Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Phytochemical profiling, <i>in vitro</i> analysis for anti-inflammatory, immunomodulatory activities, structural elucidation and <i>in silico</i> evaluation of potential selective COX-2 and TNF-α inhibitor from <i>Hydrilla verticillata</i> (L.f.) Royle.","authors":"Bhagyeswari Behera, Rajesh Kumar Meher, Showkat Ahmad Mir, Binata Nayak, Kunja Bihari Satapathy","doi":"10.1080/07391102.2023.2283871","DOIUrl":"10.1080/07391102.2023.2283871","url":null,"abstract":"<p><p><i>Hydrilla verticillata</i> (L.f.) Royle is a perennial aquatic plant, which exhibits nutritional as well as therapeutic properties. The present study has been carried out to evaluate anti-inflammatory and immunomodulatory activities along with <i>in silico</i> evaluation of potential selective COX-2 and TNF-α inhibitors from methanolic extract of <i>H. verticillata</i> (L.f.) Royle. The potential therapeutic compounds have been identified by high-resolution GC-MS analysis. Its capacity to inhibit inflammatory responses using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells has been explored. The anti-inflammatory properties of the plant extract were investigated by inhibiting inducible nitric oxide (NO) synthase and reduced NO generation driven by LPS on stimulated RAW 264.7 macrophage cells. Further investigation for the underlying molecular mechanism of the anti-inflammatory activity of plant extract has been carried out by molecular docking and molecular dynamics simulation approaches with COX-2 and TNF-α inhibitors ability against the most potent phytocompound phytol from the plant extract. To evaluate whether the extract causes any toxicity, the cytotoxicity test has been carried out with the Human embryonic kidney cell line (Hek-293), Mouse fibroblast (L929), human mesenchyme stem cells (hMSCs) and human breast epithelial cell line (MCF-10a). Ultimately, our findings suggest that the plant extract have great potential to reduce inflammation without causing any toxicity to normal cell.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"859-873"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451499","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":"Probable targets and mechanism of ginsenoside Rg1 for non-alcoholic fatty liver disease: a study integrating network pharmacology, molecular docking, and molecular dynamics simulation.","authors":"Danni Wang, Jia Zhang, Haifeng Dai, Kexin Tong, Mingjing Chen, Jiayi Peng, Wenxiang Huang","doi":"10.1080/07391102.2023.2289045","DOIUrl":"10.1080/07391102.2023.2289045","url":null,"abstract":"<p><p>Ginsenoside Rg1 (GRg1), a key bioactive component of medicinal herbs, has shown beneficial effects on non-alcoholic fatty liver disease (NAFLD) and numerous other conditions. Nevertheless, the specific targets that are actively involved and the potential mechanisms underlying NAFLD treatment remain unclear. This study aimed to elucidate the therapeutic effects and mechanism of GRg1 in alleviating NAFLD using a combined approach of network pharmacology and molecular biology validation. The analysis yielded 294 targets for GRg1 and 1293 associated with NAFLD, resulting in 89 overlapping targets. Through protein-protein interactions (PPI) network topology analysis, 10 key targets were identified. Upon evaluating the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis, GRg1 may exert therapeutic effects on NAFLD by negatively regulating the apoptotic process, insulin and endocrine resistance, the AGE-RAGE signaling pathway in diabetic complications, and the Estrogen, PI3K/Akt, and MAPK pathways. The three differential gene targets for Akt1, EGFR, and IGF1 were identified through the compound-target network in conjunction with the aforementioned methods. The molecular docking and molecular dynamics (MD) simulations showed that AKT1 and EGFR had a strong binding affinity with GRg1. Overall, our findings point to a novel therapeutic strategy involving NAFLD, with further <i>in vivo</i> and <i>in vitro</i> studies promising to deepen our comprehension and validate its potential advantages.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"932-945"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460135","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":"Rational design of thiazolidine-4-one-gallic acid hybrid derivatives as selective partial PPARγ modulators: an in-silico approach for type 2 diabetes treatment.","authors":"Aryan, B Babu, S Divakar, B Gowramma, Srikanth Jupudi, Jagdish Chand, Vishnu Malakar Kumar","doi":"10.1080/07391102.2023.2283161","DOIUrl":"10.1080/07391102.2023.2283161","url":null,"abstract":"<p><p>Type 2 diabetes mellitus is a bipolar metabolic disorder characterized by abnormalities in insulin production from β-cells and insulin resistance. Thiazolidinediones are potent anti-diabetic agents that act through the modulation of the peroxisome proliferator-activated receptor γ (PPARγ), a nuclear receptor. However, their full agonistic activity leads to severe side effects by stabilizing Helix12 through strong hydrogen bonding with the TYR473 residue. Partial and selective PPARγ modulators (GW0072, GQ16, VSP-51, MRL-20, MBX-213, INT131) have demonstrated superior results compared to full agonists without causing adverse effects, as reported in existing data. To address this uncertainty and advance therapeutic options, we identified and designed a novel class of compounds (A1-A23) based on a hybrid structure combining phenolic and Thiazolidine-4-one's moieties. Our rational drug design strategy incorporated structural-activity relationship principle, and validated the docking studies through calculated the root mean square deviation. Additionally, we conducted molecular docking, binding energy, molecular dynamics simulations, and post-molecular dynamics calculations to evaluate the dynamics behavior between the ligands and protein. The selected ligands demonstrated highly favorable docking scores and binding energies, comparable to the co-crystal (rosiglitazone) such as A12 (-13.9 kcal/mol and -86.2 kcal/mol), A1 (-11.1 kcal/mol and -79.5 kcal/mol), A13 (-11.3 kcal/mol and -91.4 kcal/mol), and the co-crystal itself (-9.8 kcal/mol and -76 kcal/mol), respectively. Finally, the MD revealed that, the selected ligands were equally contributed for stabilization of Helix12 and β-sheets. It was concluded, the designed ligands (A12, A1, and A13) exhibited weaker hydrogen-bond interactions with specific residue TYR473 which partially modulated the PPARγ protein.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"694-708"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299176","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":"De novo drug designing coupled with brute force screening and structure guided lead optimization gives highly specific inhibitor of METTL3: a potential cure for Acute Myeloid Leukaemia.","authors":"Manisha Ganguly, Radhika Gupta, Amlan Roychowdhury, Ditipriya Hazra","doi":"10.1080/07391102.2023.2291162","DOIUrl":"10.1080/07391102.2023.2291162","url":null,"abstract":"<p><p>Expression of METTL3, a SAM dependent methyltransferase, which deposits m6A on mRNA is linked to poor prognosis in Acute Myeloid Leukaemia and other type of cancers. Down regulation of this epitranscriptomic regulator has been found to inhibit cancer progression. Silencing the methyltransferase activity of METTL3 is a lucrative strategy to design anticancer drugs. In this study 3600 commercially available molecules were screened against METTL3 using brute force screening approach. However, none of these compounds take advantage of the unique Y-shaped binding cavity of the protein, raising the need for de novo drug designing strategies. As such, 125 branched, Y-shaped molecules were designed by \"stitching\" together the chemical fragments of the best inhibitors that interact strongly with the METTL3 binding pocket. This results in molecules that have the three-dimensional structure and functional groups which enable it to fit in the METTL3 cavity like fingers in a glove, having unprecedented selectivity and binding affinities. The designed compounds were further refined based on Lipinski's rule, docking score and synthetic accessibility. The molecules faring well in these criteria were simulated for 100 ns to check the stability of the protein inhibitor complex followed by binding free energy calculation.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1038-1051"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803813","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 studies on <i>Bacillus subtilis</i> RbgA: insights into the RbgA-ribosome association and GTPase activity.","authors":"Upendra N, Kavya K M, Krishnaveni S","doi":"10.1080/07391102.2024.2444412","DOIUrl":"https://doi.org/10.1080/07391102.2024.2444412","url":null,"abstract":"<p><p>RbgA (ribosome biogenesis GTPase A) is involved in the maturation of later stages of the 50S ribosomal subunit by associating with the 45S ribosomal subunit. However, this binding relies on the specific nucleotide-bound state of RbgA-GTP-bound state is more favorable compared GDP-bound state, attributed to the conformational variations between those states. Therefore, to explore the conformational changes of RbgA, all-atom MD simulations of <i>Bs</i>RbgA were carried out under various nucleotide bound states (GDP, GTP, GTP-Mg²⁺ and GMPPNP-Mg²⁺). The analysis of overall conformational changes using RMSD and Rg revealed sharp equilibration for GTP-Mg²⁺ and GMPPNP-Mg²⁺ nucleotide bound systems. Investigating internal variations through RMSF and cluster analyses helps us to identify the functionally important regions and nucleotide driven conformational variations that may stabilize/destabilize the RbgA-ribosome association. In addition, the construction and analyses of the dynamical protein contact network from the simulated trajectory reveal the nucleotide dependent allosteric connections between the nucleotide binding site and the rRNA interacting residues. Furthermore, the visualization followed by the dynamical distance calculations exhibited the possible role of Mg²⁺ in assisting GTP hydrolysis, such as (i) positioning the Asp150 of the switch-I (Sw-I) loop residue in a catalytically feasible configuration and (ii) stabilizing the solvated water molecules at the active-site through Mg²⁺ coordination. The results of our study can be used to design better chemical agents to regulate ribosome biogenesis through modulation of the function of the RbgA.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-11"},"PeriodicalIF":2.7,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931864","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":"The anti-MRSA resource: a comprehensive archive of anti-MRSA peptides and essential oils.","authors":"Rajat Kumar Mondal, Ananya Anurag Anand, Debarup Sen, Sintu Kumar Samanta","doi":"10.1080/07391102.2024.2446670","DOIUrl":"https://doi.org/10.1080/07391102.2024.2446670","url":null,"abstract":"<p><p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), a major cause of fatalities due to Antimicrobial Resistance (AMR), can act as an opportunistic pathogen despite being part of the normal human flora. MRSA infections, such as skin infections, pneumonia, sepsis, and surgical site infections, have risen significantly, with bloodstream infection cases increasing from 21% in 2016 to 35% in 2020. This surge has prompted research into alternative treatments like nanomaterials, photodynamic therapy, antimicrobial peptides (AMPs), and essential oils (EOs). AMPs and EOs have shown higher success rates compared to other alternatives, gaining significant attention for their effectiveness against MRSA. In this perspective, we have created a database for peptides and EOs that have been discovered to treat MRSA. Manual data curation was done to get related information on each of the anti-MRSA EOs and AMPs from the PubMed articles. This led to the curation of 1789 peptides (1029 unique) and 863 EOs (671 unique) that have been reported against MRSA. This was followed by database creation and the development of tools for sequence analysis and determination of physiochemical properties. This resource has been named 'The Anti-MRSA Resource' or 'TAMRSAR' which we believe will aid in future drug development efforts to combat the diseases caused by MRSA. The database is accessible on any web browser at the URL: https://bblserver.org.in/tamrsar/.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931947","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":"Conformational dynamics of the membrane protein of MERS-CoV in comparison with SARS-CoV-2 in ERGIC complex.","authors":"Subha Yegnaswamy, Selvaa Kumar C, Ebtisam Aldaais","doi":"10.1080/07391102.2024.2437529","DOIUrl":"https://doi.org/10.1080/07391102.2024.2437529","url":null,"abstract":"<p><p>The present study explores the conformational dynamics of the membrane protein of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) within the Endoplasmic Reticulum-Golgi Intermediate Compartment (ERGIC) complex using an all-atomistic molecular dynamics simulation approach. Significant structural changes were observed in the N-terminal, C-terminal, transmembrane, and beta-sheet sandwich domains of the MERS-CoV membrane protein. This study also highlights the structural similarities between the MERS-CoV and the SARS-CoV-2 membrane proteins, particularly in how both exhibit a distinct kink in the transmembrane helix caused by aromatic residue-lipid interactions. A structural expansion below the transmembrane and above the beta-sheet sandwich domain within the dimer was observed in all the M-proteins. This site on the beta-sheet sandwich domains near the C-terminal end could serve as a potential drug-binding site. Notably, a stable helical structure was identified in the C-terminal domain of the MERS-CoV membrane protein, whereas a proper secondary structural conformation was not observed in the SARS-CoV-2 membrane protein. Further, the SARS-CoV-2 membrane protein exhibited stronger binding to the lipid bilayer than the MERS-CoV, indicating its greater structural stability within the ERGIC complex. The structural similarity between the membrane protein of MERS-CoV and SARS-CoV-2 suggests the feasibility of employing a common inhibitor against these beta-coronaviruses. Furthermore, this analysis enhances our understanding of the membrane protein's interactions with proteins and lipids, paving the way for therapeutic developments against these viruses.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binding ability of Delta and Omicron towards the angiotensin-converting enzyme 2 receptor and antibodies: a computational study.","authors":"Quoc-Thai Nguyen, Tan Thanh Mai, Lam-Truong Tuong, Thi-Thao-Nhung Nguyen, Thanh-Phuong Vo, Dac-Nhan Nguyen, Cong-Thanh Phan-Van, Dieu-Thuong Thi Trinh, Van-Thanh Tran, Khac-Minh Thai","doi":"10.1080/07391102.2024.2446659","DOIUrl":"https://doi.org/10.1080/07391102.2024.2446659","url":null,"abstract":"<p><p>The COVID-19 pandemic posed a threat to global society. Delta and Omicron are concerning variants due to the risk of increasing human-to-human transmissibility and immune evasion. This study aims to evaluate the binding ability of these variants toward the angiotensin-converting enzyme 2 receptor and antibodies using a computational approach. The receptor-binding domain (RBD) of the two variants was created by CHARMM-GUI and then docked to the hACE2 receptor and two antibodies (REGN10933 and REGN10987). These complexes were also subjected to molecular dynamics simulation within 100 ns. As a result, the two variants, Omicron and Delta, exhibited stronger interaction with the hACE2 receptor than the wild type. The mutations in the RBD region also facilitated the virus's escape from antibody neutralization.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931930","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":"Organotin(IV) derivatives of 4-chloro-2-methylphenoxyacetic acid: synthesis, spectral characterization, X-ray structures, anticancer, enzyme inhibition, antileishmanial, antimicrobial and antioxidant activities.","authors":"Shahnaz Rahim, Abdul Sadiq, Aneela Javed, Niaz Muhammad, Mohammed Rafi Shaik, Mohamed E Assal, Maciej Kubicki, Khurshid Ayub, Nighat Fatima, Ali Haider, Sabahat Habib, Sehrish Sarfaraz, Saqib Ali","doi":"10.1080/07391102.2024.2438362","DOIUrl":"https://doi.org/10.1080/07391102.2024.2438362","url":null,"abstract":"<p><p>Four organotin(IV) carboxylate complexes; (C₄H₉)₃SnL (<b>1</b>), CH₃SnL (<b>2</b>), (C₄H₉)₂SnL₂ (<b>3</b>) and (CH₃)₂SnL₂ (<b>4</b>) are synthesized by the condensation reaction of organotin(IV) chlorides with sodium-4-chloro-2-methylphenoxyacetate (<b>NaL</b>). The FT-IR spectra suggested bridging/chelating bidentate coordination of the ligand to the tin atom. Single-crystal XRD analysis authenticated the FT-IR findings for <b>1</b> and <b>2</b>. The NMR study has shown no significant differences in the signals of the free and coordinated ligand except for absence of a proton and up-filed/down-field shift of the C signal of the carboxyl group in the spectra. Complexes <b>1</b>-<b>4</b> have shown better enzyme inhibition, antioxidant, antimicrobial, and anticancer activities compared to the free ligand acid. Complex <b>3</b> was the most active inhibitor of AChE, BChE, α-glucosidase and α-amylase with IC₅₀ values of 43.76, 102.39, 232.71 and 91.84 µg/mL, respectively. Additionally, <b>3</b> with IC₅₀ values of 7.52 and 8.77 µg/mL in the DPPH and ABTS assays, respectively was better antioxidant than the standard. Complex <b>4</b> was the most efficient inhibitor of MAO-B and COX-2 enzymes with IC₅₀ values of 106.99 and 12.98 µg/mL, respectively, while <b>1</b> (IC₅₀ = 38.97 µg/mL) has shown the highest 5-LOX inhibition potential. Complexes <b>1</b>-<b>4</b> with IC₅₀ values in the range 237.51-168.35 µg/mL have shown better antileishmanial activity than <b>HL</b> (IC₅₀ = 277.57 µg/mL). The compounds showed good to potent antiproliferative activity in malignant glioma U87 cells with IC₅₀ values in the range 12.54 ± 0.05 to 37.65 ± 0.04 µg/mL. Antimicrobial activities have shown promising results for the compounds compared to the standards in some cases.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921319","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":"Virtual screening of targeted acrylamide warheads for identification of covalent inhibitors of Cryptopain, a cysteine protease of <i>Cryptosporidium parvum</i>.","authors":"Misgana Mengistu Asmare, Ajit Kumar Dhal, Rajani Kanta Mahapatra, Soon-Il Yun","doi":"10.1080/07391102.2024.2446664","DOIUrl":"https://doi.org/10.1080/07391102.2024.2446664","url":null,"abstract":"<p><p>Cryptosporidiosis is an infection induced by the single-celled protozoan Cryptosporidium parasite. This parasite commonly infects the intestines of humans and animals, leading to gastrointestinal symptoms such as diarrhea, stomach cramps, nausea, and vomiting. Cryptopain protein, a type of cysteine protease found in the genome of <i>Cryptosporidium parvum</i> plays an important role in cell invasion and its survival. In this study, we mainly focused on the structural validation and reliability of docking aspects of the Cryptopain protein of <i>C. parvum</i>. The best-modeled structure of Cryptopain protein was run in a water environment through a 200 ns Molecular Dynamics (MD) simulation study. We employed a covalent docking scheme to screen suitable inhibitors against our target protein. Furthermore, the reliability of the binding mode for the best possible inhibitors was validated at a 100 ns time frame through a complex MD simulation study. From docking and simulation studies, we found Z3952175270 as a possible inhibitor on the basis of docking score and binding affinity for the possible binding site in the Cryptopain protein. Our findings highlight the potential of targeting Cryptopain protein with specific inhibitors, which could pave the way for the development of novel therapeutic strategies against cryptosporidiosis. This work contributes to the field by providing a deeper understanding of the molecular interactions involved in Cryptopain inhibition, potentially leading to effective treatments for a disease that significantly impacts public health, particularly in immunocompromised individuals and in areas with limited access to clean water.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921388","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}