Constant pH Molecular Dynamics in Explicit Solvent with λ-Dynamics.

Area of Science:

• Biochemistry
• Computational Chemistry
• Molecular Dynamics

Background:

• Protonation state is crucial for molecular structure, dynamics, and function in condensed-phase systems.
• Traditional molecular dynamics (MD) force fields often fix protonation states, limiting environmental adaptability.
• Accurately simulating pH-dependent behavior is essential for understanding biological and chemical processes.

Purpose of the Study:

• To develop and implement a constant pH molecular dynamics simulation method in explicit solvent.
• To enable dynamic adaptation of protonation states based on the local chemical environment.
• To provide a more realistic simulation of molecular behavior across a range of pH values.

Main Methods:

• Utilized the λ-dynamics approach within the GROMACS MD package.
• Introduced a titration coordinate λ to interpolate between protonated and deprotonated states.
• Incorporated hydration free energy as a function of pH to facilitate simulations.

Main Results:

• Developed a method for constant pH molecular dynamics simulations in explicit solvent.
• Enabled dynamic changes in the protonation states of titratable groups during simulations.
• Successfully reproduced average protonation probabilities at specific pH values.

Conclusions:

• The new method allows for dynamic protonation state changes, improving simulation realism.
• This approach accurately models molecular behavior influenced by pH in solution.
• Validated the method's accuracy using titration curves of amino acids and dipeptides.