Efficient Simulation Method for Polarizable Protein Force Fields:  Application to the Simulation of BPTI in Liquid...

Area of Science:

• Computational chemistry and biophysics
• Molecular dynamics simulations
• Protein structure and dynamics

Background:

• Accurate molecular dynamics simulations require precise modeling of electrostatic interactions.
• Polarizable force fields are crucial for capturing subtle electronic effects in proteins and solvents.
• Previous methods faced challenges in computational efficiency for large-scale polarizable systems.

Purpose of the Study:

• To develop and validate a scalable methodology for molecular dynamics simulations of solvated polarizable proteins.
• To assess the computational overhead and accuracy of polarizable models compared to nonpolarizable ones.
• To simulate and analyze the structural behavior of bovine pancreatic trypsin inhibitor (BPTI) using novel polarizable potentials.

Main Methods:

• Employed a generalized P3M Ewald method for electrostatic force evaluation, incorporating point dipoles and charges.
• Utilized an extended Lagrangian formalism to propagate electrostatic configurations alongside nuclear motion.
• Performed 2 ns NVE simulations of water-solvated BPTI (20,000 atoms) using a new polarizable dipole force field and TIP4P-FQ/RPOL water models.

Main Results:

• Achieved marginal computational overhead (1.23-1.45x) per time step compared to nonpolarizable models for large systems.
• Demonstrated excellent energy conservation and stable simulation performance over 2 ns.
• Simulated BPTI structures remained within 1 Å of the experimental crystal structure, comparable to nonpolarizable OPLS-AA.

Conclusions:

• The developed methodology enables efficient and accurate large-scale molecular dynamics simulations of polarizable proteins.
• Polarizable models, when implemented with this approach, provide high fidelity structural results comparable to established nonpolarizable force fields.
• This work paves the way for more realistic simulations of protein solvation and dynamics.