CHARMM fluctuating charge force field for proteins: II protein/solvent properties from molecular dynamics simulations...

Area of Science:

• Computational chemistry
• Molecular dynamics simulations
• Protein structure analysis

Background:

• Molecular dynamics simulations are crucial for understanding protein behavior.
• Existing nonpolarizable force fields have limitations in accurately capturing subtle electronic effects.
• Polarizable force fields offer a more realistic representation of molecular interactions.

Purpose of the Study:

• To evaluate the performance of a fluctuating charge (FQ) force field for simulating small proteins.
• To assess the ability of the FQ model to reproduce native protein structures and secondary elements.
• To investigate the quantum mechanical effects and mutual polarization between protein and solvent.

Main Methods:

• Utilized fluctuating charge (FQ) force field for molecular dynamics simulations.
• Employed explicit polarizable solvent (TIP4P-FQ potential) for simulations.
• Performed constant pressure and temperature (NPT) simulations on six small proteins (1FSV, 1ENH, 1PGB, 1VII, 1H8K, 1CRN).
• Conducted gas-phase minimizations and short simulations for additional protein comparisons.

Main Results:

• The FQ force field accurately maintained protein secondary structures within 1 Å.
• Deviations from native protein structures were within 2.5 Å, comparable to nonpolarizable models.
• Observed sequence-dependent atomic charges, a quantum mechanical feature absent in nonpolarizable models.
• Demonstrated mutual polarization between protein and solvent, with increased solvent dipole moments and enhanced protein atomic charges.

Conclusions:

• The fluctuating charge force field is feasible for protein simulations.
• The FQ model captures essential quantum mechanical features and solvent-protein polarization.
• This work extends the CHARMM force field to incorporate polarizable effects for enhanced protein simulations.