Force field impact and spin-probe modeling in molecular dynamics simulations of spin-labeled T4 lysozyme

Area of Science:

• Computational chemistry
• Biophysics
• Spectroscopy

Background:

• Accurate computation of electron paramagnetic resonance (EPR) spectra for biomolecules requires precise molecular dynamics simulations.
• Simulated trajectories must capture rapid spin-probe rotations and be sufficiently long for signal analysis, posing computational challenges.
• Evaluating force fields for conformational sampling and equilibration is essential for reliable EPR spectral calculations.

Purpose of the Study:

• To comparatively analyze the impact of different molecular dynamics (MD) force fields on conformational sampling and equilibration.
• To assess the influence of force fields on spin-probe dynamics in T4 lysozyme variants for EPR spectroscopy.
• To determine optimal simulation parameters for accurate EPR spectral computation.

Main Methods:

• Conducted molecular dynamics simulations of two spin-labeled T4 lysozyme variants (N40C and K48C).
• Utilized OPLS/AMBER and AMBER99 force fields with explicit solvent for simulation.
• Analyzed ensembles of 10x 3 ns trajectories to assess sampling convergence and equilibration.

Main Results:

• AMBER99 force field trajectories revealed subtle, site-dependent differences in spin-probe rotations and torsions more effectively.
• OPLS/AMBER force field demonstrated superior sampling and equilibration at equivalent trajectory lengths.
• Force field choice impacts the accuracy of spin-probe dynamics relevant to EPR spectroscopy.

Conclusions:

• The selection of an appropriate MD force field significantly influences the accuracy of simulated biomolecular dynamics for EPR.
• AMBER99 is advantageous for capturing fine details of spin-probe motion, while OPLS/AMBER provides better overall sampling.
• These findings aid in optimizing computational strategies for EPR spectral analysis of biomolecules.