title: Investigating the nucleic acid interactions of histone-derived antimicrobial peptides.
abstract: While many antimicrobial peptides (AMPs) disrupt bacterial membranes, some translocate into bacteria and interfere with intracellular processes. Buforin II and DesHDAP1 are thought to kill bacteria by interacting with nucleic acids. Here, molecular modeling and experimental measurements are used to show that neither nucleic acid binding peptide selectively binds DNA sequences. Simulations and experiments also show that changing lysines to arginines enhances DNA binding, suggesting that including additional guanidinium groups is a potential strategy to engineer more potent AMPs. Moreover, the lack of binding specificity may make it more difficult for bacteria to evolve resistance to these and other similar AMPs.
authors.affiliation: Department of Chemistry, Wellesley College, MA, USA.
authors.forename: Sukin
authors.initials: S
authors.lastname: Sim
authors.affiliation: Department of Chemistry, Wellesley College, MA, USA.
authors.forename: Penny
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Wellesley College, MA, USA.
authors.forename: Brittany N
authors.initials: BN
authors.lastname: Beyer
authors.affiliation: Department of Chemistry, Wellesley College, MA, USA.
authors.forename: Kara J
authors.initials: KJ
authors.lastname: Cutrona
authors.affiliation: Department of Chemistry, Wellesley College, MA, USA.|Biochemistry Program, Wellesley College, MA, USA.
authors.forename: Mala L
authors.initials: ML
authors.lastname: Radhakrishnan
authors.affiliation: Department of Chemistry, Wellesley College, MA, USA.|Biochemistry Program, Wellesley College, MA, USA.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Elmore
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D001001:Anura / Q000502:physiology; D001120:Arginine / Q000737:chemistry*; D004269:DNA, Bacterial / Q000737:chemistry*; D006657:Histones / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D007700:Kinetics; D008239:Lysine / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D018716:Molecular Mimicry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D006657:Histones; D011506:Proteins; C097849:buforin II; D001120:Arginine; D008239:Lysine
keywords: antimicrobial peptide; electrostatics calculations; molecular dynamics; nucleic acid