POSSIM: Parameterizing Complete Second-Order Polarizable Force Field for Proteins.

Area of Science:

• Computational Chemistry
• Biophysics
• Molecular Modeling

Background:

• Development of efficient and accurate computational models for molecular simulations is crucial in understanding protein behavior.
• Previous work introduced POSSIM (POlarizable Simulations with Second order Interaction Model), a fast polarizable force field and software.
• The second-order approximation in POSSIM significantly accelerates polarizable calculations.

Purpose of the Study:

• To expand the POSSIM framework by developing a complete polarizable force field specifically for proteins.
• To validate the accuracy and transferability of the new protein force field against experimental and benchmark computational data.
• To assess the suitability of the POSSIM force field for various applications, including protein-ligand complexes.

Main Methods:

• Parameter fitting primarily utilized high-level quantum mechanical data.
• Validation involved reproducing dipeptide conformational geometries and energies.
• Monte Carlo simulations were performed on collagen-like proteins and N-glycoprotein oligopeptides in water.

Main Results:

• Dipeptide conformers were reproduced with average errors of ~0.5 kcal/mol (energies) and ~9.7° (dihedral angles).
• Simulations of collagen-like proteins yielded geometries within 0.94 Å RMSD of experimental data.
• POSSIM simulations of oligopeptides showed comparable structural accuracy (within ~0.9 Å RMSD) to the OPLS-AA force field.

Conclusions:

• The developed POSSIM protein force field demonstrates high accuracy in reproducing molecular geometries and energies.
• Its performance is on par with established force fields like OPLS-AA, with improved parameter transferability and reduced complexity.
• The POSSIM force field is robust and suitable for a wide range of applications in protein and protein-ligand simulations.