Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Computational insights into pediatric adenovirus inhibitors: <i>in silico</i> strategies for drug repurposing.","authors":"Kaushik Sarkar, Subrata Nandi, Rajesh Kumar Das","doi":"10.1080/07391102.2023.2252072","DOIUrl":"10.1080/07391102.2023.2252072","url":null,"abstract":"<p><p>Human adenovirus (HADV) infection can pose a serious threat to children, leading to a variety of respiratory illnesses and other complications. Particularly, children with weak immune systems are vulnerable to severe adenovirus infections with high mortality. The main focus of this study is to propose new antiviral agents as lead HADV inhibitors for children. So, several antiviral agents used in children were subjected to finding new HADV inhibitors using important computational methods of molecular docking, molecular dynamics (MD) simulation, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) binding free energy calculations, density functional theory (DFT), and pharmacokinetic analysis. Molecular docking of standard cidofovir along with other ligands, suggested that sofosbuvir has the highest binding energy (-10.8 kcal/mol), followed by baloxavir marboxil (-10.36 kcal/mol). Further, the analysis of molecular interactions using MD simulation (100 ns) and MM-PBSA indicated that baloxavir marboxil has formed the most stable protein-ligand complex with HADV, followed by sofosbuvir. The binding free energies of baloxavir marboxil and sofosbuvir were found to be -61.724 kJ/mol and -48.123 kJ/mol, respectively. The DFT and drug-likeness properties of these compounds were also investigated. Overall, two antiviral agents, such as baloxavir marboxil, and sofosbuvir are suggested as lead repurposed candidates against HADV.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"9614-9627"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10109431","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":"Synthesis, anticancer activity and molecular modeling study of novel substituted triazole linked tetrafluoronaphthalene hybrid derivatives.","authors":"Musa Erdoğan, Ferah Comert Onder","doi":"10.1080/07391102.2023.2252914","DOIUrl":"10.1080/07391102.2023.2252914","url":null,"abstract":"<p><p>To create some novel anticancer molecules, a library of novel series of various triazoles linked to the hydroxyl group of 5,6,7,8-tetrafluoronaphthalen-1-ol <b>(3)</b> was designed and synthesized <i>via</i> CuAAC reaction '<i>Click Chemistry'</i> of tetrafluoronaphthalene based terminal alkyne with substituted organic azides. The structural characterizations of the targeted Click products <b>9-18</b> were confirmed by FTIR, ¹H NMR, ¹⁹F NMR, ¹³C NMR and HRMS spectroscopy. Synthesized compounds were tested in two triple negative breast cancer (TNBC) cell lines to understand their anticancer potentials. According to our findings, compounds <b>14</b> and <b>13</b> showed high cytotoxicity in BT549 cells at 20 μM and 30 μM, respectively. Moreover, these compounds blocked the migration of BT549 cells. In the MDA-MB-231 cell line, compound <b>18</b> exhibited high cytotoxicity and can block cell migration for 24 h. Molecular docking study with synthesized novel compounds was performed by Glide/SP method against SphK1 drug target. Furthermore, molecular dynamics (MD) simulation was carried out for the compounds <b>12-14</b> and <b>18</b>. The compounds <b>13</b> and <b>14</b> may be potential inhibitor candidates in place of a reference inhibitor. A pharmacophore model was generated with the most potent compound <b>14</b>, and the approved drugs were screened using the modules of Discovery Studio to find similar drugs. Consequently, this comprehensive study encompassing design, synthesis, <i>in vitro</i> and <i>in silico</i> analyses were correlated with the structure-activity relationship between compounds. The findings have the potential to unveil promising drug candidates for future studies.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"9767-9786"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10168516","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":"Molecularly imprinted polymer-based sensors for identification volatile compounds in pharmaceutical products: in silico rational design.","authors":"Taufik Muhammad Fakih","doi":"10.1080/07391102.2023.2252090","DOIUrl":"10.1080/07391102.2023.2252090","url":null,"abstract":"<p><p>The present study aimed to strategically design a Molecularly Imprinted Polymer (MIP) with selective extraction capabilities for volatile compounds found in pork. These specific volatile compounds, such as 3-methyl-1-butanol, 1-nonanal, octanal, hexanal, 2-pentyl-furan, 1-penten-3-one, N-morpholinomethyl-isopropyl-sulfide, methyl butyrate, and (E,E)-2,4-decadienal, are primarily responsible for the distinctive aroma and flavor characteristics associated with pork. Molecular dynamics simulations were employed to investigate the stability of the pre-polymerization system, simulating the interactions between the volatile compounds as templates, 4-hydroxyethyl methacrylate (HEMA) as monomers, and ethylene glycol dimethacrylate (EGDMA) as crosslinkers. Computational simulations revealed that the optimal mole ratio of 1:4:20 for templates, monomers, and crosslinkers resulted in the most favorable functional radial distribution and exhibited the strongest interactions. To validate the computational findings, additional analyses were performed utilizing Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA), radial distribution function (RDF), and hydrogen bond (HBond) occupancy. The calculated binding free energy demonstrated that all template molecules were capable to bind with both the monomers and crosslinkers, including 1-penten-3-one and N-morpholinomethyl-isopropyl-sulfide displaying the strongest interactions, with values of -12,674 kJ/mol and -11,646 kJ/mol, respectively. The congruence between the results obtained from the molecular simulation analyses highlights the crucial role of molecular dynamics simulations in the study and development of MIP for the analysis of marker compounds present in pork.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"9639-9649"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10103249","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":"Categorization of hotspots into three types - weak, moderate and strong to distinguish protein-protein <i>versus</i> protein-peptide interactions.","authors":"Kiran Kumar A, R S Rathore","doi":"10.1080/07391102.2023.2252077","DOIUrl":"10.1080/07391102.2023.2252077","url":null,"abstract":"<p><p>Protein-protein and protein-peptide interactions (PPI and PPepI) belong to a similar category of interactions, yet seemingly subtle differences exist among them. To characterize differences between protein-protein (PP) and protein-peptide (PPep) interactions, we have focussed on two important classes of residues-hotspot and anchor residues. Using implicit solvation-based free energy calculations, a very large-scale alanine scanning has been performed on benchmark datasets, consisting of over 5700 interface residues. The differences in the two categories are more pronounced, if the data were divided into three distinct types, namely - weak hotspots (having binding free energy loss upon Ala mutation, ΔΔG, ∼2-10 kcal/mol), moderate hotspots (ΔΔG, ∼10-20 kcal/mol) and strong hotspots (ΔΔG ≥ ∼20 kcal/mol). The analysis suggests that for PPI, weak hotspots are predominantly populated by polar and hydrophobic residues. The distribution shifts towards charged and polar residues for moderate hotspot and charged residues (principally Arg) are overwhelmingly present in the strong hotspot. On the other hand, in the PPepI dataset, the distribution shifts from predominantly hydrophobic and polar (in the weak type) to almost similar preference for polar, hydrophobic and charged residues (in moderate type) and finally the charged residue (Arg) and Trp are mostly occupied in the strong type. The preferred anchor residues in both categories are Arg, Tyr and Leu, possessing bulky side chain and which also strike a delicate balance between side chain flexibility and rigidity. The present knowledge should aid in effective design of biologics, by augmentation or disruption of PPIs with peptides or peptidomimetics.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"9348-9360"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10476954","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 toxicity of type II ribosome inactivating proteins (RIPs): a molecular dynamics study.","authors":"Pavan K Madasu, Thyageshwar Chandran","doi":"10.1080/07391102.2024.2419855","DOIUrl":"https://doi.org/10.1080/07391102.2024.2419855","url":null,"abstract":"<p><p>Ribosome Inactivating Proteins (RIPs) act by irreversibly depurinating the 28S rRNA ricin-sarcin loop (SRL) of the eukaryotic ribosome resulting in protein synthesis inhibition. In general, they consist of two variants: Type I which is single chained (∼30 kDa), and Type II, a more toxic variant which is a Type I N-glycosidase chain covalently linked to a lectin chain. These proteins are believed to play a pivotal role in defence mechanisms. Intriguingly, non-toxic variants of such toxic proteins do exist in nature. To explore their mode of action, in the present study we have selected three toxic (Ricin, Ebulin and HmRIP) as well as two non-toxic (BGSL and SGSL) RIPs and performed molecular docking and molecular dynamic simulations with the SRL loop. This study throws light on the structural stability and plasticity of the toxic and non-toxic RIP complexes. Furthermore, analysis of the active site cavity volume and binding free energy calculations reveal that the SRL, particularly the specific adenine (A4605), is relatively unstable in the case of non-toxic RIPs which is also supported by the free binding energy calculations, and the pocket size analysis indicates the abnormal increase in active site cavity volume of non-toxic RIPs with time. This first-of-its-kind comprehensive study of toxic and non-toxic RIPs gives insights about the mode of action and the dynamic nature of their interaction with the SRL loop. These observations will be helpful in the development of toxoids against RIPs and also in designing novel therapeutic approaches against human diseases.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501145","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":"Unraveling the therapeutic potential of <i>Satureja nabateorum</i> extract: inducing apoptosis and cell cycle arrest through p53, Bax/Bcl-2, and caspase-3 pathways in human malignant cell lines, with in silico insights.","authors":"Bader Huwaimel, Hamdoon A Mohammed, Akram M Elkashlan, Radwan Alnajjar, Osama A Altamimi, Meshal M Alorainan, Meshari K Altuwayhir, Salman F Algharby, Suliman A Almahmoud, Amr S Abouzied","doi":"10.1080/07391102.2024.2419863","DOIUrl":"https://doi.org/10.1080/07391102.2024.2419863","url":null,"abstract":"<p><p><i>Satureja nabateorum</i>, known as Nabatean savory is a Lamiaceae plant native to the Arabian Peninsula, specifically in the mountainous regions of Saudi Arabia. The study aims to investigate the phytochemical components of the <i>S. nabateorum</i> leaves (SNL) and stems (SNS) extract and to assess their antioxidant, antimicrobial, and antiproliferative properties. Methanol extracts from leaves and stems were analyzed for chemical constituents using the GC-MS technique. Antioxidant capacities were measured using hydrogen peroxide and ABTS radical-scavenging methods, and antimicrobial activity was tested against various microorganisms. Cytotoxic activity on four human malignant cell lines was assessed using MTT and flow cytometry. Molecular docking and molecular dynamics studies were conducted to understand the interactions and binding modes of the extracted compounds at a molecular level. GC-MS analysis of SNL extract revealed thymol, carvacrol, and p-cymen-8-ol as major constituents. SNS extract contained β-sitosterol, stigmasterol, lupeol, and lup-20(29)-ene-3β,28-diol. SNS extract exhibited more potent antioxidant, antimicrobial, and anticancer effects than SNL extract. The extract, SNS, exhibited potential toxicity in A549 cells with an IC₅₀ value of 3.62 µg/mL and induced marked apoptotic effects with S phase-cell cycle arrest. SNS extract also showed higher levels of Caspase 3, Bax, p53, and the Bax/Bcl2 ratio and lower levels of Bcl-2. Molecular docking and dynamic simulation supported these findings, targeting the EGFR TK domain. The study suggests that the <i>S. nabateorum</i> stem extract holds promise as a potent antimicrobial, antioxidant, and anticancer agent. It provides valuable insights for considering the extract as a substitute for chemotherapy and/or protective agents.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501146","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 modeling to understand the interaction of TMPyP4 with a G-quadruplex.","authors":"Senal D Liyanage, Jerrano L Bowleg, Steven R Gwaltney","doi":"10.1080/07391102.2024.2417378","DOIUrl":"https://doi.org/10.1080/07391102.2024.2417378","url":null,"abstract":"<p><p>The potential of small molecules to bind to G-quadruplex-forming sequences in oncogene promoter regions, thereby regulating their structural equilibrium, has been explored as a promising strategy for cancer chemotherapy. The model drug 5,10,15,20-tetrakis-(N-methyl-4-pyridyl)porphine (TMPyP4) has been shown to have an affinity toward G-quadruplex DNA. However, the precise sites and modes of TMPyP4 binding to G-quadruplex DNA remain a subject of debate. In this study, we focus on identifying potential binding sites on a mutant c-MYC sequence known to fold into a single 1:2:1 loop isomer quadruplex. Our findings provide insights into the 4:1 stoichiometry reported for TMPyP4 binding to this G-quadruplex. Binding enthalpy and free energy calculations show that intercalation of a TMPyP4 molecule between the quadruplexes is thermodynamically favorable. Our calculations suggest that two of the binding sites are located at the top and bottom of the quadruplex, respectively, while the remaining two are likely intercalations.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-7"},"PeriodicalIF":2.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501144","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 docking, network pharmacology, and QSAR modelling studies of benzo[c]phenanthridines - novel antileishmaniasis agents.","authors":"David Kikaawa, E Vadivel","doi":"10.1080/07391102.2024.2417226","DOIUrl":"https://doi.org/10.1080/07391102.2024.2417226","url":null,"abstract":"<p><p>Leishmaniasis treatment primarily relies on chemotherapy due to lack of vaccines. However, the low efficacy, parasite resistance, and toxicity associated with existing drugs necessitate the development of effective and safer therapies. Fuchino <i>et al</i>. reported promising leishmanicidal activity in a series of benzo[c]phenanthridines against <i>L. major</i> promastigotes. To progress these compounds towards drug development, it is crucial to understand their molecular targets, mechanisms of action, binding interactions, and structural requirements. In this research, molecular docking, network pharmacology, 2D-QSAR, and 3D-QSAR CoMFA studies were performed on 30 benzo[c]phenanthridines. Docking analysis showed that all molecules had a strong binding affinity to <i>L. major</i>-nucleoside diphosphate kinase (NDPK) compared to the other targets. 10-isopropoxy sanguinarine had the highest binding affinity (-10.6 kcal/mol) and formed ionic and hydrophobic interactions. Network pharmacology analysis of the most active compounds identified serine/threonine-protein kinase Mtor as a potential antileishmaniasis target in humans for benzo[c]phenanthridines. This was confirmed with high-affinity scores > -7.0 kcal/mol for all the compounds docked. GO and KEGG pathway enrichment identified Reg. of fatty acid oxidation (BP), TORC1 complex (CC), RNA polymerase III type 1 promoter sequence-specific DNA binding (MF), and Acute myeloid leukemia (KEGG pathway) to be highly enriched with the hub genes. Both 2D and 3D-QSAR CoMFA models satisfied the internal and external validation tests as follows: 2D-QSAR: R²_Train = 0.9040, Q²cv = 0.8648, R²adj = 0.8838, and R²_Test = 0.8740; and 3D-QSAR: r² = 0.998, q² = 0.526, and SDEP = 0.856. The molecules can be practically evaluated as superior antileishmaniasis agents.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466415","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 novel brain penetrant GSK-3β inhibitors toward Alzheimer's disease therapy by virtual screening, molecular docking, dynamic simulation, and MMPBSA analysis.","authors":"Asmita Dasgupta, Kastro Kalidass, Shabnam Farisha, Rounak Saha, Sanjukta Ghosh, Dinakara Rao Ampasala","doi":"10.1080/07391102.2024.2411524","DOIUrl":"https://doi.org/10.1080/07391102.2024.2411524","url":null,"abstract":"<p><p>One of the significant therapeutic targets for Alzheimer's disease (AD) is Glycogen Synthase Kinase-3β (GSK-3β). Inhibition of GSK-3β can prevent hyperphosphorylation of tau, and thus prevent formation and accumulation of neurofibrillary tangles and neuropil threads that block intracellular transport, trigger unfolded protein response, and increase oxidative stress, cumulatively leading to neurodegeneration. In this study, we have performed structure-based virtual screening of two small-molecule libraries from ChemDiv CNS databases using AutoDock Vina to identify hit molecules based on their binding affinities compared to that of an established GSK-3β inhibitor, indirubin-3'-monoxime (IMO). Pharmacoinformatic screening on SwissADME and pkCSM servers enabled identification of lead molecules with favorable pharmacoinformatic properties for drug likeliness, including blood brain barrier (BBB) permeability. Further, molecular dynamic simulations identified six candidate lead molecules that show stable complex formation with GSK-3β in dynamic state under physiological conditions. Principal component analysis of the dynamic state was used to plot Free Energy Landscapes (FELs) of GSK-3β-ligand complexes. STRIDE secondary structure analysis of the lowest energy conformations identified from FEL plots, and binding free energy calculations by Molecular Mechanics Poisson-Boltzmann Surface Area ((<i>ΔG_bind</i>)_MM-PBSA) of the simulation trajectories led to the identification of two ligands as potential lead molecules having favorable free energy landscape profiles as well as significantly lower (<i>ΔG_bind</i>)_MM-PBSA in dynamic state compared to that of reference inhibitor IMO. Hence, this study identifies two novel brain penetrant GSK-3β inhibitors that are likely to have therapeutic potential against Alzheimer's disease.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-27"},"PeriodicalIF":2.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466414","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":"Unveiling MurM inhibitors in <i>Enterococcus faecalis</i> V583: a promising approach to tackle antibiotic resistance.","authors":"Km Rakhi, Rittik Bhati, Monika Jain, Amit Kumar Singh, Jayaraman Muthukumaran","doi":"10.1080/07391102.2024.2415686","DOIUrl":"https://doi.org/10.1080/07391102.2024.2415686","url":null,"abstract":"<p><p><i>Enterococcus faecalis</i> is commonly found in the GI tract of humans and animals. It causes various infections, especially in hospital environments, and shows growing antibiotic resistance. This study utilized a subtractive proteomics approach to find out the potential drug targets in <i>E. faecalis</i>. Unique metabolic pathways were analysed and compared to the host to minimize adverse effects. Among twenty nine pathogenic specific and seventy three host-pathogen common pathways identified using the KEGG database, sixty seven essential proteins were found through the DEG BLAST search. PSORTB predicted that forty cytoplasmic proteins could be suitable as druggable targets. Further analysis identified fourteen proteins with virulence properties using the VFDB BLAST. Among these, seven proteins with more than ten antigenic sites were subjected to DrugBank BLAST, identifying three novel and four existing drug targets. One of the crucial drug targets, MurM, was selected due to its critical role in peptidoglycan biosynthesis. The reason for selecting MurM is crucial for addressing antibiotic resistance, disrupting bacterial cell wall synthesis, and attaining selective antimicrobial activity. MurM belongs to the mixed <i>αβ</i> class with two functional domains. The possible binding site residues of MurM are Trp31, Lys35, Trp38, Arg215, and Tyr219. Virtual screening identified potential lead candidates for MurM, and four were selected based on their physiochemical, pharmacokinetic, and structural properties. This study provides valuable insights into identifying and analysing a potential drug target, the MurM protein, and its inhibitors in <i>E. faecalis</i> V583.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466417","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}