{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:17:20Z","timestamp":1789139840640,"version":"build-2803163510"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Aminoglycoside acetyltransferases (AACs) catalyze the acetylation of aminoglycoside antibiotics, playing a major role in bacterial resistance and posing a serious threat to global healthcare. Despite growing interest in natural products, echinoderm-derived metabolites remain largely unexplored as AAC inhibitors. This study presents a comprehensive <jats:italic>in<\/jats:italic><jats:italic>-<\/jats:italic><jats:italic>silico<\/jats:italic> investigation into the potential of these marine compounds to inhibit four key AAC enzymes: Aminoglycoside 2\u2032-N-acetyltransferase, AAC(3)-Ib, AAC(6\u2032)-Im, and AAC(3)-Iva. A virtual screening of 1600 echinoderm metabolites was performed using molecular docking, ADMET profiling, and 100 ns molecular dynamics simulations. The top 10 compounds against each enzyme were shortlisted based on binding affinity, with CMNPD15515, CMNPD17440, CMNPD3088, and CMNPD29853 showing the most stable interactions and highest binding energies. These compounds consistently outperformed native aminoglycoside ligands in docking scores and MMGBSA binding free energy calculations, suggesting stronger inhibitory potential. While a few top hits exhibited violations of Lipinski\u2019s Rule of Five particularly in molecular weight their strong target engagement and stable dynamic profiles support their candidacy as lead molecules. This work underscores the evolutionary and structural uniqueness of echinoderm metabolites as a promising reservoir for antibiotic adjuvants. It also establishes a computational framework for prioritizing marine natural products against antibiotic resistance targets. Although experimental validation remains essential, this study provides compelling early evidence to guide future in vitro and in vivo research toward the development of novel AAC inhibitors.<\/jats:p>","DOI":"10.1371\/journal.pone.0327409","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T17:43:27Z","timestamp":1751391807000},"page":"e0327409","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["A computational study exploring echinoderm-derived compounds for inhibition of aminoglycoside acetyltransferases"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2565-6573","authenticated-orcid":true,"given":"Abdullah R.","family":"Alanzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moneerah 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Vong","year":"2012","journal-title":"Medchemcomm"},{"issue":"1","key":"pone.0327409.ref013","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1039\/C5MD00344J","article-title":"Mechanisms of resistance to aminoglycoside antibiotics: overview and perspectives","volume":"7","author":"S Garneau-Tsodikova","year":"2016","journal-title":"Medchemcomm"},{"key":"pone.0327409.ref014","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fmicb.2013.00121","article-title":"Rise and dissemination of aminoglycoside resistance: the aac(6\u2032)-Ib paradigm","volume":"4","author":"MS Ramirez","year":"2013","journal-title":"Front Microbiol"},{"issue":"5157","key":"pone.0327409.ref015","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1126\/science.8153624","article-title":"Inactivation of antibiotics and the dissemination of resistance genes","volume":"264","author":"J Davies","year":"1994","journal-title":"Science"},{"issue":"6","key":"pone.0327409.ref016","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S0966-842X(97)01033-0","article-title":"Bacterial resistance to aminoglycoside antibiotics","volume":"5","author":"J Davies","year":"1997","journal-title":"Trends Microbiol"},{"key":"pone.0327409.ref017","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev.biophys.29.1.81","article-title":"GCN5-related N-acetyltransferases: a structural overview","volume":"29","author":"F Dyda","year":"2000","journal-title":"Annu Rev Biophys Biomol Struct"},{"issue":"8","key":"pone.0327409.ref018","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1128\/AAC.45.8.2238-2244.2001","article-title":"Overexpression and characterization of the chromosomal aminoglycoside 2\u2032-N-acetyltransferase of Providencia stuartii","volume":"45","author":"K Franklin","year":"2001","journal-title":"Antimicrob Agents 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Method and assessment of docking accuracy","volume":"47","author":"RA Friesner","year":"2004","journal-title":"J Med Chem"},{"key":"pone.0327409.ref042","article-title":"Computational studies on imidazo1, 2-a pyridine-3-carboxamide analogues as antimycobacterial agents: Common pharmacophore generation, atom-based 3D-QSAR, molecular dynamics simulation, QikProp, molecular docking and prime MMGBSA approaches","volume":"5","author":"SN Mali","year":"2018","journal-title":"Open Pharmaceutical Sciences Journal"},{"key":"pone.0327409.ref043","doi-asserted-by":"crossref","unstructured":"Bowers KJ, Chow E, Xu H, Dror RO, Eastwood MP, Gregersen BA. In: Proceedings of the 2006 ACM\/IEEE Conference on Supercomputing, 2006. p. 84-es.","DOI":"10.1145\/1188455.1188544"},{"issue":"20","key":"pone.0327409.ref044","doi-asserted-by":"crossref","first-page":"10096","DOI":"10.1063\/1.1808117","article-title":"A modified TIP3P water potential for simulation with Ewald summation","volume":"121","author":"DJ Price","year":"2004","journal-title":"J Chem Phys"},{"key":"pone.0327409.ref045","doi-asserted-by":"crossref","DOI":"10.1021\/acs.jctc.7b00028","article-title":"How molecular size impacts RMSD applications in molecular dynamics simulations","volume":"13","author":"K Sargsyan","year":"2017","journal-title":"J Chem Theory Comput"},{"issue":"9","key":"pone.0327409.ref046","doi-asserted-by":"crossref","first-page":"4084","DOI":"10.1080\/07391102.2020.1852968","article-title":"Computational guided identification of novel potent inhibitors of N-terminal domain of nucleocapsid protein of severe acute respiratory syndrome coronavirus 2","volume":"40","author":"P Dhankhar","year":"2022","journal-title":"J Biomol Struct Dyn"},{"issue":"3","key":"pone.0327409.ref047","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0119264","article-title":"Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis","volume":"10","author":"L Mart\u00ednez","year":"2015","journal-title":"PLoS One"},{"issue":"5","key":"pone.0327409.ref048","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1128\/AAC.47.5.1577-1583.2003","article-title":"Aminoglycoside resistance resulting from tight drug binding to an altered aminoglycoside acetyltransferase","volume":"47","author":"S Magnet","year":"2003","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"pone.0327409.ref049","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2174\/1568005033342145","article-title":"Strategy of computer-aided drug design","volume":"3","author":"AV Veselovsky","year":"2003","journal-title":"Curr Drug Targets Infect Disord"},{"key":"pone.0327409.ref050","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/978-981-33-6191-1_9","article-title":"Computer-aided drug designing","author":"T Rajkishan","year":"2021","journal-title":"Adv Bioinformatics"},{"key":"pone.0327409.ref051","first-page":"139","article-title":"Computer-aided drug design: an innovative tool for modeling","volume":"2","author":"PP Kore","year":"2012","journal-title":"Open J Med Chem"},{"key":"pone.0327409.ref052","doi-asserted-by":"crossref","first-page":"1497668","DOI":"10.3389\/fphar.2024.1497668","article-title":"Plant and marine-derived natural products: sustainable pathways for future drug discovery and therapeutic development","volume":"15","author":"M Ahmad","year":"2025","journal-title":"Front Pharmacol"},{"issue":"9","key":"pone.0327409.ref053","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1002\/cmdc.200600155","article-title":"Prediction of ADMET properties","volume":"1","author":"U Norinder","year":"2006","journal-title":"ChemMedChem"},{"key":"pone.0327409.ref054","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3390\/ph18030297","article-title":"Prodrug approach as a strategy to enhance drug permeability","volume":"18","author":"MM de Souza","year":"2025","journal-title":"Pharmaceuticals"},{"key":"pone.0327409.ref055","article-title":"Design principles for balancing lipophilicity and permeability in beyond rule of 5 space","volume":"19","author":"H M\u00f6bitz","year":"2024","journal-title":"ChemMedChem"},{"issue":"1","key":"pone.0327409.ref056","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1021\/ci100275a","article-title":"Assessing the performance of the MM\/PBSA and MM\/GBSA methods. 1. 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