{"title":"Analysis of natural compounds identifies potential inhibitors for phosphoglucomutase of <i>Acinetobacter baumannii</i>: a computational approach.","authors":"Aishwarya Swain, Archana Pan","doi":"10.1007/s40203-025-00360-2","DOIUrl":null,"url":null,"abstract":"<p><p><i>Acinetobacter baumannii</i> has become resistant to almost all available antibiotics in the market, emphasizing the need to develop novel antibiotics against this pathogen. The present study aims to identify potential inhibitors for phosphoglucomutase (Pgm) of <i>A. baumannii</i> by screening natural compounds. Pgm, a key enzyme involved in bacterial cell wall biosynthesis, is identified as a promising drug target. The study first employed various computational modeling tools to predict the structure of Pgm protein as its experimental structure was unavailable. After a thorough evaluation, the AlphaFold2 model (Rank 4) was chosen and energy-minimized for molecular docking study with its natural substrates, glucose-1-phosphate (G1P) and glucose-6-phosphate (G6P). Virtual screening of the natural compounds from LOTUS and CMNPD databases against Pgm identified top five compounds DMA, DPD, 2-DPD, HAP, and DTP, which exhibited better docking scores (- 8.287 kcal/mol, - 8.082 kcal/mol, - 8.082 kcal/mol, - 8.081 kcal/mol and - 7.97 kcal/mol) compared to the natural substrates G6P and G1P (- 6.225 kcal/mol, - 5.959 kcal/mol). The drug-likeness assessment of these compounds revealed that DPD had favorable pharmacokinetic profiles and was non-carcinogenic, non-irritating to the eyes, non-corrosive, and free of respiratory toxicity, representing it as a promising drug candidate. Molecular dynamics simulations and binding free energy calculations confirmed the stable interactions of DPD with Pgm, further supporting its potential as an inhibitor. Thus, the present study elucidated a natural compound as potential inhibitor against a vital protein Pgm. Further experimental studies can be carried out to understand its antibacterial properties for developing novel drugs against <i>A. baumannii</i> infections.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-025-00360-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"13 2","pages":"76"},"PeriodicalIF":0.0000,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069764/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"In silico pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s40203-025-00360-2","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Acinetobacter baumannii has become resistant to almost all available antibiotics in the market, emphasizing the need to develop novel antibiotics against this pathogen. The present study aims to identify potential inhibitors for phosphoglucomutase (Pgm) of A. baumannii by screening natural compounds. Pgm, a key enzyme involved in bacterial cell wall biosynthesis, is identified as a promising drug target. The study first employed various computational modeling tools to predict the structure of Pgm protein as its experimental structure was unavailable. After a thorough evaluation, the AlphaFold2 model (Rank 4) was chosen and energy-minimized for molecular docking study with its natural substrates, glucose-1-phosphate (G1P) and glucose-6-phosphate (G6P). Virtual screening of the natural compounds from LOTUS and CMNPD databases against Pgm identified top five compounds DMA, DPD, 2-DPD, HAP, and DTP, which exhibited better docking scores (- 8.287 kcal/mol, - 8.082 kcal/mol, - 8.082 kcal/mol, - 8.081 kcal/mol and - 7.97 kcal/mol) compared to the natural substrates G6P and G1P (- 6.225 kcal/mol, - 5.959 kcal/mol). The drug-likeness assessment of these compounds revealed that DPD had favorable pharmacokinetic profiles and was non-carcinogenic, non-irritating to the eyes, non-corrosive, and free of respiratory toxicity, representing it as a promising drug candidate. Molecular dynamics simulations and binding free energy calculations confirmed the stable interactions of DPD with Pgm, further supporting its potential as an inhibitor. Thus, the present study elucidated a natural compound as potential inhibitor against a vital protein Pgm. Further experimental studies can be carried out to understand its antibacterial properties for developing novel drugs against A. baumannii infections.
Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00360-2.
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