Simulations of proteins in water

Area of Science:

• Biophysics
• Computational Chemistry
• Structural Biology

Background:

• Molecular dynamics (MD) simulations are crucial for understanding protein behavior.
• Simulations of hydrated protein crystals are computationally intensive and have been performed infrequently.
• Previous studies include two on pancreatic trypsin inhibitor (PTI) and one on avian pancreatic polypeptide (aPP).

Purpose of the Study:

• To assess the accuracy and reliability of molecular dynamics simulations for hydrated protein crystals.
• To analyze the energetic and structural stability of crystalline proteins in aqueous environments.
• To compare simulation results with high-resolution X-ray diffraction data.

Main Methods:

• Conducted a 40-picosecond molecular dynamics simulation of crystalline pancreatic trypsin inhibitor (PTI).
• The simulation included 4 PTI molecules, 552 water molecules, and 24 chloride ions.
• Analyzed energetic stability, interaction energy distribution, structural precision, and water/ion dynamics (diffusion, residence times).

Main Results:

• Evaluated energetic and structural stability of the hydrated protein crystal system.
• Determined the distribution of interaction energy between water, ions, and protein.
• Compared average structure and fluctuations against high-resolution (0.94-Å) X-ray data.
• Analyzed diffusional motions and residence times of water and ions within the crystal.

Conclusions:

• Molecular dynamics simulations provide valuable insights into the behavior of hydrated protein crystals.
• The study validates the reliability of MD simulations by comparing them with experimental X-ray data.
• Understanding water and ion dynamics is essential for interpreting protein crystal simulation results.