially removes the optical disk (OD) and blood vessels (BVs) from the preprocessed images using mathematical morphological operations. Next, it segments the retinal lesions from the OD and BV removed images using the Enhanced Grasshopper Optimization-based Region Growing Algorithm (EGORGA). Then, the features from the segmented retinal lesions are learned using a Squeeze Net (SQN), and the dimensionality reduction of the extracted features is done using the Modified Singular Value Decomposition (MSVD) approach. Finally, the classification is performed by employing the HWBLSTM approach, which classifies the DR abnormalities in datasets as non-DR (NDR), non-proliferative DR (NPDR), moderate NPDR (MDNPDR), and severe DR, also known as proliferative DR (PDR). The proposed approach is implemented on APTOS as well as MESSIDOR datasets. The outcomes proved that the proposed technique accurately identifies the DR with minimal computation overhead compared to the existing approaches.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6455-6473"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905721","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":"Repurposing naproxen as a potential nucleocapsid antagonist of beta-coronaviruses: targeting a conserved protein in the search for a broad-spectrum treatment option.","authors":"Reza Valadan, Reza Alizadeh-Navaei, Milad Lagzian, Majid Saeedi, Fatemeh Roozbeh, Akbar Hedayatizadeh-Omran, Massoud Amanlou","doi":"10.1080/07391102.2024.2321245","DOIUrl":"10.1080/07391102.2024.2321245","url":null,"abstract":"<p><p>Ongoing mutations in the coronavirus family, especially beta-coronaviruses, raise new concerns about the possibility of new unexpected outbreaks. Therefore, it is crucial to explore new alternative treatments to reduce the impact of potential future strains until new vaccines can be developed. A promising approach to combat the virus is to target its conserved parts such as the nucleocapsid, especially <i>via</i> repurposing of existing drugs. The possibility of this approach is explored here to find a potential anti-nucleocapsid compound to target these viruses. 3D models of the N- and C-terminal domains (CTDs) of the nucleocapsid consensus sequence were constructed. Each domain was then screened against an FDA-approved drug database, and the most promising candidate was selected for further analysis. A 100 ns molecular dynamics (MD) simulation was conducted to analyze the final candidate in more detail. Naproxen was selected and found to interact with the N-terminal domain <i>via</i> conserved salt bridges and hydrogen bonds which are completely conserved among all Coronaviridae members. MD analysis also revealed that all relevant coordinates of naproxen with N terminal domain were kept during 100 ns of simulation time. This study also provides insights into the specific interaction of naproxen with conserved RNA binding pocket of the nucleocapsid that could interfere with the packaging of the viral genome into capsid and virus assembly. Additionally, the <i>in-vitro</i> binding assay demonstrated direct interaction between naproxen and recombinant nucleocapsid protein, further supporting the computational predictions.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"6700-6715"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972042","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":"Aromatase inhibitors identified from <i>Saraca asoca</i> to treat infertility in women with polycystic ovary syndrome via <i>in silico</i> and <i>in vivo</i> studies.","authors":"Kuppachi Himaja, Kandasamy Veerapandiyan, Balasundaram Usha","doi":"10.1080/07391102.2024.2310793","DOIUrl":"10.1080/07391102.2024.2310793","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a widely occurring metabolic disorder causing infertility in 70%-80% of the affected women. <i>Saraca asoca</i>, an ancient medicinal herb, has been shown to have therapeutic effects against infertility and hormonal imbalance in women. This study was aimed to identify new aromatase inhibitors from <i>S. asoca</i> as an alternative to the commercially available ones via <i>in silico</i> and <i>in vivo</i> approaches. For this, 10 previously reported flavonoids from <i>S. asoca</i> were chosen and the pharmacodynamic and pharmacokinetic properties were predicted using tools like Autodock Vina, GROMACS, Gaussian and ADMETLab. Of the 10, procyanidin B2 and luteolin showed better interaction with higher binding energy when docked against aromatase (3S79) as compared to the commercial inhibitor letrozole. These two compounds showed higher stability in molecular dynamic simulations performed for 100 ns. Molecular mechanics Poisson-Boltzmann surface analysis indicated that these compounds have binding free energy similar to the commercial inhibitor, highlighting their great affinity for aromatase. Density functional theory analysis revealed that both compounds have a good energy gap, and ADMET prediction exhibited the drug-likeness of the two compounds. A dose-dependent administration of these two compounds on zebrafish revealed that both the compounds, at a lower concentration of 50 µg/ml, significantly reduced the aromatase concentration in the ovarian tissues as compared to the untreated control. Collectively, the <i>in silico</i> and <i>in vivo</i> findings recommend that procyanidin B2 and luteolin could be used as potential aromatase inhibitors for overcoming infertility in PCOS patients with estrogen dominance.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5645-5660"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691881","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":"Design of human ACE2 mimic miniprotein binders that interact with RBD of SARS-CoV-2 variants of concerns.","authors":"Neeraj K Gaur, Zeenat Khakerwala, Ravindra D Makde","doi":"10.1080/07391102.2024.2310789","DOIUrl":"10.1080/07391102.2024.2310789","url":null,"abstract":"<p><p>The world of medicine demands from the research community solutions to the emerging problem of SARS-CoV-2 variants and other such potential global pandemics. With advantages of specificity over small molecule drugs and designability over antibodies, miniprotein therapeutics offers a unique solution to the threats of rapidly emerging SARS-CoV-2 variants. Unfortunately, most of the promising miniprotein binders are <i>de novo</i> designed and it is not viable to generate molecules for each new variant. Therefore in this study, we demonstrate a method for design of miniprotein mimics from the interaction interphase of human angiotensin converting enzyme 2 (ACE2). ACE2 is the natural interacting partner for the SARS-CoV-2 spike receptor binding domain (RBD) and acts as a recognition molecule for viral entry into the host cells. Starting with ACE2 N-terminal triple helix interaction interphase, we generated more than 70 miniprotein sequences. Employing Rosetta folding and docking scores we selected 10 promising miniprotein candidates amongst which 3 were found to be soluble in lab studies. Further, using molecular mechanics (MM) calculations on molecular dynamics (MD) trajectories we test interaction of miniproteins with RBD from various variants of concern (VOC). Presently, we report two key findings; miniproteins in this study are generated using less than 10 lab testing experiments, yet when tested through <i>in-vitro</i> experiments, they show submicro to nanomolar affinities towards SARS-CoV-2 RBD. Also in simulation studies, when compared with previously developed therapeutics, our miniproteins display remarkable ability to mimic ACE2 interphase; making them an ideal solution to the ever evolving problem of VOCs.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5999-6011"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691883","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":"<i>In silico</i> investigations and molecular insights for designing tRNA-encoded peptides as potential therapeutics for targeting over-expressed receptors in breast cancer.","authors":"Pallavi M Shanthappa, Nidheesh Melethadathil","doi":"10.1080/07391102.2024.2314748","DOIUrl":"10.1080/07391102.2024.2314748","url":null,"abstract":"<p><p>tRNA- Encoded Peptides (tREPs) have recently been discovered as new functional peptides and hold promise as therapeutics for anti-parasitic applications. In this study, <i>in silico</i> investigations were conducted to design tRNA-encoded peptides with the potential to target over-expressed receptors in breast cancer cells. tRNA genes were translated into corresponding peptides (tREPs) using computational tools. The tREPs, which were predicted as anticancer peptides, were then screened for various ADMET properties. Molecular docking studies were conducted for three cancer target receptors, the Estrogen Receptor (ER), Peroxisome Proliferator-Activated Receptor (PPAR) and the Epidermal Growth Factor Receptor (EGFR). Based on the docking results, specific tREPs were screened and molecular dynamics simulations were performed, and the binding energies were further explored using MMPBSA calculations. The peptide Pep1 (DWIAWRHHNDIVSWLTCGPRFKSWS) and Pep2 (GFIAWWSRHLELAQTRFKSWWS) exhibited a good binding affinity against the Estrogen Receptor (ER) and the Peroxisome Proliferator-Activated Receptor Alpha (PPAR) cancer target. The Pep1-ER and Pep1-PPAR complex maintained an average of two hydrogen bonds throughout the simulation and demonstrated a higher negative binding free energy of -72.27 kcal/mol and -65.16 kcal/mol respectively, as calculated by MMPBSA. Therefore, the tREPs designed as anticancer peptides in this study provide novel approaches for potential anticancer therapeutic modalities.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5900-5916"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706887","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}