Work

Free Energy Calculations of Microcin J25 Variants Binding to the FhuA Receptor

Year: 2017

Type: article

Abstract: Computer simulations were performed to study the antimicrobial peptide microcin J25 (MJ25), a 21-mer peptide with an unusual lasso structure and high activity against Gram-negative bacteria. MJ25 has intracellular targets. The initial step of MJ25 acquisition in bacterial cells is binding to the outer-membrane receptor FhuA. Molecular dynamics simulations were implemented to study the binding mechanism of MJ25 to FhuA and to search for important binding residues. The absolute binding free energy calculated from combined free energy perturbation and thermodynamic integration methods agrees well with experimental data. In addition, computational mutation analysis revealed that His5 is the key residue responsible for MJ25 and FhuA association. We found that the number of hydrogen bonds is essential for binding of MJ25 to FhuA. This atomistic, quantitative insight sheds light on the mechanism of action of MJ25 and may pave a path for designing active MJ25 analogues.

Source: Journal of Chemical Theory and Computation

DOI: 10.1021/acs.jctc.7b00417

Authors: Pin-Kuang Lai, Yiannis N. Kaznessis

Institutions: University of Minnesota, University of Minnesota System

Language: English

Topic: Antimicrobial Peptides and Activities

Subfield: Microbiology

Field: Immunology and Microbiology

Domain: Life Sciences

Open Access status: green

Funders: National Institute of General Medical Sciences, Division of Chemical, Bioengineering, Environmental, and Transport Systems

Awards: G2110183351, Lactic Acid Bacteria that Detect & Inhibit Enterococci in the Mammalian GI Tract, G4756651390