{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T05:45:20Z","timestamp":1768628720576,"version":"3.49.0"},"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"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>\n                    <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                    is a significant, multidrug-resistant pathogen that is increasingly recognized as an agent associated with hospital infections. Its increasing resistance to carbapenems and other necessary antibiotics poses a serious threat to public health worldwide. The present study provides an integrative analysis of the pan-resistome and transcriptomic landscape of carbapenem-resistant\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    (CRAB) under sub-minimum inhibitory concentrations (sub-MICs) of clinically relevant antibiotics, i.e., ciprofloxacin, amikacin sulfate, meropenem, and polymyxin B. A focused investigation was conducted into the transcriptional modulation of efflux transport systems and cellular stress-response mechanisms. To identify differentially expressed genes (DEGs) among the CRAB strains, parallel comparative RNA-Seq analysis with already available public datasets was undertaken. Concurrently, high-throughput virtual screening against the comprehensive marine natural product database (CMNPD) was done to identify inhibitors for MacB, a major ABC-type efflux transporter. Binding stability and interaction profiles of lead compounds were assessed via molecular dynamics simulations of 1000 ns. Transcriptomic profiling consistently showed increased levels of MacA-MacB efflux components, RcnB an intracellular stress-response protein LolA an outer membrane chaperone and surface antigen protein 1, especially under polymyxin B exposure. CMNPD27284 is the best candidate, having a strong binding affinity and stable interaction networks with critical MacB residues (\u22127.20 kcal\/mol). These results highlight that efflux-mediated resistance and stress adaptation are crucial factors in CRAB, and they also indicate CMNPD27284 as a potential candidate for marine-derived scaffolding in developing drugs targeting the efflux pump.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0340266","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T18:41:54Z","timestamp":1768588914000},"page":"e0340266","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative pan-resistome and transcriptomic characterization reveals differential gene expression signatures in carbapenem-resistant Acinetobacter baumannii: Insights into efflux pump regulation and therapeutic targeting strategies"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6758-443X","authenticated-orcid":true,"given":"Mohanraj","family":"Gopikrishnan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5971-8290","authenticated-orcid":true,"given":"George Priya","family":"Doss C","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"pone.0340266.ref001","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2022.1045206","article-title":"Carbapenem-resistant Acinetobacter baumannii: A challenge in the intensive care unit","volume":"13","author":"Y Jiang","year":"2022","journal-title":"Front Microbiol"},{"issue":"1","key":"pone.0340266.ref002","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13062-019-0234-0","article-title":"Genome and pan-genome analysis to classify emerging bacteria","volume":"14","author":"A Caputo","year":"2019","journal-title":"Biol Direct"},{"key":"pone.0340266.ref003","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.nmni.2015.06.005","article-title":"The bacterial pangenome as a new tool for analysing pathogenic bacteria","volume":"7","author":"L Rouli","year":"2015","journal-title":"New Microbes New Infect"},{"key":"pone.0340266.ref004","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.copbio.2019.12.001","article-title":"Current status of pan-genome analysis for pathogenic bacteria","volume":"63","author":"Y Kim","year":"2020","journal-title":"Curr Opin Biotechnol"},{"issue":"12","key":"pone.0340266.ref005","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1002\/iub.531","article-title":"The genomics of Acinetobacter baumannii: insights into genome plasticity, antimicrobial resistance and pathogenicity","volume":"63","author":"F Imperi","year":"2011","journal-title":"IUBMB Life"},{"issue":"1","key":"pone.0340266.ref006","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s13059-015-0701-6","article-title":"A novel method of consensus pan-chromosome assembly and large-scale comparative analysis reveal the highly flexible pan-genome of Acinetobacter baumannii","volume":"16","author":"AP Chan","year":"2015","journal-title":"Genome Biol"},{"issue":"11","key":"pone.0340266.ref007","first-page":"000690","article-title":"A comparative study of pan-genome methods for microbial organisms: Acinetobacter baumannii pan-genome reveals structural variation in antimicrobial resistance-carrying plasmids","volume":"7","author":"A Urhan","year":"2021","journal-title":"Microb Genom"},{"issue":"5","key":"pone.0340266.ref008","doi-asserted-by":"crossref","first-page":"596","DOI":"10.3390\/antibiotics10050596","article-title":"Pan-resistome insights into the multidrug resistance of Acinetobacter baumannii","volume":"10","author":"DLN Rodrigues","year":"2021","journal-title":"Antibiotics (Basel)"},{"key":"pone.0340266.ref009","first-page":"329","article-title":"Antimicrobial resistance and drug efflux pumps in Acinetobacter.","author":"B-D Ling","year":"2016","journal-title":"Efflux-Mediated Antimicrobial Resistance in Bacteria. Mechanisms, Regulation and Clinical Implication. Cham: Springer International Publishing"},{"key":"pone.0340266.ref010","article-title":"Acinetobacter baumannii: an evolving and cunning opponent","volume":"15","author":"J Shi","year":"2024","journal-title":"Front Microbiol"},{"issue":"10","key":"pone.0340266.ref011","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1093\/jac\/dkaf306","article-title":"Synergistic cefiderocol-containing antibiotic combinations active against highly drug-resistant Acinetobacter baumannii patient isolates with diverse resistance mechanisms","volume":"80","author":"J Halim","year":"2025","journal-title":"J Antimicrob Chemother"},{"issue":"3","key":"pone.0340266.ref012","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3390\/pathogens10030373","article-title":"Acinetobacter baumannii antibiotic resistance mechanisms","volume":"10","author":"I Kyriakidis","year":"2021","journal-title":"Pathogens"},{"key":"pone.0340266.ref013","article-title":"Pangenome-based network analysis of Acinetobacter baumannii reveals the landscape of conserved therapeutic targets","author":"T Bhat","year":"2025","journal-title":"Molecular Diversity"},{"issue":"2","key":"pone.0340266.ref014","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.02193-16","article-title":"Transcriptome remodeling of Acinetobacter baumannii during infection and treatment","volume":"8","author":"MS Wright","year":"2017","journal-title":"mBio"},{"issue":"6","key":"pone.0340266.ref015","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01660-15","article-title":"Joint transcriptional control of virulence and resistance to antibiotic and environmental stress in Acinetobacter baumannii","volume":"6","author":"MJ Gebhardt","year":"2015","journal-title":"mBio"},{"issue":"15","key":"pone.0340266.ref016","doi-asserted-by":"crossref","first-page":"5498","DOI":"10.3390\/ijms21155498","article-title":"Mechanisms protecting acinetobacter baumannii against multiple stresses triggered by the host immune response, antibiotics and outside-host environment","volume":"21","author":"S Monem","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"4","key":"pone.0340266.ref017","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1007\/s00253-019-10317-z","article-title":"Stress responses linked to antimicrobial resistance in Acinetobacter species","volume":"104","author":"B Shin","year":"2020","journal-title":"Appl Microbiol Biotechnol"},{"issue":"2","key":"pone.0340266.ref018","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1128\/CMR.00117-14","article-title":"The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria","volume":"28","author":"X-Z Li","year":"2015","journal-title":"Clin Microbiol Rev"},{"issue":"4","key":"pone.0340266.ref019","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1039\/D0MO00015A","article-title":"Pan-transcriptomic analysis identified common differentially expressed genes of Acinetobacter baumannii in response to polymyxin treatments","volume":"16","author":"M Li","year":"2020","journal-title":"Mol Omics"},{"issue":"1","key":"pone.0340266.ref020","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1038\/s41467-017-01399-2","article-title":"Crystal structure of tripartite-type ABC transporter MacB from Acinetobacter baumannii","volume":"8","author":"U Okada","year":"2017","journal-title":"Nat Commun"},{"key":"pone.0340266.ref021","article-title":"NCBI GEO: archive for functional genomics data sets--update","volume":"41","author":"T Barrett","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"pone.0340266.ref022","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkr854","article-title":"The Sequence Read Archive: explosive growth of sequencing data","volume":"40","author":"Y Kodama","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"pone.0340266.ref023","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkv1226","article-title":"Assembly: a resource for assembled genomes at NCBI","volume":"44","author":"PA Kitts","year":"2016","journal-title":"Nucleic Acids Research"},{"key":"pone.0340266.ref024","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/978-1-0716-2067-0_11","article-title":"Trimming and validation of illumina short reads using trimmomatic, trinity assembly, and assessment of RNA-Seq data","volume":"2443","author":"SO Sewe","year":"2022","journal-title":"Methods Mol Biol"},{"issue":"10","key":"pone.0340266.ref025","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkt214","article-title":"The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote","volume":"41","author":"Y Liao","year":"2013","journal-title":"Nucleic Acids Res"},{"issue":"7","key":"pone.0340266.ref026","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Y Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"pone.0340266.ref027","article-title":"Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation","volume":"44","author":"NA O\u2019Leary","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"pone.0340266.ref028","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/978-1-60327-999-4_11","article-title":"Multilocus sequence typing","volume":"551","author":"AB Ibarz Pav\u00f3n","year":"2009","journal-title":"Methods Mol Biol"},{"issue":"10","key":"pone.0340266.ref029","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/nrmicro3093","article-title":"MLST revisited: the gene-by-gene approach to bacterial genomics","volume":"11","author":"MCJ Maiden","year":"2013","journal-title":"Nat Rev Microbiol"},{"issue":"22","key":"pone.0340266.ref030","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1093\/bioinformatics\/btv421","article-title":"Roary: rapid large-scale prokaryote pan genome analysis","volume":"31","author":"AJ Page","year":"2015","journal-title":"Bioinformatics"},{"issue":"2","key":"pone.0340266.ref031","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/bioinformatics\/btx610","article-title":"Phandango: an interactive viewer for bacterial population genomics","volume":"34","author":"J Hadfield","year":"2018","journal-title":"Bioinformatics"},{"key":"pone.0340266.ref032","unstructured":"Seemann T. Tseemann\/abricate. https:\/\/github.com\/tseemann\/abricate"},{"key":"pone.0340266.ref033","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkac920","article-title":"CARD 2023: expanded curation, support for machine learning, and resistome prediction at the Comprehensive Antibiotic Resistance Database","volume":"51","author":"BP Alcock","year":"2023","journal-title":"Nucleic Acids Research"},{"key":"pone.0340266.ref034","article-title":"VFDB 2022: a general classification scheme for bacterial virulence factors","volume":"50","author":"B Liu","year":"2022","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pone.0340266.ref035","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"MD Robinson","year":"2010","journal-title":"Bioinformatics"},{"issue":"18","key":"pone.0340266.ref036","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Z Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"pone.0340266.ref037","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1471-2105-12-35","article-title":"VennDiagram: a package for the generation of highly-customizable Venn and Euler diagrams in R","volume":"12","author":"H Chen","year":"2011","journal-title":"BMC Bioinformatics"},{"issue":"5","key":"pone.0340266.ref038","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"G Yu","year":"2012","journal-title":"OMICS"},{"key":"pone.0340266.ref039","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: homology modelling of protein structures and complexes","volume":"46","author":"A Waterhouse","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"pone.0340266.ref040","doi-asserted-by":"crossref","DOI":"10.1002\/pro.4473","article-title":"PDBsum1: A standalone program for generating PDBsum analyses","volume":"31","author":"RA Laskowski","year":"2022","journal-title":"Protein Sci"},{"issue":"11","key":"pone.0340266.ref041","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1093\/bioinformatics\/18.11.1548","article-title":"Ramachandran plot on the web","volume":"18","author":"SS Sheik","year":"2002","journal-title":"Bioinformatics"},{"issue":"2","key":"pone.0340266.ref042","doi-asserted-by":"crossref","DOI":"10.1002\/wcms.1298","article-title":"Using PyMOL as a platform for computational drug design","volume":"7","author":"S Yuan","year":"2017","journal-title":"WIREs Comput Mol Sci"},{"key":"pone.0340266.ref043","article-title":"CMNPD: a comprehensive marine natural products database towards facilitating drug discovery from the ocean","volume":"49","author":"C Lyu","year":"2021","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"pone.0340266.ref044","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"O Trott","year":"2010","journal-title":"J Comput Chem"},{"issue":"1","key":"pone.0340266.ref045","doi-asserted-by":"crossref","first-page":"22","DOI":"10.24198\/ijcb.v2i1.46322","article-title":"Molecular interaction analysis and visualization of protein-ligand docking using biovia discovery studio visualizer","volume":"2","author":"SS Umi Baroroh","year":"2023","journal-title":"IJCB"},{"key":"pone.0340266.ref046","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"A Daina","year":"2017","journal-title":"Sci Rep"},{"issue":"8","key":"pone.0340266.ref047","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1021\/acs.jctc.2c01246","article-title":"CHARMM-GUI membrane builder: past, current, and future developments and applications","volume":"19","author":"S Feng","year":"2023","journal-title":"J Chem Theory Comput"},{"issue":"4","key":"pone.0340266.ref048","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/jcc.21367","article-title":"CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields","volume":"31","author":"K Vanommeslaeghe","year":"2010","journal-title":"J Comput Chem"},{"key":"pone.0340266.ref049","doi-asserted-by":"crossref","first-page":"120116","DOI":"10.1016\/j.molliq.2022.120116","article-title":"Effects of thermostats\/barostats on physical properties of liquids by molecular dynamics simulations","volume":"365","author":"Q Ke","year":"2022","journal-title":"Journal of Molecular Liquids"},{"issue":"9","key":"pone.0340266.ref050","doi-asserted-by":"crossref","first-page":"3668","DOI":"10.1063\/1.470043","article-title":"Accuracy and efficiency of the particle mesh Ewald method","volume":"103","author":"HG Petersen","year":"1995","journal-title":"J Chem Phys"},{"issue":"7","key":"pone.0340266.ref051","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/bioinformatics\/btt055","article-title":"GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit","volume":"29","author":"S Pronk","year":"2013","journal-title":"Bioinformatics"},{"issue":"12","key":"pone.0340266.ref052","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1103\/PhysRevLett.80.2733","article-title":"Vibrational dynamics of folded proteins: significance of slow and fast motions in relation to function and stability","volume":"80","author":"I Bahar","year":"1998","journal-title":"Phys Rev Lett"},{"issue":"2","key":"pone.0340266.ref053","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1021\/ct9005745","article-title":"Relation between free energy landscapes of proteins and dynamics","volume":"6","author":"GG Maisuradze","year":"2010","journal-title":"J Chem Theory Comput"},{"issue":"21","key":"pone.0340266.ref054","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1093\/bioinformatics\/btl461","article-title":"Bio3d: an R package for the comparative analysis of protein structures","volume":"22","author":"BJ Grant","year":"2006","journal-title":"Bioinformatics"},{"issue":"5","key":"pone.0340266.ref055","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"S Genheden","year":"2015","journal-title":"Expert Opin Drug Discov"},{"issue":"7","key":"pone.0340266.ref056","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1021\/ci500020m","article-title":"g_mmpbsa--a GROMACS tool for high-throughput MM-PBSA calculations","volume":"54","author":"Open Source Drug Discovery Consortium","year":"2014","journal-title":"J Chem Inf Model"},{"issue":"3","key":"pone.0340266.ref057","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1080\/07853890701195262","article-title":"Efflux pumps as antimicrobial resistance mechanisms","volume":"39","author":"K Poole","year":"2007","journal-title":"Ann Med"},{"issue":"1","key":"pone.0340266.ref058","article-title":"Synergistic inhibitory effect of polymyxin B in combination with ceftazidime against robust biofilm formed by Acinetobacter baumannii with genetic deficiency in AbaI\/AbaR quorum sensing","volume":"10","author":"Y Li","year":"2022","journal-title":"Microbiol Spectr"},{"issue":"4","key":"pone.0340266.ref059","doi-asserted-by":"crossref","first-page":"520","DOI":"10.3390\/antibiotics11040520","article-title":"Bacterial multidrug efflux pumps at the frontline of antimicrobial resistance: an overview","volume":"11","author":"L Huang","year":"2022","journal-title":"Antibiotics (Basel)"},{"issue":"7","key":"pone.0340266.ref060","article-title":"Contribution of RND superfamily multidrug efflux pumps AdeABC, AdeFGH, and AdeIJK to antimicrobial resistance and virulence factors in multidrug-resistant Acinetobacter baumannii AYE","volume":"69","author":"L Xie","year":"2025","journal-title":"Antimicrob Agents Chemother"},{"key":"pone.0340266.ref061","article-title":"Antibiotic resistance mediated by the MacB ABC transporter family: a structural and functional perspective","volume":"9","author":"NP Greene","year":"2018","journal-title":"Frontiers in Microbiology"},{"issue":"9","key":"pone.0340266.ref062","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1080\/23744235.2020.1775881","article-title":"Contribution of NDM and OXA-type carbapenemases to carbapenem resistance in clinical Acinetobacter baumannii from Nigeria","volume":"52","author":"DO Ogbolu","year":"2020","journal-title":"Infect Dis (Lond)"},{"issue":"2","key":"pone.0340266.ref063","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.str.2015.12.009","article-title":"Structural insights into outer membrane permeability of Acinetobacter baumannii","volume":"24","author":"M Zahn","year":"2016","journal-title":"Structure"},{"key":"pone.0340266.ref064","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2147\/IDR.S228089","article-title":"Acinetobacter baumannii efflux pumps and antibiotic resistance","volume":"13","author":"SN Abdi","year":"2020","journal-title":"Infect Drug Resist"},{"key":"pone.0340266.ref065","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.3389\/fmicb.2019.02519","article-title":"Bioinformatic analysis of the type VI secretion system and its potential toxins in the acinetobacter genus","volume":"10","author":"GD Repizo","year":"2019","journal-title":"Front Microbiol"},{"issue":"3","key":"pone.0340266.ref066","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s00284-022-02788-7","article-title":"Tobramycin stress induced differential gene expression in Acinetobacter baumannii","volume":"79","author":"S Kashyap","year":"2022","journal-title":"Curr Microbiol"},{"issue":"3","key":"pone.0340266.ref067","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3390\/ph18030402","article-title":"Combating antibiotic resistance: mechanisms, multidrug-resistant pathogens, and novel therapeutic approaches: an updated review","volume":"18","author":"ME Elshobary","year":"2025","journal-title":"Pharmaceuticals"},{"issue":"4","key":"pone.0340266.ref068","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s11302-019-09676-z","article-title":"Role of purines in regulation of metabolic reprogramming","volume":"15","author":"Z Tang","year":"2019","journal-title":"Purinergic Signal"},{"issue":"2","key":"pone.0340266.ref069","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.bbrc.2014.05.090","article-title":"Bacterial multidrug efflux pumps: mechanisms, physiology and pharmacological exploitations","volume":"453","author":"J Sun","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"issue":"5","key":"pone.0340266.ref070","doi-asserted-by":"crossref","first-page":"640","DOI":"10.3390\/biology12050640","article-title":"Bacterial subcellular architecture, structural epistasis, and antibiotic resistance","volume":"12","author":"F Baquero","year":"2023","journal-title":"Biology"},{"issue":"1","key":"pone.0340266.ref071","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1039\/C6ME00083E","article-title":"Insights from molecular dynamics simulations for computational protein design","volume":"2","author":"MC Childers","year":"2017","journal-title":"Mol Syst Des Eng"},{"issue":"5","key":"pone.0340266.ref072","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1021\/acs.jcim.2c01444","article-title":"Analysis of protein folding simulation with moving root mean square deviation","volume":"63","author":"Y Maruyama","year":"2023","journal-title":"J Chem Inf Model"},{"issue":"8","key":"pone.0340266.ref073","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.1073\/pnas.73.8.2740","article-title":"Thermodynamic fluctuations in protein molecules","volume":"73","author":"A Cooper","year":"1976","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pone.0340266.ref074","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1134\/S0026893308040195","article-title":"Radius of gyration as an indicator of protein structure compactness","volume":"42","author":"MYu Lobanov","year":"2008","journal-title":"Mol Biol"},{"issue":"6","key":"pone.0340266.ref075","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.str.2011.03.010","article-title":"Relative solvent accessible surface area predicts protein conformational changes upon binding","volume":"19","author":"JA Marsh","year":"2011","journal-title":"Structure"},{"issue":"1","key":"pone.0340266.ref076","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.sbi.2004.01.002","article-title":"Exploring folding free energy landscapes using computational protein design","volume":"14","author":"B Kuhlman","year":"2004","journal-title":"Curr Opin Struct Biol"},{"issue":"1","key":"pone.0340266.ref077","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1021\/acs.jctc.6b00702","article-title":"Decomposition of proteins into dynamic units from atomic cross-correlation functions","volume":"13","author":"P Calligari","year":"2017","journal-title":"J Chem Theory Comput"},{"issue":"2","key":"pone.0340266.ref078","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/minf.201100135","article-title":"Free energy calculations by the molecular mechanics poisson-boltzmann surface area method","volume":"31","author":"N Homeyer","year":"2012","journal-title":"Mol Inform"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0340266","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T18:42:10Z","timestamp":1768588930000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0340266"}},"subtitle":[],"editor":[{"given":"Feng","family":"Gao","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0340266","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]}}}