Journal of Biomolecular Structure & Dynamics最新文献

{"title":"DeepCR: predicting cytokine receptor proteins through pretrained language models and deep learning networks.","authors":"Van The Le, Juan Peter Timothy Yuune, Thi Thu Phuong Vu, Muhammad Shahid Malik, Yu-Yen Ou","doi":"10.1080/07391102.2025.2512448","DOIUrl":"https://doi.org/10.1080/07391102.2025.2512448","url":null,"abstract":"<p><p>Cytokine receptors play a pivotal role in mediating the immune response and are critical in cytokine storms, which underlie the pathogenesis of conditions such as acute respiratory distress syndrome (ARDS) and autoimmune disorders. Identifying cytokine receptors is essential for understanding their biological functions, exploring therapeutic targets, and guiding clinical interventions. Traditional biochemical methods to identify cytokine receptors are labor-intensive, costly, and time-consuming, prompting the need for more efficient alternatives. Recent advances in computational biology have enabled the use of machine learning to classify cytokine receptor proteins. Most existing approaches focused on homologous features and protein composition to classify cytokine families, but no dedicated studies have been conducted on cytokine receptor proteins. This gap presents an opportunity to develop a method specifically for classifying cytokine receptors among other membrane proteins. In this study, we present a novel classification framework combining pre-trained language models (PLMs) with a multi-window convolutional neural network (mCNN) architecture for the fast and accurate identification of cytokine receptor proteins. PLMs, such as ProtTrans and ESM variants, capture biochemical context directly from raw protein sequences, while mCNN efficiently extracts local and global sequence patterns using convolutional layers with varying window sizes. Our model achieved an AUC of 0.96 in the training as well as 0.97 and 0.93 in two independent tests, demonstrating its effectiveness in distinguishing cytokine receptors from non-cytokine receptor proteins. By eliminating the need for manual feature extraction, this approach offers a robust and scalable solution for protein classification, paving the way for its application in drug discovery and understanding cytokine-mediated diseases.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191858","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":"Integrated <i>in-silico</i> approach to explore the therapeutic potential of RNAs and druggable polyphenols to mine alternative breast cancer therapeutic strategies targeting cancer hallmarks.","authors":"Sohini Chakraborty, Satarupa Banerjee","doi":"10.1080/07391102.2025.2497465","DOIUrl":"https://doi.org/10.1080/07391102.2025.2497465","url":null,"abstract":"<p><p>Breast cancer (BC) is a global disease. A polyphenol-based therapeutic strategy is utilised to discover novel biotargets for breast cancer by assessing their drug-likeliness and toxicity. 1067 mRNAs associated with the ten initial hallmarks are retrieved from a publicly available database. However, no interacting mRNA data were found for two of the new hallmarks. The mRNAs are compared with the GEPIA database data to obtain the final 15 differentially expressed genes (DEGs) for the hallmarks. The interacting miRNAs of the DEGs are retrieved from a publicly available database. 56 druggable polyphenols are finalised for the study owing to their drug-likeliness and toxicity. Finally, a comprehensive interaction network-based analysis was carried out for the DEGs-interacting miRNAs and common druggable polyphenols. This revealed daidzein (DAI), resveratrol and 6-Gingerol; miR-663, miR-148a, miR328 and miR27b; BIRC5, CCNA2, EGFR, STAT5B and CDKN2A as significant polyphenols, miRNAs and mRNAs, respectively. Subsequently, a two-step docking approach along with molecular dynamics simulation (MDS) was also used to assess the therapeutic potential of the three polyphenols. Molecular docking revealed DAI-CCNA2 as the best fit among all the test complexes. For MDS, DAI-CCNA2 was simulated in comparison with CCNA2-Olaparib (OLA), an approved drug for breast cancer. MDS results verified DAI (the proposed drug) to be a potential candidate to combat breast cancer. Identification of druggable polyphenols using such a comprehensive <i>in-silico</i> approach can aid in providing a novel therapeutic strategy to combat the drawbacks associated with conventional therapies that can be further validated in an experimental setup.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183575","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":"Biochanin A, an isoflavone isolated from <i>Dalbergia sissoo</i> Roxb. ex DC., leaves promote ROS-mediated and caspase-dependent apoptosis in lung adenocarcinoma cells.","authors":"Anjali B Thakkar, Ramalingam B Subramanian, Vasudev R Thakkar, Sampark S Thakkar, Jignesh Prajapati, Dweipayan Goswami, Parth Thakor","doi":"10.1080/07391102.2025.2507820","DOIUrl":"10.1080/07391102.2025.2507820","url":null,"abstract":"<p><p>The objective of this study was to isolate and characterize a cytotoxic compound from the hydromethanolic extract of <i>Dalbergia sissoo</i> Roxb. ex DC. leaves using the cold percolation technique. Thin-layer chromatography was employed to isolate the cytotoxic component from the crude plant extract, and its cytotoxicity against lung adenocarcinoma (A549) cells was evaluated using the MTT assay. The structure of the isolated cytotoxic compound was determined through FTIR, NMR, UV analysis, and LC-MS/MS methods. Through comprehensive characterization, a cytotoxic compound called Biochanin A (BA) was identified, exhibiting significant anticancer activity with an IC₅₀ value of 21.92 ± 2.19 μM against A549 cells, while demonstrating lower cytotoxicity towards normal lung cells (WI-38) with an IC₅₀ value of 285.12 ± 2.19 μM. Notably, BA induced morphological changes in A549 cells, leading to apoptotic alterations and the generation of reactive oxygen species (ROS), as confirmed by multiple techniques (AO/EB, DAPI, Giemsa). <i>In silico</i> molecular docking, ADMET, MMGBSA, and molecular dynamics simulation investigations support the RT-PCR and cell biology findings. As a result, BA's molecular mechanism of action involves ROS-induced apoptosis mediated by caspases 9 and 3.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-25"},"PeriodicalIF":2.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159314","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":"Investigating the mechanism of corilagin interfering with HSV-2 replication: an <i>in vitro</i> and <i>in silico</i> analysis of the cGAS-STING pathway.","authors":"Hao Zhang, Liang Cheng, Xueshi Zhou, Renfang Chen, Feng Ju, Qigang Dong","doi":"10.1080/07391102.2025.2508347","DOIUrl":"https://doi.org/10.1080/07391102.2025.2508347","url":null,"abstract":"<p><p>Herpes simplex virus type 2 (HSV-2) represents a significant etiological agent of recurrent and symptomatic genital herpes, which poses considerable risks to public health and the global economy. The cGAS (cyclic GMP-AMP synthase) protein, a pivotal component in the cGAS/STING DNA-sensing pathway, is an appealing target for pharmacological intervention due to its essential function in the immune response against DNA viruses. Recent investigations have indicated that corilagin, a polyphenolic compound derived from plants, exhibits a wide range of antiviral properties. In this study, we utilized molecular docking, molecular dynamics simulations, MM-PBSA analysis and <i>in vitro</i> experiments to explore the binding sites and interaction dynamics of corilagin with the cGAS protein. Our findings illustrated that corilagin formed a greater number of intramolecular hydrogen bonds with the cGAS protein and displayed lower binding energy relative to the original ligand found in the Protein Data Bank (PDB), thereby suggesting its enhanced potency. <i>In vitro</i> assays confirmed that corilagin effectively mitigated the overactivation of the cGAS-STING pathway, alleviated inflammation and inhibited apoptosis in HaCaT cells, thereby demonstrating a therapeutic potential against HSV-2 infection. In summary, corilagin may act as a structural template for further modifications aimed at developing more effective cGAS inhibitors, thereby advancing the treatment of viral infectious diseases.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159317","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":"Exploring the allosteric effect of SHP2 Tyr62 phosphorylation on the emergence of acquired resistance to allosteric inhibitor SHP099.","authors":"Tingting Du, Lei Gu, Shenqian Xu, Jingfeng Zhang, Xiaoou Qiu, Wuxia Liu, Guodong Zheng, Bei Li, Bin Zhou, Minyu Li","doi":"10.1080/07391102.2025.2507815","DOIUrl":"https://doi.org/10.1080/07391102.2025.2507815","url":null,"abstract":"<p><p>The Src homology-2 (SH2)-containing phosphatase 2 (SHP2), a non-receptor protein tyrosine phosphatase, is a key regulator modulating various signaling pathways. Recent studies have revealed that phosphorylation of Tyr62 (pY62) on the N-SH2 domain of SHP2 causes the emergence of acquired resistance to the allosteric inhibitor of SHP2 (SHP099) that occupies the PTP catalytic domain. However, the allosteric mechanism underlying the insensitivity of the allosteric inhibitor SHP099 to the phosphorylated SHP2 (pSHP2) remains unexplored. In this study, multiple replica molecular dynamics (MD) simulations and the post-trajectory analyses (principal component analysis, dynamics cross-correlation matrix analysis, allosteric community analysis, and binding free energy calculations) were performed for the SHP2, pSHP2, SHP2-SHP099, and pSHP2-SHP099 complexes. MD results showed that SHP099 binding contributed to stabilize SHP2, but pY62 had a detrimental role in the stability of the pSHP2-SHP099 complex. Domain correlation analysis showed that pY62 increased the anti-correlated motions between the C-SH2 and N-SH2/PTP domains. Binding free energy calculations revealed that the protein-ligand interactions in the SHP2 - SHP099 complex were stronger than that of the pSHP2 - SHP099 complex. Further, Thr108, Phe113, and Glu250 might be the critical residues responsible for the loss of the binding affinity in the pSHP2 - SHP099 complex through a per-residue decomposition analysis and H-bond occupancy time analysis. Overall, this study may provide a mechanistic insight into the mechanism how the allosteric effect of pY62 of SHP2 on SHP099 binding.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-11"},"PeriodicalIF":2.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159315","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":"Targeting TetR-family transcription regulators for combating tetracycline resistance in resilient <i>Acinetobacter baumannii: in silico</i> identification of potent inhibitors.","authors":"Karthika Alagesan, Hemavathy Nagarajan, Balajee Ramachandran, Umashankar Vetrivel, Chitra Jeyaraj Pandian, Jeyakanthan Jeyaraman","doi":"10.1080/07391102.2025.2507812","DOIUrl":"https://doi.org/10.1080/07391102.2025.2507812","url":null,"abstract":"<p><p><i>Acinetobacter baumannii</i> stands out as a potent pathogenic microbe responsible for healthcare-associated infections characterized by elevated morbidity and mortality. This bacterium has acquired a range of mechanisms for resisting antibiotics, resulting in the emergence of strains that can withstand antibiotics from multiple classes. Effectively addressing this urgent concern requires finding ways to overcome these resistance mechanisms. In this context, our study focuses on TetR Transcriptional Factor Regulators (TetR-FTRs). It coordinates functions of tetracycline efflux pump proteins (TetA and TetR) and exert influence over metabolic pathways, quorum sensing, and biofilm formation. The primary objective is to identify potent inhibitors targeting TetR-FTRs through scaffold-based shape screening across thirteen distinct databases. A wide array of <i>in silico</i> techniques was employed, including molecular docking, molecular dynamics simulations, Swiss Similarity search, Virtual Screening, MM/GBSA analysis, ADMET assessment, PAINS assay, SIFT analysis, and MM/PBSA calculations. The initial Swiss similarity search yielded 2178 compounds for subsequent virtual screening, with the application of PAINS analysis rigorously pruning the list, eliminating 14 false positive hits. Further refinement through SIFT approach discriminated closely related interacting compounds into three distinct clusters - ChemBridge5963254, BDH33906706, and ZINC000013607604, which fulfilled all SIFT criteria. Comparative evaluation against reference compounds revealed favorable glide scores, lower binding free energies, and interactions with crucial active site residue Hsd128-Mg²⁺. Molecular dynamics simulations consistently exhibited stable binding for these clusters in contrast to reference compounds. Our analysis underscores three specific compounds, namely ChemBridge5963254, BDH33906706, and ZINC000013607604, as promising candidates for addressing tetracycline resistance and combating <i>A. baumannii</i> infections.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-26"},"PeriodicalIF":2.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150517","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 simulation guided prediction of the inhibitory effect of curcumin, diallyl sulfide and its conjugates on ALDH1A1 to target breast cancer stem cells (BCSCs).","authors":"Kanchan Gairola, Gagandeep Singh, Ananya Bahuguna, Rohit Pujari, Rajesh Kumar Kesharwani, Shiv Kumar Dubey","doi":"10.1080/07391102.2025.2506720","DOIUrl":"https://doi.org/10.1080/07391102.2025.2506720","url":null,"abstract":"<p><p>. Despite the significant advancements in clinical and laboratory research, breast cancer remains a formidable challenge due to its high incidence, recurrence and mortality rate. The emerging paradigm emphasizes the pivotal role of cancer stem cells in compelling cancer initiation and recurrence attributed to the resistance against conventional radio and chemotherapy, thereby leading to poor prognosis and disease relapse post-treatment. Aldehyde dehydrogenase (ALDH1A1) is the putative stemness biomarker in breast cancer stem cells. It has been attributed to drug resistance in chemotherapy, especially against the drugs derived from aldehydic intermediate in action mechanism, cell differentiation and oxidative stress response. Since time immemorial, natural products have been employed in traditional medicine systems for their therapeutic and chemopreventive properties. Curcumin, an active polyphenol present in turmeric, plays a significant role in impeding the growth of BCSCs. However, the clinical efficacy of curcumin is restrained due to its poor bioavailability, limited absorption, rapid metabolism, and systemic elimination. To address this challenge, efforts have been directed towards synthesizing curcumin conjugates with diallyl sulfide to enhance its bioavailability. Computational tools such as molecular docking, molecular dynamics simulations and end-state MMGBSA binding free-energy calculations were employed to predict the optimal binding of curcumin conjugates with ALDH1A1 and provide valuable insights into their potential binding affinity and therapeutic efficacy. The enhanced bioavailability of curcumin may be attributed to the enhanced therapeutic activity against the BCSCs. Furthermore, synthesizing curcumin conjugates holds promise in cancer Chemoprevention. .</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150514","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":"Noncovalent interaction analysis and bioactivity evaluation of a novel chlorinated Schiff compound.","authors":"A H Udaya Kumar, Mahesha, K J Pampa, V Harohally Nanishankar, Sneha Yadav, Ragesh Nath R, Shivaraju Harikaranahalli Puttaiah, N K Lokanath","doi":"10.1080/07391102.2025.2504007","DOIUrl":"https://doi.org/10.1080/07391102.2025.2504007","url":null,"abstract":"<p><p>Intermolecular interactions play a significant role in the area of pharmaceuticals. Hence, there is an increasing trend towards the analysis of noncovalent interactions of active molecules to investigate the correlation between structure and properties. In this context, new Schiff base compound <i>2,4-dichloro-6-(((4-chlorobenzyl)imino)methyl)phenol</i> has been prepared by condensation of 3,5-dichloro-2-hydroxybenzaldehyde and (4-chlorobenzyl)methenamine. The single crystals of Schiff base were obtained by the slow evaporation method. To investigate the solid-state behaviour and noncovalent interactions, X-ray diffraction analysis was performed. The crystal packing pattern is evident that noncovalent C-H‧‧‧O, C-H‧‧‧π and π‧‧‧π interactions result in 2-D supramolecular architecture. Meanwhile, computational studies were carried out to rationalize the strength and nature of different types of interactions involved in the crystal packing. Hirshfeld surface and enrichment ratio analyses provide the quantitative contribution of each intermolecular interaction. The intramolecular hydrogen bonding environment is well supported qualitatively by QTAIM and NCI isosurface. Based on the optimized ground state geometry by density functional theory, the physical and chemical properties of the compound were investigated. To acquire a more profound comprehension of the interaction of the ligand with the protein and their binding affinity, <i>in-silico</i> docking and molecular dynamic simulation studies were performed. It has also been observed that the Schiff base compound unveiled antibacterial activity against the bacterial species MRSA.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142488","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 new strategy based on drug-linker-nanocarrier interactions to design new HIV-1 non-nucleoside reverse transcriptase inhibitors.","authors":"Mehdi Yoosefian, Elnaz Mirhaji, Arefeh Esmaeili","doi":"10.1080/07391102.2025.2507814","DOIUrl":"https://doi.org/10.1080/07391102.2025.2507814","url":null,"abstract":"<p><p>The development of effective non-nucleoside inhibitors targeting HIV-1 reverse transcriptase (RT) remains a persistent challenge in AIDS research, particularly in overcoming drug-induced mutations. This study focuses on harnessing the potential of Rilpivirine (RPV), a widely recognized non-nucleoside inhibitor, as a foundational structure for designing and synthesizing inhibitors with superior anti-HIV-1 activities compared to RPV. Through strategic conjugation of RPV to molecular umbrellas using diverse linkers such as BSOCOES, DSP, and EGS, a novel series of potent non-nucleoside inhibitors is crafted. Guided by a structure-based drug design approach, this study unveils a new series of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Comprehensive molecular analyses reveal extensive interactions between these NNRTIs and the RT inhibitor-binding pocket, confirming their superior antiviral efficacy against the wild-type virus when compared to RPVs. The innovative strategy employed in this research, focusing on drug-linker-nanocarrier interactions, introduces a promising avenue for designing and developing robust HIV-1 RT inhibitors with potential clinical applications. The findings emphasize the approach's potential for addressing challenges posed by drug-resistant mutations, opening new possibilities for advancing antiretroviral therapy.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136303","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":"Identification of potential IL4I1 inhibitors through structure-based virtual screening and molecular dynamics simulations.","authors":"Xuan Zhao, Jing Chen, Mengyi Shan, Peng Sun, XinHao Qu, Lu-Ping Qin, Gang Cheng","doi":"10.1080/07391102.2025.2501666","DOIUrl":"https://doi.org/10.1080/07391102.2025.2501666","url":null,"abstract":"<p><p>Interleukin-4-induced gene 1 (IL4I1) is an L-phenylalanine oxidase. As the primary enzyme responsible for degrading tryptophan, IL4I1 generates indole metabolites and kynurenic acid, which act as crucial endogenous ligands to activate the aryl hydrocarbon receptor (AHR). This activation enhances tumor survivability while suppressing the body's anti-tumor immune response. Consequently, IL4I1 is now recognized as a promising new target for drug development in the realm of cancer immunomodulation. In this study, we employed a strategy combining AlphaFold2 with molecular dynamics (MD) simulations to model receptor conformations our docking model achieved a regression fit with an R² coefficient of 0.34, providing a robust framework for structure-based virtual screening aimed at identifying potential IL4I1 inhibitors. We then applied this structure-based virtual screening method to a compound library. After further MD simulation and following Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) calculation of binding free energy and ADMET analysis, five candidate IL4I1 inhibitors were obtained. This study provides an effective in silico approach for the identification of IL4I1 inhibitors and offers a valuable reference for the virtual screening of inhibitors targeting other proteins without known structures.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-24"},"PeriodicalIF":2.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135891","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}