biostudies-literatureCao ZDezhou University Doctoral Fund ProjectYouth Innovation Team Lead-education Project of Shandong Educational CommitteeNational Natural Science Foundation of China (NSFC)542https://www.ebi.ac.uk/biostudies/studies/S-EPMC10537873biostudies-literatureUnknown15(9)Previous experimental investigations have established the indispensability of the C-terminal Lys-Arg residues in the toxic activity of the AapA1 toxin protein. AapA1 is classified as a type I toxin-antitoxin (TA) bacterial toxin, and the precise impact of the C-terminal Lys-Arg residues on its structure and mechanism of action remains elusive. To address this knowledge gap, the present study employed molecular dynamics (MD) and enhanced sampling Well-tempered Two-dimensional Metadynamics (2D-MetaD) simulations to examine the behavior of the C-terminal Lys-Arg residues of truncated AapA1 toxin (AapA1-28) within the inner membrane of <i>Escherichia coli</i>. Specifically, the study focused on the elucidation of possible conformation states of AapA1-28 protein in POPE/POPG (3:1) bilayers and ToxinsEffects of C-Terminal Lys-Arg Residue of AapA1 Protein on Toxicity and Structural Mechanism.PMC105378732019xjrc2063217124931670727Zhao LLiu LCao ZYan TfalseEffects of C-Terminal Lys-Arg Residue of AapA1 Protein on Toxicity and Structural Mechanism.Previous experimental investigations have established the indispensability of the C-terminal Lys-Arg residues in the toxic activity of the AapA1 toxin protein. AapA1 is classified as a type I toxin-antitoxin (TA) bacterial toxin, and the precise impact of the C-terminal Lys-Arg residues on its structure and mechanism of action remains elusive. To address this knowledge gap, the present study employed molecular dynamics (MD) and enhanced sampling Well-tempered Two-dimensional Metadynamics (2D-MetaD) simulations to examine the behavior of the C-terminal Lys-Arg residues of truncated AapA1 toxin (AapA1-28) within the inner membrane of <i>Escherichia coli</i>. Specifically, the study focused on the elucidation of possible conformation states of AapA1-28 protein in POPE/POPG (3:1) bilayers and 2023-01-01T00:00:00Z2023 Sep2026-04-07T15:55:10.498Z2025-02-19T01:20:05.013ZS-EPMC105378733775596810.3390/toxins15090542