Constant-pH molecular dynamics with ionic strength effects: protonation-conformation coupling in decalysine.

Area of Science:

• Biophysics
• Computational Chemistry
• Molecular Dynamics

Background:

• Constant-pH molecular dynamics (MD) simulations are essential for studying biomolecular behavior.
• Accurately capturing protonation states and their influence on molecular conformation is critical.
• Existing methods often neglect or oversimplify the effects of ionic strength on these processes.

Purpose of the Study:

• To present a novel implementation of the stochastic titration method for constant-pH molecular dynamics.
• To incorporate ionic strength effects and improve the treatment of protonation events.
• To validate the new methodology against experimental data for a decalysine peptide.

Main Methods:

• Developed a new stochastic titration algorithm for constant-pH MD.
• Integrated ionic strength effects into the simulation framework.
• Employed a faster MD algorithm with improved handling of protonation events and force field parameterization.
• Applied the method to simulate a decalysine peptide.

Main Results:

• Achieved excellent quantitative agreement with experimental titration and helix-coil transition data for decalysine.
• Demonstrated a significant dependence of peptide behavior on ionic strength.
• Validated the accurate capture of protonation-conformation coupling and its ionic strength dependency.

Conclusions:

• The new constant-pH MD method effectively incorporates ionic strength, improving simulation accuracy.
• Including ionic strength is vital for reliable simulations of biomolecular systems.
• The methodology provides a robust tool for studying protonation-dependent conformational changes in peptides and proteins.