Journal of Biomolecular Structure & Dynamics最新文献

{"title":"A virtual insight into mushroom secondary metabolites: 3D-QSAR, docking, pharmacophore-based analysis and molecular modeling to analyze their anti-breast cancer potential.","authors":"Nusrat Shafiq, Bushra Shakoor, Nazia Yaqoob, Shagufta Parveen, Simone Brogi, Ahmad Mohammad Salamatullah, Maryam Rashid, Mohammed Bourhia","doi":"10.1080/07391102.2024.2304137","DOIUrl":"10.1080/07391102.2024.2304137","url":null,"abstract":"<p><p>Breast cancer is a major issue of investigation in drug discovery due to its rising frequency and global dominance. Plants are significant natural sources for the development of novel medications and therapies. Medicinal mushrooms have many biological response modifiers and are used for the treatment of many physical illnesses. In this research, a database of 89 macro-molecules with anti-breast cancer activity, which were previously isolated from the mushrooms in literature, has been selected for the three-dimensional quantitative structure-activity relationships (3D-QSAR) studies. The 3D-QSAR model was necessarily used in Pharmacopoeia virtual evaluation of the database to develop novel MCF-7 inhibitors. With the known potential targets of breast cancer, the docking studies were achieved. Using molecular dynamics simulations, the targets' stability with the best-chosen natural product molecule was found. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity of three compounds, resulting after the docking study, were predicted. The compound <b>C1</b> (Pseudonocardian A) showed the features of effective compounds because it has bioavailability from different coral species and is toxicity-free for the prevention of many dermatological illnesses. <b>C1</b> is chemically active and possesses charge transfer inside the monomer, as seen by the band gaps of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) electrons. The reactivity descriptors ionization potential, electron affinity, chemical potential (μ), hardness (η), softness (S), electronegativity (χ), and electrophilicity index (ω) have been estimated using the energies of frontier molecular orbitals (HOMO-LUMO). Additionally, molecular electrostatic potential maps were created to show that the <b>C1</b> is reactive.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4512-4533"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650828","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 accessibility studies highlight the differential binding of clemizole to TRPC5 and TRPC6.","authors":"Uzma Saqib, Isaac S Demaree, Alexander G Obukhov, Mirza S Baig, Mohd Shahnawaz Khan, Nojood Altwaijry, Mochammad Arfin Fardiansyah Nasution, Kenji Mizuguchi, Krishnan Hajela","doi":"10.1080/07391102.2024.2306198","DOIUrl":"10.1080/07391102.2024.2306198","url":null,"abstract":"<p><p>Transient Receptor Potential Canonical 5 (T RP C5) and T RP C6 channels play critical physiological roles in various cell types. Their involvement in numerous disease progression mechanisms has led to extensive searches for their inhibitors. Although several potent T RP C inhibitors have been developed and the structure of their binding sites were mapped using cryo electron microscopy, a comprehensive understanding of the molecular interactions within the inhibitor binding site of T RP Cs remains elusive. This study aimed to decipher the structural determinants and molecular mechanisms contributing to the differential binding of clemizole to T RP C5 and T RP C6, with a particular focus on the accessibility of binding site residues. This information can help better understand what molecular features allow for selective binding, which is a key characteristic of clinically effective pharmacological agents. Using computational methodologies, we conducted an in-depth molecular docking analysis of clemizole with T RP C5 and T RP C6 channels. The protein structures were retrieved from publicly accessible protein databases. Discovery Studio 2020 Client Visualizer and Chimera software facilitated our in-silico mutation experiments and enabled us to identify the critical structural elements influencing clemizole binding. Our study reveals key molecular determinants at the clemizole binding site, specifically outlining the role of residues' Accessible Surface Area (ASA) and Relative Accessible Surface Area (RASA) in differential binding. We found that lower accessibility of T RP C6 binding site residues, compared to those in T RP C5, could account for the lower affinity binding of clemizole to T RP C6. This work illuminates the pivotal role of binding site residue accessibility in determining the affinity of clemizole to T RP C5 and T RP C6. A nuanced understanding of the distinct binding properties between these homologous proteins may pave the way for the development of more selective inhibitors, promising improved therapeutic efficacy and fewer off-target effects. By demystifying the structural and molecular subtleties of T RP C inhibitors, this research could significantly accelerate the drug discovery process, offering hope to patients afflicted with T RP C-related diseases.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4729-4742"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation, characterization and evaluation of oxypeucedanin and osthol from local endemic <i>Prangos aricakensis</i> Behçet and Yapar root as antioxidant, enzyme inhibitory, antibacterial and DNA protection: molecular docking and DFT approaches.","authors":"Serbay Şafak Gökçimen, Yaşar İpek, Lütfi Behçet, İbrahim Demirtaş, Tevfik Özen","doi":"10.1080/07391102.2024.2303387","DOIUrl":"10.1080/07391102.2024.2303387","url":null,"abstract":"<p><p><i>Prangos</i> species were previously used against many disorders due to their chemical component. <i>Prangos aricakensis</i> Behçet & Yapar is a newly discovered local endemic species in Turkey's eastern region, and there is no research on <i>P. aricakensis</i> in the literature. In this work, oxypeucedanin and osthol molecules have been isolated from the root part of <i>P. aricakensis</i> for the first time. Oxypeucedanin and osthol structures were elucidated by 1D and 2D NMR analysis. For the bioactivities determination, antioxidant (DPPH^· and ABTS^·+ scavenging), enzyme inhibition (AChE, BChE, tyrosinase, and urease), antibacterial and DNA protection activity studies were applied for both molecules and compared with standard drug molecules, after applying enzyme kinetic assays and <i>in silico</i> approaches to clarify the mechanism of action for both molecules with enzymes, using molecular docking and density functional theory (DFT). Oxypeucedanin (2.19 ± 0.38 µg/mL) and osthol (4.57 ± 1.28 µg/mL) exhibited better activity than standards in DPPH^∙ scavenging activity. Osthol (11.76 ± 0.59 µg/mL) showed a better tyrosinase inhibition effect than kojic acid (12.82 ± 0.91 µg/mL), and oxypeucedanin (3.03 ± 0.01 µg/mL) showed better urease inhibition effect than thiourea (5.37 ± 1.86 µg/mL). Our results showed that the osthol molecule was an excellent skin protective agent while the oxypeucedanin molecule could be a remarkable antiulcer agent. Therefore, although this study is the first in its field, it remained in the <i>in vitro</i> and <i>in silico</i> stages and is thought to pave the way for <i>in vivo</i> studies in the future.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4494-4511"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424821","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 investigation of RPS6KB1 associated cancer inhibitor: a drug repurposing study.","authors":"Saravanan Rajendrasozhan, Irfan Ahmad, Safia Obaidur Rab, Mohammad Y Alshahrani, Eman Abdullah Almuqri, Jamshaid Ahmad Siddiqui, Md Mushtaque","doi":"10.1080/07391102.2024.2304679","DOIUrl":"10.1080/07391102.2024.2304679","url":null,"abstract":"<p><p>The ribosomal protein S6 kinase beta-1 (RPS6KB1), also known as p70S6 kinase, plays a crucial role in various disease-related conditions such as diabetes, obesity, and cancer. Its activity is regulated by phosphorylation events, including phosphorylation of Threonine 389 in the hydrophobic motif by the mammalian target of rapamycin complex 1 (mTORC1) and phosphorylation of Threonine 229 in the activation loop by PDK1 (phosphoinositide-dependent kinase 1). However, other phenomena connected to RPS6KB1 remain unknown. In this study, we employed virtual screening and molecular docking techniques on the molecules in the ZINC library to identify potential inhibitors. Molecular dynamics (MD) simulations and MMGBSA calculations were carried out on promising compounds to determine their binding affinity and stability. We also evaluated the drug-likeness properties of the selected compounds. A comparative study between the native RPS6KB1 structure, co-crystal ligands, and the shortlisted molecules from the ZINC dataset was carried out. The identified molecules possess significant potential for future <i>in vitro</i> and <i>in vivo</i> studies, paving the way for developing effective cancer treatments.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4678-4685"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491502","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 the interactions of repositioning and known drugs for Alzheimer's disease with hen egg white lysozyme by MM-GBSA.","authors":"Amit Kumar Halder, Puja Mishra, Souvik Basak, Debjani Roy, Anurag Das, Sucheta Karmakar, Ritam Mondal, Shrestha Banerjee, Prakarsha De, Ankit Chatterjee, Susmita Mallick, Abhijit Hazra","doi":"10.1080/07391102.2024.2305697","DOIUrl":"10.1080/07391102.2024.2305697","url":null,"abstract":"<p><p>Six drugs (dapsone, diltiazem, timolol, rosiglitazone, mesalazine, and milnacipran) that were predicted by network-based polypharmacology approaches as potential anti-Alzheimer's drugs, have been subjected in this study for <i>in silico</i> and <i>in vitro</i> evaluation to check their potential against protein fibrillation, which is a causative factor for multiple diseases such as Alzheimer's disease, Parkinson's disease, Huntington disease, cardiac myopathy, type-II diabetes mellitus and many others. Molecular docking and thereafter molecular dynamics (MD) simulations revealed that diltiazem, rosiglitazone, and milnacipran interact with the binding residues such as Asp52, Glu35, Trp62, and Asp101, which lie within the fibrillating region of HEWL. The MM-GBSA analysis revealed -7.86, -5.05, and -10.29 kcal/mol as the binding energy of diltiazem, rosiglitazone, and milnacipran. The RMSD and RMSF calculations revealed significant stabilities of these ligands within the binding pocket of HEWL. While compared with two reported ligands inhibiting HEWL fibrillation, milnacipran depicted almost similar binding potential with one of the known ligands (Ligand binding affinity -10.66 kcal/mol) of HEWL. Furthermore, secondary structure analyses revealed notable inhibition of the secondary structural changes with our candidate ligand; especially regarding retention of the 3/10 α-helix both by DSSP simulation, Circular dichroism, and FESEM-based microscopic image analyses. Taking further into experimental validation, all three ligands inhibited fibrillation in HEWL in simulated conditions as revealed by blue shift in Congo red assay and later expressing percentage inhibition in ThioflavinT assay as well. However, dose-dependent kinetics revealed that the antifibrillatory effects of drugs are more pronounced at low protein concentrations.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4629-4647"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491504","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":"Effectiveness of sesquiterpene derivatives from Cinnamomum genus in nicotine replacement therapy through blocking acetylcholine nicotinate: a computational analysis.","authors":"Aden Dhana Rizkita, Sintia Ayu Dewi, Taufik Muhammad Fakih, Cheng-Chung Lee","doi":"10.1080/07391102.2024.2305315","DOIUrl":"10.1080/07391102.2024.2305315","url":null,"abstract":"<p><p>Cigarette smoking poses various health risks, such as increasing the susceptibility to respiratory infections, contributing to osteoporosis, causing reproductive issues, delaying postoperative recovery, promoting ulcer formation and heightening the risk of diabetes. While many harmful effects of smoking are attributed to other cigarette components, it is nicotine's pharmacological effects that underlie tobacco addiction. Nicotine replacement therapy (NRT) aims to alleviate the urge to smoke and mitigate physiological and psychomotor withdrawal symptoms by delivering nicotine. This study explores the potential of sesquiterpene derivative compounds derived from the Cinnamomum genus using computational techniques. The research incorporates molecular docking analyses, Lipinski's rule of five filtration for drug-likeness, pharmacokinetic and toxicity predictions to assess safety profiles and molecular dynamics (MD) simulations to gauge interaction stability. The findings reveal that all sesquiterpene derivative compounds from the Cinnamomum genus can potentially inhibit nicotinic acetylcholine receptors (nAChRs), particularly nAChRÿ7. However, only abscisic acid exhibit active inhibition, along with suitable drug properties, pharmacokinetics and toxicity profiles. MD studies confirm the stability of interactions between abscisic acid with nAChRÿ7. Consequently, abscisic acid, as sesquiterpene derivatives from the Cinnamomum genus, holds substantial promise for further investigation as nAChRÿ7 inhibitors.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4770-4783"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546497","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 mechanism, photo-induced cleavage and computational studies of interaction cefepime drug with Human serum albumin.","authors":"Waddhaah M Al-Asbahy, Manal Shamsi, Ahmed Senan, Niyazi Al-Areqi","doi":"10.1080/07391102.2024.2304668","DOIUrl":"10.1080/07391102.2024.2304668","url":null,"abstract":"<p><p>The binding interaction of cefepime to human serum albumin (HSA) in aqueous solution was investigated by molecular spectroscopy (UV spectra, fluorescence spectra and CD spectra), photo-cleavage and modeling studies under simulative physiological conditions. Spectrophotometric results are rationalized in terms of a static quenching process and binding constant (<i>K_b</i>) and the number of binding sites (<i>n</i> ≈ 1) were calculated using fluorescence quenching approaches at three temperature settings. Thermodynamic data of <i>ΔG</i>, <i>ΔH</i> and ΔS at different temperatures were evaluated. The results showed that the electrostatic and hydrogen bonding interactions play a major role in the binding of cefepime to HSA. The value of 3.4 nm for the distance <i>r</i> between the donor (HSA) and acceptor (cefepime) was derived from the fluorescence resonance energy transfer (FRET). FTIR and CD measurements has been reaffirmed HSA-cefepime association and demonstrated reduction in <i>α</i>-helical content of HSA. Furthermore, the study of molecular modeling also indicated that cefepime could strongly bind to the site I (subdomain IIA) of HSA. Additionally, cefepime shows efficient photo- cleavage of HSA cleavage. Our results may provide valuable information to understand the pharmacological profile of cefepime drug delivery in blood stream.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4648-4658"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485600","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 modeling and simulation studies of SELEX-derived high-affinity DNA aptamers to the Ebola virus nucleoprotein.","authors":"D R Martin, A T Mutombwera, A M Madiehe, M O Onani, M Meyer, R Cloete","doi":"10.1080/07391102.2024.2302922","DOIUrl":"10.1080/07391102.2024.2302922","url":null,"abstract":"<p><p>Ebola viral disease (EVD) is a highly infectious and potentially fatal illness with a case fatality rate ranging from 25% to 90%. To effectively control its spread, there is a need for rapid, reliable and lowcost point-of-care (P OC) diagnostic tests. While various EVD diagnostic tests exist, few are P OC tests, and many are not cost-effective. The use of antibodies in these tests has limitations, prompting the exploration of aptamers as potential alternatives. Various proteins from the Ebola virus (EBOV) proteome, including EBOV nucleoprotein (NP), are considered viable targets for diagnostic assays. A previous study identified three aptamers (Apt1. Apt2 and Apt3) with high affinity for EBOV NP using systemic evolution of ligands by exponential enrichment (SELEX). This study aimed to employ in silico methods, such as Phyre2, RNAfold, RNAComposer, HADDOCK and GROMACS, to model the structures of EBOV NP and the aptamers, and to investigate their binding. The in silico analysis revealed successful binding of all the three aptamers to EBOV NP, with a suggested ranking of Apt1 > Apt2 > Apt3 based on binding affinity. Microscale thermophoresis (MST) analysis confirmed the binding, providing dissociation constants of 25 ± 2.84, 56 ± 2.76 and 140 ±3.69 nM for Apt1, Apt2 and Apt3, respectively. The study shows that the findings of the in silico analysis was in agreement with the MST analysis. Inclusion of these in silico approaches in diagnostic assay development can expedite the selection of candidate aptamers, potentially overcoming challenges associated with aptamer application in diagnostics.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4405-4422"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466539","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":"High-throughput computational screening for identification of potential hits against bacterial Acriflavine resistance protein B (AcrB) efflux pump.","authors":"Sanket Rathod, Sreenath Dey, Prafulla Choudhari, Deepak Mahuli, Sneha Rochlani, Rakesh Dhavale, Somdatta Chaudhari, Yasinalli Tamboli, Jaydeo Kilbile, Eerappa Rajakumara","doi":"10.1080/07391102.2024.2302936","DOIUrl":"10.1080/07391102.2024.2302936","url":null,"abstract":"<p><p>Antibiotic resistance is a pressing global health challenge, driven in part by the remarkable efflux capabilities of efflux pump in AcrB (Acriflavine Resistance Protein B) protein in Gram-negative bacteria. In this study, a multi-approached computational screening strategy encompassing molecular docking, <i>In silico</i> absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis, druglikeness assessment, molecular dynamics simulations and density functional theory studies was employed to identify novel hits capable of acting against AcrB-mediated antibiotic resistance. Ligand library was acquired from the COCONUT database. Performed computational analyses unveiled four promising hit molecules (CNP0298667, CNP0399927, CNP0321542 and CNP0269513). Notably, CNP0298667 exhibited the highest negative binding affinity of -11.5 kcal/mol, indicating a possibility of strong potential to disrupt AcrB function. Importantly, all four hits met stringent druglikeness criteria and demonstrated favorable <i>in silico</i> ADMET profiles, underscoring their potential for further development. MD simulations over 100 ns revealed that the CNP0321542-4DX5 and CNP0269513-4DX5 complexes formed robust and stable interactions with the AcrB efflux pump. The identified hits represent a promising starting point for the design and optimization of novel therapeutics aimed at combating AcrB-mediated antibiotic resistance in Gram-negative bacteria.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4423-4439"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139540809","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 analysis of bevacizumab binding with protein receptors for its potential anticancer activity.","authors":"Nada Alsakhen, Enas S Radwan, Imran Zafer, Husam Abed Alfattah, Israa M Shamkh, Md Tabish Rehman, Moayad Shahwan, Khalid Ali Khan, Shimaa A Ahmed","doi":"10.1080/07391102.2024.2307445","DOIUrl":"10.1080/07391102.2024.2307445","url":null,"abstract":"<p><p>Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments. In this study, we investigated the binding free energy (Δ<i>G</i>) of bevacizumab, an anti-cancer therapy targeting angiogenesis through the inhibition of vascular endothelial growth factor (VEGF), with various proto-oncogenes including CDK4, EGFR, frizzled, IGFR, OmoMYC, and KIT. Our in-silico investigation revealed that hydrogen bonding is pivotal in inducing conformational changes within the DNA structure, impeding its replication and preventing cell death. Molecular docking results revealed the presence of crucial hydrogen bonds and supported the formation of stable bevacizumab complexes. The molecular docking scores for the tested complexes were CDK4 (Score = -7.2 kcal/mol), EGFR (Score = -8.5 kcal/mol), frizzled (Score = -6.9 kcal/mol), IGFR (Score = -7.8 kcal/mol), KIT (Score = -6.5 kcal/mol), and MYC (Score = -8.3 kcal/mol). The binding mode demonstrated vital hydrogen bonds correlated with the observed energy gap. Notably, the calculated binding free energies of the tested compounds are as follows: CDK4 (Δ<i>G</i> = 24275.195 ± 6411.293 kJ/mol), EGFR (Δ<i>G</i> = 363273.625 ± 8731.466 kJ/mol), frizzled (Δ<i>G</i> = 181751.990 ± 28438.515 kJ/mol), IGFR (Δ<i>G</i> = 162414.725 ± 10728.367 kJ/mol), KIT (Δ<i>G</i> = 40162.585 ± 4331.017 kJ/mol), and MYC (Δ<i>G</i> = 434783.463 ± 53989.676 kJ/mol). Furthermore, through extensive 100 ns MD simulations, we observed the formation of a stable bevacizumab complex structure. The simulations confirmed the stability of the bevacizumab complex with the proto-oncogenes. The results of this study highlight the potential of bevacizumab complex as a promising candidate for anticancer treatment. The identification of hydrogen bonding, along with the calculated binding free energies and molecular docking scores, provides valuable insights into the molecular interactions and stability of the bevacizumab complexes. These findings and the extensive MD simulations open new avenues for future research and development of bevacizumab as a targeted therapy for breast cancer and other related malignancies.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4814-4834"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570012","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}