Polarization effects stabilize bacteriorhodopsin's chromophore binding pocket: a molecular dynamics study.

Area of Science:

• Computational chemistry
• Biophysics
• Spectroscopy

Background:

• Hybrid quantum mechanics/molecular mechanics (QM/MM) methods offer accurate in situ vibrational spectra.
• Accurate molecular dynamics (MD) simulations require a reliable molecular mechanics (MM) model for chromophore-protein complexes.

Purpose of the Study:

• To investigate the accuracy of MM-MD simulations for bacteriorhodopsin (BR) chromophore binding pockets.
• To address the issue of binding pocket collapse in standard MM-MD simulations.
• To explore the structural heterogeneity of the retinal chromophore binding site.

Main Methods:

• Density functional theory (DFT) and molecular mechanics (MM) hybrid computations.
• Molecular dynamics (MD) simulations using standard and polarized MM force fields.
• Hamiltonian replica exchange approach for enhanced sampling.

Main Results:

• Standard nonpolarizable MM-MD simulations lead to collapse of the BR chromophore binding pocket.
• Polarized MM force fields, derived via DFT/MM, prevent binding pocket collapse.
• MD simulations reveal significant structural heterogeneity in the BR binding pocket, particularly in the lysine chain.

Conclusions:

• Accurate MM models are crucial for reliable MD simulations of chromophore-protein systems.
• Polarized force fields are necessary to capture the correct dynamics and structure of the BR binding pocket.
• The study highlights the importance of considering protein flexibility and polarization effects in computational spectroscopy.