Solvent density and long-range dipole field around a DNA-binding protein studied by molecular dynamics

Area of Science:

• Biophysics
• Computational Biology
• Structural Biology

Background:

• Understanding protein-solvation interactions is crucial for deciphering biomolecular mechanisms.
• The 434 Cro protein is a key DNA-binding protein involved in gene regulation.

Purpose of the Study:

• To investigate the distribution and orientation of solvent molecules around the 434 Cro protein.
• To analyze the effects of protein charge state (charged vs. neutral) on solvent behavior.
• To characterize the solvent-dipole field in relation to protein surface topography.

Main Methods:

• Molecular dynamics (MD) simulations were employed using periodic-boundary conditions.
• The 434 Cro protein was simulated in both charged and neutral states.
• Local density maps and local solvent-dipole fields were analyzed to probe solvent behavior.

Main Results:

• Computed high-density solvent sites accurately mapped to experimentally determined crystal-water sites.
• Hydration shells formed around hydrophobic sidechains, while hydrophilic sidechains exhibited hydrogen-bonding sites.
• Solvent density was sensitive to protein surface concavities.
• Distinct long-range solvent-dipole field patterns were observed for charged versus neutral protein states.
• Local dipole fields differed between hydrophobic and hydrophilic sidechains.
• The charged state's dipole field showed a stronger correlation with Poisson-Boltzmann electrostatics than the neutral state.

Conclusions:

• Solvent distribution and orientation are significantly influenced by the protein's charge state and surface features.
• MD simulations provide valuable insights into protein-water interactions at the molecular level.
• The study highlights the importance of considering protein charge in solvation models.