Journal of Biomolecular Structure & Dynamics最新文献

{"title":"<i>In silico</i> exploration and <i>in vitro</i> validation of the filarial thioredoxin reductase inhibitory activity of Scytonemin and its derivatives.","authors":"Animesh Sen, Varun Dewaker, Utsab Debnath, Kuladip Jana, Jnanendra Rath, Nikhilesh Joardar, Santi P Sinha Babu","doi":"10.1080/07391102.2023.2283876","DOIUrl":"10.1080/07391102.2023.2283876","url":null,"abstract":"<p><p>Lymphatic filariasis (LF) caused by the vector borne parasitic nematode <i>Wuchereria bancrofti</i> is of major concern of the World Health Organization (WHO). Lack of potential drug candidates worsens the situation. Presently available drugs are promising in killing the microfilaria (mf) but are not effective as adulticidal therapeutics. Previous studies have revealed that routine administration of the available drugs (albendazole, ivermectin and albendazole) sometime is associated with severe adverse effects (SAEs) in co-infection state. Therefore, potential and safe therapeutics are still required. Earlier studies on filarial thioredoxin reductase (TrxR) have shown that successful inhibition of it can lead to apoptotic death of the parasites. TrxR in filarial parasites plays a significant role in disease progression and pathogenesis, hence efficient non-reversible inhibition of TrxR can be a good strategy to treat LF. In this research, inhibitory potential of Scytonemin, a cyanobacterial metabolite on filarial TrxR was evaluated <i>via</i> different <i>in silico</i> methods and validated through <i>in vitro</i> experiments. Parasite death upon exposure to Scytonemin can be correlated with the TrxR inhibiting capacity of the compound. Therefore, this cyanobacterial-derived compound may possibly be used further as novel and safe therapeutic candidate against filarial infection.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"890-902"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291012","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 potential of <i>Halalkalibacterium halodurans</i> laccase for endosulfan and chlorophacinone degradation: insights from molecular docking and molecular dynamics simulations.","authors":"Rajat Pant, Ravi Kumar, Shilpa Sharma, Ramanathan Karuppasamy, Shanthi Veerappapillai","doi":"10.1080/07391102.2023.2283165","DOIUrl":"10.1080/07391102.2023.2283165","url":null,"abstract":"<p><p>Pesticides are widely used in agriculture but at the same time, a majority of them are known to cause serious harm to health and the environment. In the recent past, laccases have been reported as key enzymes having the ability to degrade pollutants by converting them into less toxic forms. In this investigation, laccase from polyextremophilic bacterium <i>Halalkalibacterium halodurans</i> C-125 was analyzed for its structural, physicochemical, and functional characterization using in <i>silico</i> approaches. The 3D model of the said enzyme is unknown; therefore, the model was generated by template-independent modeling using ROBETTA, I-TASSER, and Alphafold server. The best-generated model from Alphafold with a confidence of 0.95 was validated from ERRAT and Verify 3D scores of 89.95 and 91.80%, respectively. The Ramachandran plot generated using the PROCHECK server further predicted the accuracy of the model with 93.7% and 5.9% of residues present in most favored and additional allowed regions of the plot respectively. The active sites, ion binding sites, and subcellular localization of laccase were also predicted. The generated model was docked with 121 pollutants (pesticides, insecticides, herbicides, fungicides, and rodenticides) for its degradation potential towards these pollutants. Two ligands chlorophacinone (based on the highest binding energy) and endosulfan (based on agricultural uses) were selected for molecular dynamic simulation studies. Endosulfan as a pesticide is banned but in some countries governments allow its use for special purposes which need serious consideration on developing bioremediation approaches for endosulfan degradation. MD simulation studies revealed that both chlorophacinone and endosulfan form hydrogen bonds and hydrophobic bonds with the active site of laccase and chlorophacinone-laccase complex were more stable in comparison to endosulfan. The present investigation provides insight into the structural features of laccase and its potential for the degradation of pesticides which can be further validated by experimental data.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"742-756"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291025","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 dynamics of <i>Escherichia coli</i> FtsZ dimer.","authors":"Vidyalakshmi C Muthukumar","doi":"10.1080/07391102.2023.2287486","DOIUrl":"10.1080/07391102.2023.2287486","url":null,"abstract":"<p><p>The <i>E. coli</i> FtsZ dimer was studied to gain insights into FtsZ protofilament formation. In the simulation study of the <i>M. janaschii</i> dimer it was found that the monomer-monomer contacts in the GDP bound dimer is lower which results in the high curvature of the GDP bound protofilaments. In this study, the <i>E. coli</i> FtsZ dimer was simulated. The initial structure was obtained from our previous study in which we had simulated the <i>E. coli</i> FtsZ monomer with its C-terminal IDR (Intrinsically Disordered Region). The <i>M. janaschii</i> FtsZ dimer subunit contacts were used as the starting configuration. Simulations of the dimer were performed with GTP and with GDP. It is found that the central helix H5 closes by about 15 degrees in the simulation with GTP than in the simulation with GDP. The C-terminal IDR and the C-terminal domain region between SC2 and HC2 are found to have much high flexibility and hence exhibit domain motion.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"903-916"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444820","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":"Structural and molecular investigation of the impact of S30L and D88N substitutions in G9R protein on coupling with E4R from Monkeypox virus (MPXV).","authors":"Yifan Jin, Syed Jawad Asad Gillani, Farah Batool, Fahad M Alshabrmi, Eid A Alatawi, Yasir Waheed, Anwar Mohammad, Abbas Khan, Dong-Qing Wei","doi":"10.1080/07391102.2023.2291159","DOIUrl":"10.1080/07391102.2023.2291159","url":null,"abstract":"<p><p>Understanding the pathogenesis mechanism of the Monkeypox virus (MPXV) is essential to guide therapeutic development against the Monkeypox virus. In the current study, we investigated the impact of the only two reported substitutions, S30L, D88N, and S30L-D88N on the G9R of the replication complex in 2022 with E4R using structural modeling, simulation, and free energy calculation methods. From the molecular docking and dissociation constant (K_D) results, it was observed that the binding affinity did not increase in the mutants, but the interaction paradigm was altered by these substitutions. Molecular simulation data revealed that these mutations are responsible for destabilization, changes in protein packing, and internal residue fluctuations, which can cause functional variance. Additionally, hydrogen bonding analysis revealed that the estimated number of hydrogen bonds are almost equal among the wild-type G9R and each mutant. The total binding free energy for the wild-type G9R with E4R was -85.00 kcal/mol while for the mutants the TBE was -42.75 kcal/mol, -43.68 kcal/mol, and -48.65 kcal/mol respectively. This shows that there is no direct impact of these two reported mutations on the binding with E4R, or it may affect the whole replication complex or any other mechanism involved in pathogenesis. To explore these variations further, we conducted PCA and FEL analyses. Based on our findings, we speculate that within the context of interaction with E4R, the mutations in the G9R protein might be benign, potentially leading to functional diversity associated with other proteins.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1015-1026"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087025","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":"Inhibition potential of natural flavonoids against selected omicron (B.1.19) mutations in the spike receptor binding domain of SARS-CoV-2: a molecular modeling approach.","authors":"Anuj Kumar, Mansi Dutt, Budheswar Dehury, Gustavo Sganzerla Martinez, Cynthia L Swan, Alyson A Kelvin, Christopher D Richardson, David J Kelvin","doi":"10.1080/07391102.2023.2291165","DOIUrl":"10.1080/07391102.2023.2291165","url":null,"abstract":"<p><p>The omicron (B.1.19) variant of contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is considered a variant of concern (VOC) due to its increased transmissibility and highly infectious nature. The spike receptor-binding domain (RBD) is a hotspot of mutations and is regarded as a prominent target for screening drug candidates owing to its crucial role in viral entry and immune evasion. To date, no effective therapy or antivirals have been reported; therefore, there is an urgent need for rapid screening of antivirals. An extensive molecular modelling study has been performed with the primary goal to assess the inhibition potential of natural flavonoids as inhibitors against RBD from a manually curated library. Out of 40 natural flavonoids, five natural flavonoids, namely tomentin A (-8.7 kcal/mol), tomentin C (-8.6 kcal/mol), hyperoside (-8.4 kcal/mol), catechin gallate (-8.3 kcal/mol), and corylifol A (-8.2 kcal/mol), have been considered as the top-ranked compounds based on their binding affinity and molecular interaction profiling. The state-of-the-art molecular dynamics (MD) simulations of these top-ranked compounds in complex with RBD exhibited stable dynamics and structural compactness patterns on 200 nanoseconds. Additionally, complexes of these molecules demonstrated favorable free binding energies and affirmed the docking and simulation results. Moreover, the post-simulation validation of these interacted flavonoids using principal component analysis (PCA) revealed stable interaction patterns with RBD. The integrated results suggest that tomentin A, tomentin C, hyperoside, catechin gallate, and corylifol A might be effective against the emerging variants of SARS-CoV-2 and should be further evaluated using <i>in-vitro</i> and <i>in-vivo</i> experiments.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1068-1082"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803844","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":"Network pharmacology and molecular docking to study the potential molecular mechanism of Qi Fu Yin for diabetic encephalopathy.","authors":"Xiaodi Guo, Feiyan Wang, Meiling Zheng, Liang Li, Long Li, Jin Wang, Shan Miao, Shanbo Ma, Xiaopeng Shi","doi":"10.1080/07391102.2023.2289038","DOIUrl":"10.1080/07391102.2023.2289038","url":null,"abstract":"<p><p>Diabetic encephalopathy is a chronic complication of diabetes that lacks an optimized treatment strategy. The present study sought to elucidate the potential molecular mechanism of Qi Fu Yin in improving diabetic encephalopathy through network pharmacology. The active components and target information of Qi Fu Yin were obtained from the TCMSP and Swiss target databases, while the target information of diabetic encephalopathy was sourced from Gene cards, OMIM, and Pharm Gkb databases. Enrichment analyses of KEGG and GO were conducted utilizing drug-disease common targets, while protein-protein interactions were predicted through the utilization of the STRING database platform. Subsequently, molecular docking was executed via Auto Dock Vina to authenticate the interaction between core components and core targets. The findings revealed that Qi Fu Yin exhibited 178 common targets with diabetic encephalopathy, and the enrichment analyses demonstrated that these targets were associated with lipid and atherosclerosis, AGE-RAGE signaling pathways, and other related pathways. The findings of the molecular docking indicated a favorable binding affinity between the active components of drug and the core targets, with EGF and quercetin exhibiting the most notable docking score. Additionally, the molecular dynamics simulation corroborated this high affinity. These results suggested that the active ingredients of Qi Fu Yin, including quercetin and kaempferol, may modulated the expression of genes such as IL10, TNF, EGF, and MMP2, thereby activating the AGE-RAGE signaling pathways and potentially serving as a therapeutic intervention for diabetic encephalopathy.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"917-931"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138477830","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 anti-hyperglycemic compounds in <i>Cordyceps militaris</i> ethyl acetate extract: <i>in vitro</i> and <i>in silico</i> studies.","authors":"Thanh Q Bui, Ton That Huu Dat, Phan Tu Quy, Nguyen Thi Thanh Hai, Nguyen Minh Thai, Nguyen Vinh Phu, Le Van Tuan, Lam K Huynh, Mai Suan Li, Nguyen Thi Ai Nhung","doi":"10.1080/07391102.2023.2283156","DOIUrl":"10.1080/07391102.2023.2283156","url":null,"abstract":"<p><p><i>Cordyceps militaris</i> has been long known for valuable health benefits by folk experience and was recently reported with diabetes-tackling evidences, thus deserving extending efforts on screening for component-activity relationship. In this study, experiments were carried out to find the evidence, justification, and input for computations on the potential against diabetes-related protein structures: PDB-4W93, PDB-3W37, and PDB-4A3A. Liquid chromatography identified 14 bioactive compounds in the ethyl acetate extract (<b>1</b>-<b>14</b>) and quantified the contents of cordycepin (0.11%) and adenosine (0.01%). Bioassays revealed the overall potential of the extract against <i>α</i>-amylase (IC₅₀ = 6.443 ± 0.364 mg.mL^-1) and <i>α</i>-glucosidase (IC₅₀ = 2.580 ± 0.194 mg.mL^-1). A combination of different computational platforms was used to select the most promising candidates for applications as anti-diabetic bio-inhibitors, i.e. <b>1</b> (ground state: -888.49715 a.u.; dipole moment 3.779 Debye; <math><mrow><mrow><mrow><mover><mrow><mtext>DS</mtext></mrow><mo>¯</mo></mover></mrow></mrow></mrow></math> -12.3 kcal.mol^-1; polarizability 34.7 ų; log<i>P</i> - 1.30), <b>10</b> (ground state: -688.52406 a.u.; dipole moment 5.487 Debye; <math><mrow><mrow><mrow><mover><mrow><mtext>DS</mtext></mrow><mo>¯</mo></mover></mrow></mrow></mrow></math> -12.6 kcal.mol^-1; polarizability 24.9 ų; log<i>P</i> - 3.39), and <b>12</b> (ground state: -1460.07276 a.u.; dipole moment 3.976 Debye; <math><mrow><mrow><mrow><mover><mrow><mtext>DS</mtext></mrow><mo>¯</mo></mover></mrow></mrow></mrow></math> -12.5 kcal.mol^-1; polarizability 52.4 ų; log<i>P</i> - 4.39). The results encourage further experimental tests on cordycepin (<b>1</b>), mannitol (<b>10</b>), and adenosylribose (<b>12</b>) to validate their in-practice diabetes-related activities, thus conducive to hypoglycemic applications.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"627-643"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299175","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":"Accelerated molecular dynamics study to compare the thermostability of <i>Bacillus licheniformis</i> and <i>Aspergillus niger</i> α-amylase.","authors":"Umi Baroroh, Nindi Salma Chantika, Ade R R Firdaus, Taufik Ramdani Tohari, Toto Subroto, Safri Ishmayana, Agus Safari, Saadah Diana Rachman, Muhammad Yusuf","doi":"10.1080/07391102.2023.2283152","DOIUrl":"10.1080/07391102.2023.2283152","url":null,"abstract":"<p><p>The thermostability of enzymes plays a significant role in the starch hydrolysis process in the industry. The structural difference between thermostable <i>Bacillus licheniformis</i> α-amylase (BLA) and thermolabile <i>Aspergillus niger</i> α-amylase (ANA) is interesting to be explored. This work aimed to study the thermostability-determining factor of BLA as compared to a non-thermostable enzyme, ANA, using molecular dynamics (MD) simulation at a high temperature. A 100 ns of classical MD, which was followed by 200 ns accelerated MD was conducted to explore the conformational changes of the enzyme. It is revealed that the intramolecular interactions through salt bridge interactions and the presence of calcium ions dominates the stability effect of BLA, despite the absence of a disulfide bond in the structure. These results should be useful in designing a thermostable enzyme that can be used in industrial processes.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"571-581"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138047044","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":"Albumin from sera of rheumatoid arthritis patients share multiple biochemical, biophysical and immunological properties with <i>in vitro</i> generated glyco-nitro-oxidized-albumin.","authors":"Akhlas Tarannum, Zarina Arif, Mohd Mustafa, Khursheed Alam, Moinuddin, Safia Habib","doi":"10.1080/07391102.2023.2283153","DOIUrl":"10.1080/07391102.2023.2283153","url":null,"abstract":"<p><p>The purpose of the present study is to explore the effects of endogenous stressors on structure and function of rheumatoid arthritis (RA) patients' albumin. In contrast to glycated-albumin or nitro-oxidized-albumin, high titre antibodies against glyco-nitro-oxidized-albumin were found in the sera of RA patients. Also, compared to the other two modified forms of albumin, glyco-nitro-oxidized-albumin showed highest percent inhibition. Albumin isolated from RA patients' sera displayed hyperchromicity and quenching of tyrosine and tryptophan fluorescence. Fluorescence spectroscopy studies also revealed the presence of dityrosine and advanced glycation end products in RA patient's albumin. RA patients' albumin showed weaker binding with 1-anilinonaphthalene-8-sulfonic acid dye. Secondary structure alterations were demonstrated by circular dichroism and Fourier transform infrared spectroscopy. Biochemical investigations revealed substantial decline in the availability of free side chains of amino acid residues; increased carbonyls and decreased sulfhydryls in RA patients' albumin. The functional impairment in RA patients' albumin was revealed by their low binding with bilirubin and cobalt. Liquid chromatography mass spectrometry analysis revealed the presence of N^ε-(carboxymethyl) lysine and 3-nitrotyrosine in RA patients' albumin. The amyloidogenic aggregation of RA patients' albumin was confirmed by Congo red absorption and thioflavin-T fluorescence assays. The morphology of the aggregates was visualized under scanning and transmission electron microscope. From the above findings, we inferred that endogenous stress in RA patients have modified albumin and produce structural/functional abnormalities. Also, the presence of anti-glyco-nitro-oxidized-albumin antibodies along with other clinical features may be used as biomarker for the diagnosis and assessment of treatment responses in RA patients.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"582-598"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138047045","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":"Structural insights into ACE2 interactions and immune activation of SARS-CoV-2 and its variants: an <i>in-silico</i> study.","authors":"Sarina Yousefbeigi, Farah Marsusi","doi":"10.1080/07391102.2023.2283158","DOIUrl":"10.1080/07391102.2023.2283158","url":null,"abstract":"<p><p>The initial interaction between COVID-19 and the human body involves the receptor-binding domain (RBD) of the viral spike protein with the angiotensin-converting enzyme 2 (ACE2) receptor. Likewise, the spike protein can engage with immune-related proteins, such as toll-like receptors (TLRs) and pulmonary surfactant proteins A (SP-A) and D (SP-D), thereby triggering immune responses. In this study, we utilize computational methods to investigate the interactions between the spike protein and TLRs (specifically TLR2 and TLR4), as well as (SP-A) and (SP-D). The study is conducted on four variants of concern (VOC) to differentiate and identify common virus behaviours. An assessment of the structural stability of various variants indicates slight changes attributed to mutations, yet overall structural integrity remains preserved. Our findings reveal the spike protein's ability to bind with TLR4 and TLR2, prompting immune activation. In addition, our <i>in-silico</i> results reveal almost similar docking scores and therefore affinity for both ACE2-spike and TLR4-spike complexes. We demonstrate that even minor changes due to mutations in all variants, surfactant A and D proteins can function as inhibitors against the spike in all variants, hindering the ACE2-RBD interaction.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"665-678"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138047050","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}