{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:43:45Z","timestamp":1792784625494,"version":"4.5.0"},"reference-count":70,"publisher":"American Chemical Society (ACS)","issue":"39","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100012099","name":"Indian Institute of Technology Guwahati","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100012099","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"The Anusandhan National Research Foundation","doi-asserted-by":"publisher","award":["ANRF\/ARG\/2025\/002104\/LS"],"award-info":[{"award-number":["ANRF\/ARG\/2025\/002104\/LS"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/00d4e4338","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antimicrobial peptides (AMPs) hold immense potential in combating community-acquired and MDR infections. The therapeutic efficiency of AMPs depends on their various physicochemical properties. We investigated how the hydrophobic\u2013hydrophilic landscape of tryptophan-containing cationic heptapeptides (CAMPs) influenced their ability to bind to microbial membranes and their antimicrobial effectiveness against several ESKAPE pathogens. We found that charge delocalization over the peptide backbone enhanced antimicrobial activity, while charge localization at the C- and N-termini reduced efficacy (1.5-2.7 folds) for both the single and double tryptophan peptides. The double-tryptophan peptide P32* had increased activity over the single tryptophan peptide P32 (\u223c2.3 fold), and alleviated the effect of charge segregation on activity. Using steered molecular dynamics umbrella sampling simulations, we evaluated the peptides based on their affinity (\u0394G) for a membrane-mimetic bilayer model of Pseudomonas aeruginosa. Peptides with higher membrane-binding affinity exhibited greater antimicrobial potency. All peptides exhibited negligible hemolytic activity (HC10% \u2264 10 \u03bcM) and retained membranolytic antibacterial activity. The calculated binding free energies of the peptide(s) and the bilayer exhibited a strong linear correlation with the experimental minimum inhibitory concentration (MIC) values, with a negative slope. More favorable binding free energies (i.e., more negative values) corresponded to lower MICs, as stronger interactions with the membrane enhanced the membranolytic properties of these peptides. We demonstrated that integrating molecular simulations with experimental validation enables the use of membrane-binding free energy as a quantitative predictor of peptide activity. This approach provides a rational framework for the future design and optimization of membrane-active CAMPs.<\/jats:p>","DOI":"10.1021\/acs.jpcb.6c02992","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:02:27Z","timestamp":1789678947000},"page":"10244-10255","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Charge\nDistribution on the Membrane Binding\nand Antimicrobial Activity of Cationic Heptapeptides"],"prefix":"10.1021","volume":"130","author":[{"given":"Jyoti","family":"Gangwar","sequence":"first","affiliation":[{"name":"Indian Institute of Technology, Guwahati , , , ,","place":["Guwahati, Assam, India, 781039"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipankar","family":"Roy","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology, Guwahati , , , ,","place":["Guwahati, Assam, India, 781039"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vignesh Shanmugam","family":"Rajalakshmi","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology, Guwahati , , , ,","place":["Guwahati, Assam, India, 781039"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0391-3580","authenticated-orcid":true,"given":"Priyadarshi","family":"Satpati","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology, Guwahati , , , ,","place":["Guwahati, Assam, India, 781039"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5068-7208","authenticated-orcid":true,"given":"Sunanda","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology, Guwahati , , , ,","place":["Guwahati, Assam, India, 781039"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"2026100109061451700_cit1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2016.00194","article-title":"Antimicrobial\nPeptides: An Emerging Category of Therapeutic Agents","volume":"6","author":"Mahlapuu","year":"2016","journal-title":"Front. Cell. Infect. Microbiol."},{"issue":"1","key":"2026100109061451700_cit2","doi-asserted-by":"publisher","DOI":"10.1186\/s40779-021-00343-2","article-title":"Antimicrobial Peptides: Mechanism\nof Action, Activity and Clinical\nPotential","volume":"8","author":"Zhang","year":"2021","journal-title":"Mil. Med. Res."},{"key":"2026100109061451700_cit3","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2021.691532","article-title":"Antimicrobial\nPeptides and Proteins:\nFrom Nature\u2019s Reservoir to the Laboratory and Beyond","volume":"9","author":"Sarkar","year":"2021","journal-title":"Front. Chem."},{"issue":"7","key":"2026100109061451700_cit4","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms12071259","article-title":"Molecular Mechanisms of Bacterial\nResistance to Antimicrobial\nPeptides in the Modern Era: An Updated Review","volume":"12","author":"Tajer","year":"2024","journal-title":"Microorganisms"},{"issue":"1695","key":"2026100109061451700_cit5","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2015.0292","article-title":"Bacterial\nStrategies of Resistance\nto Antimicrobial Peptides","volume":"371","author":"Joo","year":"2016","journal-title":"Philos. Trans. R.\nSoc. London B. Biol. Sci."},{"issue":"10325","key":"2026100109061451700_cit6","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global Burden of Bacterial\nAntimicrobial Resistance in 2019: A Systematic Analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"issue":"10325","key":"2026100109061451700_cit7","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/S0140-6736(22)00087-3","article-title":"The Overlooked\nPandemic of Antimicrobial Resistance","volume":"399","author":"Laxminarayan","year":"2022","journal-title":"Lancet"},{"issue":"10322","key":"2026100109061451700_cit8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00091-5","article-title":"Antimicrobial\nResistance: Time to Repurpose the Global Fund","volume":"399","author":"The Lancet, null.","year":"2022","journal-title":"Lancet"},{"key":"2026100109061451700_cit9","doi-asserted-by":"publisher","first-page":"3813","DOI":"10.2147\/IDR.S471645","article-title":"ESKAPE Pathogens:\nAntimicrobial Resistance Patterns, Risk Factors, and Outcomes a Retrospective\nCross-Sectional Study of Hospitalized Patients in Palestine","volume":"17","author":"Abukhalil","year":"2024","journal-title":"Infect. Drug Resist."},{"issue":"3","key":"2026100109061451700_cit10","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00181-19","article-title":"Antimicrobial\nResistance in ESKAPE Pathogens","volume":"33","author":"De Oliveira","year":"2020","journal-title":"Clin. Microbiol.\nRev."},{"issue":"1","key":"2026100109061451700_cit11","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2026.2614739","article-title":"Can We Escape from Top-Priority ESKAPE\nPathogens?","volume":"15","author":"Zeng","year":"2026","journal-title":"Emerging Microbes Infect."},{"issue":"10","key":"2026100109061451700_cit12","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/s41579-024-01054-w","article-title":"ESKAPE Pathogens: Antimicrobial Resistance,\nEpidemiology,\nClinical Impact and Therapeutics","volume":"22","author":"Miller","year":"2024","journal-title":"Nat. Rev.\nMicrobiol."},{"issue":"9","key":"2026100109061451700_cit13","doi-asserted-by":"publisher","first-page":"e216","DOI":"10.1016\/S1473-3099(20)30327-3","article-title":"The Value of Antimicrobial Peptides in the Age of Resistance","volume":"20","author":"Magana","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"2026100109061451700_cit14","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1517772","article-title":"Addressing the Global\nChallenge of\nBacterial Drug Resistance: Insights, Strategies, and Future Directions","volume":"16","author":"Karnwal","year":"2025","journal-title":"Front. Microbiol."},{"issue":"7","key":"2026100109061451700_cit15","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1038\/nrmicro1441","article-title":"The Co-Evolution\nof Host Cationic Antimicrobial Peptides\nand Microbial Resistance","volume":"4","author":"Peschel","year":"2006","journal-title":"Nat. Rev. Microbiol."},{"key":"2026100109061451700_cit16","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.drup.2016.04.002","article-title":"Mechanisms and Consequences\nof Bacterial Resistance to Antimicrobial Peptides","volume":"26","author":"Andersson","year":"2016","journal-title":"Drug Resist. Updates"},{"issue":"1","key":"2026100109061451700_cit17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12364-6","article-title":"Integrated Evolutionary Analysis\nReveals Antimicrobial Peptides with Limited Resistance","volume":"10","author":"Spohn","year":"2019","journal-title":"Nat. Commun."},{"key":"2026100109061451700_cit18","doi-asserted-by":"publisher","DOI":"10.3389\/fmedt.2020.610997","article-title":"Mode-of-Action of Antimicrobial Peptides:\nMembrane\nDisruption vs. Intracellular Mechanisms","volume":"2","author":"Benfield","year":"2020","journal-title":"Front.\nMed. Technol."},{"issue":"4","key":"2026100109061451700_cit19","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02340-16","article-title":"Intracellular\nTargeting Mechanisms\nby Antimicrobial Peptides","volume":"61","author":"Le","year":"2017","journal-title":"Antimicrob. Agents\nChemother."},{"key":"2026100109061451700_cit20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1119574","article-title":"Antimicrobial Peptides\u0301 Immune Modulation Role\nin Intracellular Bacterial Infection","volume":"14","author":"Duarte-Mata","year":"2023","journal-title":"Front.\nImmunol."},{"issue":"5","key":"2026100109061451700_cit21","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics13050439","article-title":"AMPs as Host-Directed\nImmunomodulatory\nAgents against Skin Infections Caused by Opportunistic Bacterial Pathogens","volume":"13","author":"Saha","year":"2024","journal-title":"Antibiotics"},{"issue":"13","key":"2026100109061451700_cit22","doi-asserted-by":"publisher","first-page":"7820","DOI":"10.1039\/D0CS00729C","article-title":"The Multifaceted Nature of Antimicrobial Peptides:\nCurrent Synthetic Chemistry Approaches and Future Directions","volume":"50","author":"Gan","year":"2021","journal-title":"Chem. Soc. Rev."},{"issue":"6","key":"2026100109061451700_cit23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010259","article-title":"Repeated Truncation\nof a Modular Antimicrobial Peptide\nGene for Neural Context","volume":"18","author":"Hanson","year":"2022","journal-title":"PLoS Genet."},{"key":"2026100109061451700_cit24","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2026.1670569","article-title":"Hybrid and\nConjugated Antimicrobial Peptides: New Tactics to Counter Bacterial\nResistance","volume":"17","author":"Zhang","year":"2026","journal-title":"Front. Microbiol."},{"issue":"4","key":"2026100109061451700_cit25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041470","article-title":"Hybridization\nwith Insect Cecropin A (1-8) Improve the Stability\nand Selectivity of Naturally Occurring Peptides","volume":"21","author":"Yang","year":"2020","journal-title":"Int. J. Mol. Sci."},{"issue":"2","key":"2026100109061451700_cit26","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1080\/1040841X.2022.2047008","article-title":"Unnatural Amino Acids:\nPromising Implications for the Development of New Antimicrobial Peptides","volume":"49","author":"Wang","year":"2023","journal-title":"Crit. Rev. Microbiol."},{"issue":"48","key":"2026100109061451700_cit27","doi-asserted-by":"publisher","first-page":"12905","DOI":"10.1021\/acs.langmuir.6b03477","article-title":"Cyclization Improves Membrane Permeation\nby Antimicrobial\nPeptoids","volume":"32","author":"Andreev","year":"2016","journal-title":"Langmuir ACS J. Surf. Colloids"},{"issue":"6","key":"2026100109061451700_cit28","doi-asserted-by":"publisher","DOI":"10.1002\/psc.3387","article-title":"Current Synthetic Chemistry towards Cyclic Antimicrobial\nPeptides","volume":"28","author":"He","year":"2022","journal-title":"J. Pept. Sci."},{"issue":"9","key":"2026100109061451700_cit29","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12091400","article-title":"Peptide\nStapling Applied to Antimicrobial Peptides","volume":"12","author":"Lourenc\u0327o","year":"2023","journal-title":"Antibiotics"},{"issue":"9","key":"2026100109061451700_cit30","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22091430","article-title":"Advances in Development\nof Antimicrobial\nPeptidomimetics as Potential Drugs","volume":"22","author":"Molchanova","year":"2017","journal-title":"Molecules"},{"issue":"3","key":"2026100109061451700_cit31","doi-asserted-by":"publisher","first-page":"366","DOI":"10.3390\/ph8030366","article-title":"Peptides and Peptidomimetics for Antimicrobial Drug\nDesign","volume":"8","author":"Mojsoska","year":"2015","journal-title":"Pharmaceuticals"},{"issue":"7","key":"2026100109061451700_cit32","doi-asserted-by":"publisher","DOI":"10.3390\/molecules30071529","article-title":"Advances in Antimicrobial\nPeptides: Mechanisms, Design Innovations, and Biomedical Potential","volume":"30","author":"Zhang","year":"2025","journal-title":"Molecules"},{"key":"2026100109061451700_cit33","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0297-6","article-title":"Membrane Charge and\nLipid Packing Determine Polymyxin-Induced Membrane Damage","volume":"2","author":"Khondker","year":"2019","journal-title":"Commun. Biol."},{"issue":"10","key":"2026100109061451700_cit34","doi-asserted-by":"publisher","first-page":"3408","DOI":"10.1039\/D3SC04523D","article-title":"The Intricate Link\nbetween Membrane Lipid Structure\nand Composition and Membrane Structural Properties in Bacterial Membranes","volume":"15","author":"Lee","year":"2024","journal-title":"Chem. Sci."},{"key":"2026100109061451700_cit35","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.1035574","article-title":"Bacterial\nCell Membranes and Their Role in Daptomycin Resistance: A Review","volume":"9","author":"Nguyen","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"2026100109061451700_cit36","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.jtbi.2017.02.012","article-title":"Antimicrobial Potency of Cationic Antimicrobial Peptides\nCan Be Predicted from Their Amino Acid Composition: Application to\nthe Detection of \u201cCryptic\u201d Antimicrobial Peptides","volume":"419","author":"Pane","year":"2017","journal-title":"J. Theor. Biol."},{"key":"2026100109061451700_cit37","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119647","article-title":"Synthetic\nAntimicrobial Peptides: Characteristics, Design, and Potential as\nAlternative Molecules to Overcome Microbial Resistance","volume":"278","author":"Lima","year":"2021","journal-title":"Life Sci."},{"key":"2026100109061451700_cit38","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.cis.2013.06.009","article-title":"Effect of Hydrophobic\nModifications\nin Antimicrobial Peptides","volume":"205","author":"Schmidtchen","year":"2014","journal-title":"Adv. Colloid Interface\nSci."},{"issue":"10","key":"2026100109061451700_cit39","doi-asserted-by":"publisher","first-page":"2581","DOI":"10.1016\/j.bbamem.2011.06.007","article-title":"Cationic\nAmphipathic Peptides Accumulate Sialylated Proteins and Lipids in\nthe Plasma Membrane of Eukaryotic Host Cells","volume":"1808","author":"Weghuber","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"issue":"43","key":"2026100109061451700_cit40","doi-asserted-by":"publisher","first-page":"9161","DOI":"10.1021\/bi1011578","article-title":"Correlation of Charge,\nHydrophobicity, and Structure with Antimicrobial Activity of S1 and\nMIRIAM Peptides","volume":"49","author":"Leptihn","year":"2010","journal-title":"Biochemistry"},{"issue":"3","key":"2026100109061451700_cit41","doi-asserted-by":"publisher","DOI":"10.3390\/ph16030439","article-title":"Glycosylation and Lipidation\nStrategies: Approaches for Improving Antimicrobial Peptide Efficacy","volume":"16","author":"Bellavita","year":"2023","journal-title":"Pharmaceuticals"},{"issue":"19","key":"2026100109061451700_cit42","doi-asserted-by":"publisher","DOI":"10.3390\/ijms251910821","article-title":"Enhancing\nAntimicrobial Peptide Activity through Modifications of Charge, Hydrophobicity,\nand Structure","volume":"25","author":"Gagat","year":"2024","journal-title":"Int. J. Mol. Sci."},{"issue":"5","key":"2026100109061451700_cit43","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.202300451","article-title":"Optimized Charge\/Hydrophobicity\nBalance of Antimicrobial Peptides Against Polymicrobial Abdominal\nInfections","volume":"24","author":"Du","year":"2024","journal-title":"Macromol. Biosci."},{"issue":"18","key":"2026100109061451700_cit44","doi-asserted-by":"publisher","first-page":"15951","DOI":"10.1021\/acsomega.2c01089","article-title":"Delineating\nthe Mechanism of Action of a Protease Resistant\nand Salt Tolerant Synthetic Antimicrobial Peptide against Pseudomonas Aeruginosa","volume":"7","author":"Pandit","year":"2022","journal-title":"ACS\nOmega"},{"issue":"16","key":"2026100109061451700_cit45","doi-asserted-by":"publisher","first-page":"17723","DOI":"10.1021\/acs.jmedchem.5c01410","article-title":"Alchemical Simulation-Aided De Novo Design of Membrane-Active\nAntimicrobial Hepta-Peptides","volume":"68","author":"Ghosh","year":"2025","journal-title":"J. Med. Chem."},{"issue":"5","key":"2026100109061451700_cit46","doi-asserted-by":"publisher","first-page":"3941","DOI":"10.1021\/acsabm.5c00126","article-title":"Serum-Stable,\nCationic, \u03b1-Helical AMPs to Combat Infections of ESKAPE Pathogens\nand C. Albicans","volume":"8","author":"Sarkar","year":"2025","journal-title":"ACS Appl. Bio Mater."},{"issue":"1","key":"2026100109061451700_cit47","doi-asserted-by":"publisher","DOI":"10.1002\/asia.70330","article-title":"Impact of\nthe Arrangement Modes of the Antimicrobial Motifs WWR-7 and Its Analogs\nin CAMPs on Their Therapeutic Properties","volume":"21","author":"Yadav","year":"2026","journal-title":"Chem.\n\u2013 Asian J."},{"key":"2026100109061451700_cit48","unstructured":"Schro\u0308dinger, LLC.\n          . The PyMOL Molecular Graphics System2025https:\/\/pymol.org."},{"issue":"8","key":"2026100109061451700_cit49","doi-asserted-by":"publisher","first-page":"2161","DOI":"10.1021\/acs.jctc.2c01246","article-title":"CHARMM-GUI\nMembrane\nBuilder: Past, Current, and Future Developments and Applications","volume":"19","author":"Feng","year":"2023","journal-title":"J. Chem. Theory Comput."},{"issue":"4","key":"2026100109061451700_cit50","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1021\/acs.jcim.1c01514","article-title":"Comparative Molecular Dynamics Simulation\nStudies of Realistic Eukaryotic,\nProkaryotic, and Archaeal Membranes","volume":"62","author":"Pogozheva","year":"2022","journal-title":"J. Chem.\nInf. Model."},{"issue":"16","key":"2026100109061451700_cit51","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: Fast, Flexible, and Free","volume":"26","author":"Van Der Spoel","year":"2005","journal-title":"J. Comput. Chem."},{"issue":"1","key":"2026100109061451700_cit52","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m:\nAn Improved Force Field for Folded and Intrinsically Disordered Proteins","volume":"14","author":"Huang","year":"2017","journal-title":"Nat. Methods"},{"issue":"2","key":"2026100109061451700_cit53","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison\nof Simple Potential Functions for Simulating Liquid Water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"2026100109061451700_cit54","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-3-642-58360-5_2","article-title":"Steered\nMolecular Dynamics","volume-title":"Computational Molecular\nDynamics: Challenges, Methods,\nIdeas","author":"Izrailev","year":"1999"},{"issue":"5251","key":"2026100109061451700_cit55","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1126\/science.271.5251.997","article-title":"Ligand Binding: Molecular Mechanics\nCalculation of the Streptavidin-Biotin Rupture Force","volume":"271","author":"Grubmu\u0308ller","year":"1996","journal-title":"Science"},{"issue":"4","key":"2026100109061451700_cit56","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1021\/jp9110794","article-title":"Assessing the Stability\nof Alzheimer\u2019s Amyloid\nProtofibrils Using Molecular Dynamics","volume":"114","author":"Lemkul","year":"2010","journal-title":"J. Phys.\nChem. B"},{"key":"2026100109061451700_cit57","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/0021-9991(77)90121-8","article-title":"Nonphysical Sampling Distributions in Monte Carlo Free-Energy\nEstimation: Umbrella Sampling","volume":"23","author":"Torrie","year":"1977","journal-title":"J. Comput. Phys."},{"issue":"8","key":"2026100109061451700_cit58","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1002\/jcc.540130812","article-title":"THE Weighted\nHistogram Analysis Method for Free-energy Calculations on Biomolecules.\nI. The Method","volume":"13","author":"Kumar","year":"1992","journal-title":"J. Comput. Chem."},{"issue":"12","key":"2026100109061451700_cit59","doi-asserted-by":"publisher","first-page":"3713","DOI":"10.1021\/ct100494z","article-title":"G_wham\u2500A Free Weighted Histogram\nAnalysis Implementation Including Robust Error and Autocorrelation\nEstimates","volume":"6","author":"Hub","year":"2010","journal-title":"J. Chem. Theory Comput."},{"issue":"12","key":"2026100109061451700_cit60","doi-asserted-by":"publisher","first-page":"2918","DOI":"10.1046\/j.1432-1033.2002.02963.x","article-title":"Tryptophan Fluorescence\nStudy of\nthe Interaction of Penetratin Peptides with Model Membranes","volume":"269","author":"Christiaens","year":"2002","journal-title":"Eur. J. Biochem."},{"issue":"6","key":"2026100109061451700_cit61","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/s41551-021-00689-x","article-title":"Accelerated\nAntimicrobial Discovery\nvia Deep Generative Models and Molecular Dynamics Simulations","volume":"5","author":"Das","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"2026100109061451700_cit62","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/978-1-4939-2285-7_9","article-title":"In Silico Design\nof Antimicrobial Peptides","volume-title":"Computational\nPeptidology","author":"Maccari","year":"2015"},{"issue":"7","key":"2026100109061451700_cit63","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11070936","article-title":"Emerging Computational\nApproaches for Antimicrobial\nPeptide Discovery","volume":"11","author":"Agu\u0308ero-Chapin","year":"2022","journal-title":"Antibiotics"},{"key":"2026100109061451700_cit64","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiolchem.2022.107800","article-title":"Machine Learning and\nMolecular Simulation Ascertain Antimicrobial Peptide against Klebsiella Pneumoniae from Public Database","volume":"102","author":"Al-Khdhairawi","year":"2023","journal-title":"Comput. Biol. Chem."},{"issue":"4","key":"2026100109061451700_cit65","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00703-20","article-title":"Molecular\nDynamics for Antimicrobial Peptide Discovery","volume":"89","author":"Palmer","year":"2021","journal-title":"Infect. Immun."},{"issue":"1","key":"2026100109061451700_cit66","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03746-3","article-title":"In Silico Optimization of a Guava Antimicrobial Peptide\nEnables Combinatorial Exploration for Peptide Design","volume":"9","author":"Porto","year":"2018","journal-title":"Nat. Commun."},{"issue":"7","key":"2026100109061451700_cit67","doi-asserted-by":"publisher","first-page":"3172","DOI":"10.1021\/acs.jcim.1c00175","article-title":"Computational Methods\nand Tools in Antimicrobial Peptide Research","volume":"61","author":"Aronica","year":"2021","journal-title":"J. Chem. Inf. Model."},{"issue":"12","key":"2026100109061451700_cit68","doi-asserted-by":"publisher","first-page":"4839","DOI":"10.1021\/jacs.8b11939","article-title":"Simulation-Guided Rational de Novo Design of a Small Pore-Forming Antimicrobial Peptide","volume":"141","author":"Chen","year":"2019","journal-title":"J. Am. Chem. Soc."},{"issue":"28","key":"2026100109061451700_cit69","doi-asserted-by":"publisher","first-page":"5262","DOI":"10.1021\/acs.jpcb.2c01293","article-title":"Effect of Leu\/Val Mutation on the\nEnergetics of Antimicrobial Peptide:Micelle Binding","volume":"126","author":"Ghosh","year":"2022","journal-title":"J. Phys. Chem. B"},{"issue":"18","key":"2026100109061451700_cit70","doi-asserted-by":"publisher","first-page":"5823","DOI":"10.1021\/acs.jcim.3c01080","article-title":"Effect of Spacer Length Modification\nof the Cationic Side Chain on the Energetics of Antimicrobial Peptide\nBinding to Membrane-Mimetic Bilayers","volume":"63","author":"Ghosh","year":"2023","journal-title":"J. Chem.\nInf. Model."}],"container-title":["The Journal of Physical\nChemistry B"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jpcb.6c02992","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article-pdf\/130\/39\/10244\/68549038\/acs.jpcb.6c02992.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article-pdf\/130\/39\/10244\/68549038\/acs.jpcb.6c02992.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:18:19Z","timestamp":1790860699000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article\/130\/39\/10244\/5432293\/Impact-of-Charge-Distribution-on-the-Membrane"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":70,"journal-issue":{"issue":"39","published-online":{"date-parts":[[2026,9,17]]},"published-print":{"date-parts":[[2026,10,1]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jpcb.6c02992","relation":{},"ISSN":["1520-6106","1520-5207"],"issn-type":[{"value":"1520-6106","type":"print"},{"value":"1520-5207","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]}}}