Journal of Biomolecular Structure & Dynamics最新文献

{"title":"A computational strategy for systematic virtual screening of plasmodium falciparum heme detoxification protein inhibitors from the Drugbank database.","authors":"Shrikant Nema, Rini Chaturvedi, Kanika Verma, Anup R Anvikar, Archana Tiwari, Praveen Kumar Bharti","doi":"10.1080/07391102.2023.2301510","DOIUrl":"10.1080/07391102.2023.2301510","url":null,"abstract":"<p><p>Antimalarial drug resistance poses one of the greatest threats to malaria treatment, resulting in increased morbidity and mortality. Heme Detoxification Protein (HDP) is among the essential hemoglobinases of P. falciparum (Pf), a vital molecular target for the treatment of malaria. In this study, we utilized the virtual screening workflow tool of the Schrodinger suite to find the best hits for the PfHDP from the DrugBank library. A total of 14,942 compounds were identified against the PfHDP. The top compounds with the highest docking scores and least energy scores were subjected to molecular simulations for 500 nanosecond to check the stability of the protein-drug complexes. The top three DrugBank compounds were found to be stable over 500 ns, namely DB09298 (silibinin), DB07426 (1-Hydroxy-2-(1,1':3',1''-Terphenyl-3-Yloxy) Ethane-1,1-Diyl] Bis (Phosphonic Acid), and DB07410 [(2-(3-Dibenzofuran-4-yl-Phenyl)-1-Hydroxy-1-Phosphono-Ethyl]-Phosphonic Acid). Overall analysis suggests that the top three compounds, DB09298, DB07426, and DB07410, have good stability for 500 ns. Their scaffolds can be used to design and develop new analogs of the target HDP protein. Silibinin, the anti-cancer drug, was found to be highly stable for the entire simulation period as compared to the other compounds. DB07426 shows its therapeutic effect on bones, especially in the treatment of osteoporosis, and DB07410 has anti-tumor, antibacterial, anti-oxidative, and anti-viral activities. All three compounds can be considered for repurposing as antimalarial drugs to evaluate the binding capacity or inhibition potential of these compounds. Further in-vivo and in-vitro analysis against the PfHDP protein should be conducted.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3156-3171"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403024","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 comprehensive bioinformatics analysis identifies mitophagy biomarkers and potential Molecular mechanisms in hypertensive nephropathy.","authors":"Jiayou Liu, Luda Feng, Qi Jia, Jia Meng, Yun Zhao, Lei Ren, Ziming Yan, Manrui Wang, Jianguo Qin","doi":"10.1080/07391102.2024.2311344","DOIUrl":"10.1080/07391102.2024.2311344","url":null,"abstract":"<p><p>Mitophagy, the selective removal of damaged mitochondria, plays a critical role in kidney diseases, but its involvement in hypertensive nephropathy (HTN) is not well understood. To address this gap, we investigated mitophagy-related genes in HTN, identifying potential biomarkers for diagnosis and treatment. Transcriptome datasets from the Gene Expression Omnibus database were analyzed, resulting in the identification of seven mitophagy related differentially expressed genes (MR-DEGs), namely PINK1, ULK1, SQSTM1, ATG5, ATG12, MFN2, and UBA52. Further, we explored the correlation between MR-DEGs, immune cells, and inflammatory factors. The identified genes demonstrated a strong correlation with Mast cells, T-cells, TGFβ3, IL13, and CSF3. Machine learning techniques were employed to screen important genes, construct diagnostic models, and evaluate their accuracy. Consensus clustering divided the HTN patients into two mitophagy subgroups, with Subgroup 2 showing higher levels of immune cell infiltration and inflammatory factors. The functions of their proteins primarily involve complement, coagulation, lipids, and vascular smooth muscle contraction. Single-cell RNA sequencing revealed that mitophagy was most significant in proximal tubule cells (PTC) in HTN patients. Pseudotime analysis of PTC confirmed the expression changes observed in the transcriptome. Intercellular communication analysis suggested that mitophagy might regulate PTC's participation in intercellular crosstalk. Notably, specific transcription factors such as HNF4A, PPARA, and STAT3 showed strong correlations with mitophagy-related genes in PTC, indicating their potential role in modulating PTC function and influencing the onset and progression of HTN. This study offers a comprehensive analysis of mitophagy in HTN, enhancing our understanding of the pathogenesis, diagnosis, and treatment of HTN.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3204-3223"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706888","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 computational investigation of potential plant-based bioactive compounds against drug-resistant <i>Staphylococcus aureus</i> of multiple target proteins.","authors":"Sarit Prabha, Pallavi Chauhan, Sudeesh Warkare, Khushhali M Pandey","doi":"10.1080/07391102.2023.2297009","DOIUrl":"10.1080/07391102.2023.2297009","url":null,"abstract":"<p><p>Drug-resistant <i>Staphylococcus aureus</i> (DRSA) poses a significant global health threat, like bacteremia, endocarditis, skin, soft tissue, bone, and joint infections. Nowadays, the resistance against conventional drugs has been a prompt and focused medical concern. The present study aimed to explore the inhibitory potential of plant-based bioactive compounds (PBBCs) against effective target proteins using a computational approach. We retrieved and verified 22 target proteins associated with DRSA and conducted a screening process that involved testing 87 PBBCs. Molecular docking was performed between screened PBBCs and reference drugs with selected target proteins via AutoDock. Subsequently, we filtered the target proteins and top PBBCs based on their binding affinity scores. Furthermore, molecular dynamic simulation was carried out through GROMACS for a duration of 100 ns, and the binding free energy was calculated using the gmx_MMPBSA. The result showed consistent hydrogen bonding interactions among the amino acid residues Ser 149, Arg 151, Thr 165, Thr 216, Glu 239, Ser 240, Ile 14, as well as Asn 18, Gln 19, Lys 45, Thr 46, Tyr 109, with their respective target proteins of the penicillin-binding protein and dihydrofolate reductase complex. Additionally, we assessed the pharmacokinetic properties of screened PBBCs <i>via</i> SwissADME and AdmetSAR. The findings suggest that β-amyrin, oleanolic acid, kaempferol, quercetin, and friedelin have the potential to inhibit the selected target proteins. In future research, both <i>in vitro</i> and <i>in vivo</i>, experiments will be needed to establish these PBBCs as potent antimicrobial drugs for DRSA.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3311-3329"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138885086","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":"In silico and in vitro evaluation of newly synthesized pyrazolo-pyridine fused tetrazolo-pyrimidines derivatives as potential anticancer and antimicrobial agents.","authors":"Harsh C Patel, Manan S Patel, Jaydeepkumar N Parekh, Dipakkumar D Chudasama, Priyanka Dalwadi, Anju Kunjadiya, Vaibhav Bhatt, Krunal M Modi, Chirag N Patel, Kesur R Ram","doi":"10.1080/07391102.2023.2298731","DOIUrl":"10.1080/07391102.2023.2298731","url":null,"abstract":"<p><p>Diversely functionalized pyrazolo-pyridine fused tetrazolo-pyrimidines <b>10aa-am</b> and <b>10ba-bn</b> were successfully synthesized <i>via</i> a catalyst-free synthetic protocol with moderate to very good yields. The compounds were evaluated for cytotoxicity against MCF-7 and HEK-293 cells using MTT assay. Among the tested compounds, <b>10ab</b> (IC₅₀- 23.83 µM) and <b>10ah</b> (IC₅₀- 23.30 µM) demonstrated the highest potency against MCF-7 cells, while <b>10bc</b> (IC₅₀- 14.46 µM) and <b>10bh</b> (IC₅₀- 2.53 µM) exhibited excellent cytotoxicity against HEK-293 cells. Additionally, antibacterial screening was performed against three Gram-negative bacteria (<i>E. coli, P. aeruginosa,</i> and <i>S. enterica</i>) and three Gram-positive bacteria (<i>S. aureus, B. megaterium, and B. subtilis</i>) using broth dilution method, while antifungal activity was assessed against three fungal strains (<i>A. niger, Penicillium, and S. cerevisiae</i>) using agar well diffusion method. In antimicrobial screening, the majority of the compounds demonstrated significant antibacterial efficacy compared to antifungal activity. We also conducted comprehensive computational studies, including DFT calculations, molecular docking and dynamics, and drug-likeness assessments. In the DFT study, compounds <b>10ac</b> and <b>10bc</b> displayed stable conformations, indicating their potential for higher therapeutic activity. Molecular docking analyses revealed compelling interactions, with compound <b>10ah</b> demonstrating docking score -7.42 kcal/mol against catalytical domain PARP1 (PDB ID: 7KK4) and <b>10bh</b> exhibiting a best docking score -10.77 kcal/mol against human corticotropin-releasing factor receptor 1 (PDB ID: 4Z9G). A 100 ns molecular dynamics (MD) simulation study of compounds <b>10ah</b> and <b>10bh</b> revealed the stable conformation and binding energy in a stimulating environment. In drug-likeness assessments, both the compounds <b>10ah</b> and <b>10bh</b> adhere all the established guidelines.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3467-3490"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037741","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 and stability analysis of potential ADP-ribose modification sites on vascular endothelial growth factor (VEGF) through molecular dynamics simulation.","authors":"Kalayakkattil Sreelakshmi, Kadabagere Narayanaswamy Hemavathi, Rajesh Raju, Kumar V B Sameer, Thottethodi Subramanya Keshava Prasad, Perumana R Sudhakaran, Chandran S Abhinand","doi":"10.1080/07391102.2023.2297821","DOIUrl":"10.1080/07391102.2023.2297821","url":null,"abstract":"<p><p>Post-translational modifications (PTMs) are crucial covalent processes that alter protein properties, achieved through proteolytic cleavage or addition of modifying groups like acetyl, phosphoryl, glycosyl, or methyl to amino acids. ADP-ribosylation is a reversible post-translational modification, where ADP-ribose units are covalently attached to target protein side chains. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that plays a key role in physiological and pathological conditions. Studies have reported that ADP-ribosylation affects VEGF's ability to bind to VEGF receptors, impacting angiogenesis signalling. However, the specific amino acid undergoing ADP-ribosylation on VEGF remained unknown. To understand the mechanism of ADP-ribose addition to VEGF, an in silico study was designed. The study initially checked for the presence of any conserved motif where ADP-ribosylation could potentially occur and identified the presence of the EIE motif in VEGF, a probable site for ADP-ribosylation for many proteins. Subsequently, the amino acids near this motif were selected and their structural properties were analyzed. Surface-exposed amino acids were chosen, and ADP-ribose was then added to their side chains. The results revealed that the amino acids ASP (67) and GLU (70) underwent glycosidic linkage with ADP-ribose, indicating that they are the most probable modification sites. Subsequently, Molecular dynamic simulation analysis such as RMSD, RMSF, Rg, PCA, and FEL, along with MM-PBSA binding free energy calculations were performed to understand the stability of the VEGF-ADP-ribose complexes. The analysis revealed that amino acid at position 67 (ASP67) is the most probable site for ADP-ribosylation in VEGF.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3406-3414"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040039","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":"Recognition of human telomeric G-quadruplex DNA by 1,5-disubstituted diethyl-amido anthraquinone derivative in different ion environments causing thermal stabilization and apoptosis.","authors":"Anjana Kumari, Kumud Pandav, Mala Nath, Ritu Barthwal, Rama Krishna Peddinti","doi":"10.1080/07391102.2023.2298733","DOIUrl":"10.1080/07391102.2023.2298733","url":null,"abstract":"<p><p>Ligand binding to G-quadruplex (G4) structures at human telomeric DNA ends promotes thermal stabilization, disrupting the interaction of the telomerase enzyme, which is found active in 80-85% of cancers and serves as a molecular marker. Anthraquinone compounds are well-known G-quadruplex (G4) binders that inhibit telomerase and induce apoptosis in cancer cells. Our current investigation is based on 1,5-bis[3-(diethylamino)propionamido]anthracene-9,10-dione, a derivative of anthraquinone and its binding characterization with two different human telomeric DNA structures, wHTel26 and HTel22, in the effect of K⁺ and Na⁺ by using an array of biophysical, calorimetry, molecular docking and cell viability assay techniques. Binding constants (<i>K</i>_b) in the range of ∼10⁵-10⁷ M^-1 and stoichiometries of 1:1, 2:1 & 4:1 were obtained from the absorbance, fluorescence, and circular dichroism study. Remarkable hypochromism (55, 97%) and ∼17 nm shift in absorbance, fluorescence quenching (95, 97%), the unaltered value of fluorescence lifetime, restoration of Circular Dichroism bands, absence of ICD band, indicated the external groove binding/binding somewhere at loops. This is also evident in molecular docking results, the ligand binds to groove forming base (G4, G5, G24, T25) and in the vicinity to TTA loop (G14, G15, T17) bases of wHTel26 and HTel22, respectively. Thermal stabilization induced by ligand was found greater in Na⁺ ion (27.5 °C) than (19.1 °C) in K⁺ ion. Ligand caused cell toxicity in MCF-7 cancer cell lines with an IC₅₀ value of ∼8.4 µM. The above findings suggest the ligand, 1,5-bis[3-(diethylamino)propionamido]anthracene-9,10-dione could be a potent anticancer drug candidate and has great therapeutic implications.Binding of disubstituted amido anthraquinone derivative, 1,5-bis[3-(diethylamino)propionamido]anthracene-9,10-dione to human telomere HTel22 antiparallel conformation induced thermal stabilization.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3491-3507"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087022","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> evaluation of <i>Bismurrayaquinone-A</i> phytochemical as a potential multifunctional inhibitor targeting dihydrofolate reductase: implications for anticancer and antibacterial drug development.","authors":"Lei Qian, Mohammad Khalid, Mohammed H Alqarni, Sultan K Alshmmari, Mohammad Ali Abdullah Almoyad, Shadma Wahab, Abdulrhman Alsayari, Shao-Ji Li","doi":"10.1080/07391102.2023.2299306","DOIUrl":"10.1080/07391102.2023.2299306","url":null,"abstract":"<p><p>Dihydrofolate reductase (DHFR) has gained significant attention in drug development, primarily due to marked distinctions in its active site among different species. DHFR plays a crucial role in both DNA and amino acid metabolism by facilitating the transfer of monocarbon residues through tetrahydrofolate, which is vital for nucleotide and amino acid synthesis. This considers its potential as a promising target for therapeutic interventions. In this study, our focus was on conducting a virtual screening of phytoconstituents from the IMPPAT2.0 database to identify potential inhibitors of DHFR. The initial criterion involved assessing the binding energy of molecules against DHFR and we screened top 20 compounds ranging energy -13.5 to -11.4 (kcal/Mol) while Pemetrexed disodium bound with less energy -10.2 (kcal/Mol), followed by an analysis of their interactions to identify more effective hits. We prioritized IMPHY007679 (<i>Bismurrayaquinone-A</i>), which displayed a high binding affinity and crucial interaction with DHFR. We also evaluated the drug-like properties and biological activity of IMPHY007679. Furthermore, MD simulation was done, RMSD, RMSF, Rg, SASA, PCA and FEL explore the time-evolution impact of IMPHY007679 comparing it with a reference drug, Pemetrexed disodium. Collectively, our findings suggest that IMPHY007679 recommend further investigation in both <i>in vitro</i> and <i>in vivo</i> settings for its potential in developing anticancer and antibacterial therapies. This compound holds promise as a valuable candidate for advancing drug research and treatment strategies.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3570-3584"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074227","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":"Discovery of non-peptide GLP-1r natural agonists for enhancing coronary safety in type 2 diabetes patients.","authors":"Neda Shakour, Saeideh Hoseinpoor, Fatemeh Rajabian, Sabikeh G Azimi, Mehrdad Iranshahi, Hojjat Sadeghi-Aliabadi, Farzin Hadizadeh","doi":"10.1080/07391102.2023.2298734","DOIUrl":"10.1080/07391102.2023.2298734","url":null,"abstract":"<p><p>This study explores the computational discovery of non-peptide agonists targeting the Glucagon-Like Peptide-1 Receptor (GLP-1R) to enhance the safety of major coronary outcomes in individuals affected by Type 2 Diabetes. The objective is to identify novel compounds that can activate the GLP-1R pathway without the limitations associated with peptide agonists. Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD) and mortality, which is attributed to the accumulation of fat in organs, including the heart. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are frequently used to manage T2DM and could potentially offer cardiovascular benefits. Therefore, this study examines non-peptide agonists of GLP-1R to improve coronary safety in type 2 diabetes patients. After rigorous assessments, two standout candidates were identified, with natural compound <b>12</b> emerging as the most promising. This study represents a notable advancement in enhancing the management of coronary outcomes among individuals with type 2 diabetes. The computational methodology employed successfully pinpointed potential GLP-1R natural agonists, providing optimism for the development of safer and more effective therapeutic interventions. Although computational methodologies have provided crucial insights, realizing the full potential of these compounds requires extensive experimental investigations, crucial in advancing therapeutic strategies for this critical patient population.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3508-3525"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074229","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":"Improving protein-ligand docking results using the Semiempirical quantum mechanics: testing on the PDBbind 2016 core set.","authors":"Zainab Mohebbinia, Rohoullah Firouzi, Mohammad Hossein Karimi-Jafari","doi":"10.1080/07391102.2023.2299742","DOIUrl":"10.1080/07391102.2023.2299742","url":null,"abstract":"<p><p>Molecular docking techniques are routinely employed for predicting ligand binding conformations and affinities in the <i>in silico</i> phase of the drug design and development process. In this study, a reliable semiempirical quantum mechanics (SQM) method, PM7, was employed for geometry optimization of top-ranked poses obtained from two widely used docking programs, AutoDock4 and AutoDock Vina. The PDBbind core set (version 2016), which contains high-quality crystal protein - ligand complexes with their corresponding experimental binding affinities, was used as an initial dataset in this research. It was shown that docking pose optimization improves the accuracy of pose predictions and is very useful for the refinement of docked complexes <i>via</i> removing clashes between ligands and proteins. It was also demonstrated that AutoDock Vina achieves a higher sampling power than AutoDock4 in generating accurate ligand poses (RMSD ≤ 2.0 Å), while AutoDock4 exhibits a better ranking power than AutoDock Vina. Finally, a new protocol based on a combination of the results obtained from the two docking programs was proposed for structure-based virtual screening studies, which benefits from the robust sampling abilities of AutoDock Vina and the reliable ranking performance of AutoDock4.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3602-3612"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080587","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":"Prediction of interface between regions of varying degrees of order or disorderness in intrinsically disordered proteins from dihedral angles.","authors":"Babli Sharma, Venkata Satish Kumar Mattaparthi","doi":"10.1080/07391102.2023.2294837","DOIUrl":"10.1080/07391102.2023.2294837","url":null,"abstract":"<p><p>Intrinsically disordered proteins (IDPs) are proteins that do not form uniquely defined three-dimensional (3-D) structures. Experimental research on IDPs is difficult since they go against the traditional protein structure-function paradigm. Although there are several predictors of disorder based on amino acid sequences, but very limited based on the 3-D structures of proteins. Dihedral angles have a significant role in predicting protein structure because they establish a protein's backbone, which, coupled with its side chain, establishes its overall shape. Here, we have carried out atomistic Molecular Dynamics (MD) simulations on four different proteins: one ordered protein (Monellin), two partially disordered proteins (p53-TAD and Amyloid beta (Aβ_1-42) peptide), and one completely disordered protein (Histatin 5). The MD simulation trajectories for the corresponding four proteins were used to conduct dihedral angle (ϕ and ѱ) analysis. Then, the average dihedral angles for each of the residues were calculated and plotted against the residue index. We noticed steep rises or falls in the average ϕ value at certain locations in the plot. These sudden shifts in the average ϕ value reflect the interface between regions of varying degrees of order or disorderness in intrinsically disordered proteins. Using this method, the probable conformer of a protein with a higher degree of disorder can be found among the ensembles of structures sampled during the MD simulations. The results of our study offer new understandings on precisely identifying regions of various degrees of disorder in intrinsically disordered proteins.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3005-3015"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138804087","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}