Integrating Docking, Dynamics, and Assays to Predict Antimicrobial Peptide Interactions with Mycolic Acid Membranes in <i>Mycobacterium tuberculosis</i>.

ABSTRACT: The global burden of multidrug-resistant tuberculosis (MDR-TB) underscores the urgent need for novel therapeutics with distinct mechanisms of action. Here, we report a comparative evaluation of four antimicrobial peptides (AMPs) derived from the amphibian peptide B1CTcu5, integrating experimental validation with molecular modeling to elucidate structure-activity relationships. Among them, W-B1CTcu5, featuring a single N-terminal tryptophan substitution, exhibited the most potent antimycobacterial activity (MIC = 3.2 μg/mL) against Mycobacterium tuberculosis (MTB) combined with high structural stability, persistent membrane interaction, and multitarget affinity against key MTB proteins, including the porin MspA, the transporter CpnT, and the cell wall enzyme Ag85B. In contrast, analo

SUBMITTER: Roque-Borda CA 

PROVIDER: S-EPMC12715740 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature