Revealing pH-dependent antimicrobial peptide, GL13K, characteristics: A constant pH molecular dynamics study

Area of Science:

• Biochemistry
• Molecular Biology
• Computational Chemistry

Background:

• Antimicrobial peptides (AMPs) offer a solution to antimicrobial resistance (AMR).
• AMPs' positive charges target negatively charged bacterial membranes.
• Low hemolytic index and non-fibril formation enhance therapeutic potential.

Purpose of the Study:

• Investigate pH-dependent behavior of the antimicrobial peptide GL13K.
• Analyze deprotonation states of lysine residues and their impact on structural dynamics.
• Understand GL13K's conformational dynamics and pKa variations.

Main Methods:

• Constant pH molecular dynamics (CpHMD) simulations.
• Analysis of lysine residue deprotonation ratios.
• Assessment of radius of gyration and end-to-end radius at varying pH.

Main Results:

• Lysine 11 (LYS11) near the C-terminus shows significant deprotonation differences.
• Increased pH leads to decreased radius of gyration and end-to-end radius.
• Random coil structures dominate in metastable states at higher pH.

Conclusions:

• GL13K exhibits pH-dependent conformational dynamics and lysine pKa variations.
• Structural insights are critical for understanding GL13K's solution behavior.
• Findings support further exploration of GL13K in multi-peptide systems for antimicrobial development.