Constant pH Simulation with FMM Electrostatics in GROMACS. (B) GPU Accelerated Hamiltonian Interpolation

Area of Science:

• Computational chemistry and biophysics
• Molecular dynamics simulations
• Biomolecular modeling

Background:

• Protonation states of titratable groups in biomolecules critically affect their structure and function.
• Standard molecular dynamics (MD) simulations often neglect the dynamic coupling between protonation states and biomolecular conformations.
• Simulating systems at constant pH requires specialized methods that are computationally expensive.

Purpose of the Study:

• To introduce a rigorous and efficient method for performing constant pH molecular dynamics simulations.
• To overcome the computational limitations of existing Hamiltonian Interpolation (HI) λ-dynamics methods, particularly with Particle Mesh Ewald (PME).
• To enable accurate and efficient simulation of protonation dynamics in large biomolecular systems.

Main Methods:

• Development of the Multipole-Accelerated Hamiltonian Interpolation (MAHI) method within the GROMACS simulation package.
• Utilizing precomputed charge-scaled Hamiltonians with the Fast Multipole Method (FMM) for efficient force calculation.
• Comparison of MAHI with charge interpolation (QI) and standard HI methods.

Main Results:

• MAHI achieves accurate constant pH simulations with negligible computational overhead compared to standard FMM-based MD.
• Hamiltonian Interpolation (HI) demonstrates more frequent protonation state transitions, leading to improved sampling and accuracy over charge interpolation (QI).
• Simulations with up to 512 titratable sites on a million-atom system showed less than a 20% increase in runtime.

Conclusions:

• MAHI provides a computationally feasible approach for large-scale constant pH molecular dynamics simulations.
• The method facilitates seamless integration of constant pH simulations into standard force field workflows.
• This advancement enables more accurate investigations into the pH-dependent behavior of biological macromolecules.