Characterizing Protein Protonation Microstates Using Monte Carlo Sampling

Area of Science:

• Biophysics
• Computational Chemistry
• Biochemistry

Background:

• Proteins are polyelectrolytes containing acidic and basic amino acids.
• The protonation state of amino acid residues defines a protein's microstate.
• Proteins exist as an ensemble of microstates, influenced by pH and environment.

Purpose of the Study:

• To characterize protein protonation microstates using Monte Carlo simulations.
• To investigate how microstate distributions change with pH and ligand binding.
• To compare microstates in HEW lysozyme and photosynthetic reaction centers (RCs).

Main Methods:

• Monte Carlo simulations using MCCE (Master-Coupled Continuum Electrostatics).
• Analysis of protonation microstates as a function of pH.
• Calculation of thermodynamic parameters (ΔG, ΔH, ΔS) for specific residues.
• Weighted Pearson correlation analysis for residue coupling in RCs.

Main Results:

• Characterized protonation microstates in HEW lysozyme and RCs.
• Demonstrated that microstate distributions change with pH and reaction intermediates.
• Calculated thermodynamic properties for lysozyme residues with reasonable precision.
• Observed significant coupling between residue protonation states in RCs.

Conclusions:

• Protein protonation microstates are diverse and pH-dependent.
• Protonation microstates are critical for understanding protein function and reaction dynamics.
• This work provides a foundation for using microstates in molecular dynamics simulations.