Antimicrobial　peptides　(AMPs)　exert　their　biological　functions　by　perturbation　with　cellular　membrane.　Conjugation　of　AMPs　with　photosensitizer　(PS)　is　a　promising　strategy　for　enhancing　the　efficacy　and　reducing　systemic　toxicity　of　AMPs.　However,　it　is　still　elusive　how　the　conjugated　PS　impacts　the　perturbation　of　AMPs　on　cell　membrane　from　molecular　level.　Here,　we　addressed　this　issue　by　a　multiscale　computational　strategy　on　pyropheophorbide-a　(PPA)　conjugated　K6L9　(PPA-K6L9),　a　PS-AMP　conjugate　developed　by　us　previously.　Our　atomistic　molecular　dynamics　(MD)　simulations　revealed　that　the　porphyrin　moiety　of　PPA　enhanced　the　stability　of　the　conjugate　in　a　lipid　bilayer　membrane　model.　Moreover,　such　moiety　also　maintained　the　amphipathic　structure　of　K6L9,　which　is　crucial　for　membrane　pore　formation.　Coarse-grained　MD　simulations　further　showed　that　the　conjugates　aggregated　in　membrane　environment　and　formed　more　stable　toroidal　pores　with　respect　to　K6L9　alone,　suggesting　the　conjugation　of　PPA　may　enhance　the　membrane-disruption　activity　of　K6L9.　Consistent　with　this,　our　cellular　experiments　confirmed　that　PPA-K6L9　was　more　toxic　to　4　T1　tumor　cells　than　K6L9.　This　study　provides　insights　into　the　mechanism　by　which　PS-AMP　conjugates　disrupt　cellular　membranes　and　could　aid　in　the　design　of　more　potent　AMP　conjugates.　©　2023　Elsevier　B.V.