Titratable Martini model for constant pH simulations.

Area of Science:

• Computational chemistry
• Molecular modeling
• Biophysics

Background:

• Classical coarse-grained (CG) molecular dynamics simulations lack accurate pH effect modeling.
• Accurate pH representation is crucial for simulating biological and chemical systems.

Purpose of the Study:

• To develop and validate a novel, fast method for including pH effects in CG molecular dynamics simulations.
• To enhance the capabilities of the Martini CG model for pH-dependent phenomena.

Main Methods:

• Modification of the Martini CG model by adding explicit proton mimicking particles.
• Validation against experimental data for titration curves, free energies of transfer, and membrane affinities.
• Application to oleic acid for studying passive translocation and to a dendrimer for collective titratable site interactions.

Main Results:

• The method accurately reproduces experimental data across various molecules and conditions.
• Qualitative reproduction of oleic acid translocation and dendrimer expansion/pKa shifts.
• Demonstrated ability to capture collective interactions in large molecules with multiple titratable sites.

Conclusions:

• The developed method provides a computationally efficient way to simulate pH-dependent processes in CG molecular dynamics.
• This approach significantly expands the applicability of CG simulations in chemistry and biology.
• The model shows promise for studying complex systems with numerous titratable groups.