A GRID-derived water network stabilizes molecular dynamics computer simulations of a protease

Area of Science:

• Biochemistry
• Structural Biology
• Computational Chemistry

Background:

• Structural water molecules are essential for protein stability and function.
• Previous molecular dynamics (MD) studies on factor Xa highlighted the impact of water on protein flexibility.
• Limited structural data for many proteins hinders the use of multiple X-ray structures.

Purpose of the Study:

• To investigate an in silico assembled water network as an alternative to X-ray data for MD simulations.
• To assess the stability of protein structures using different water modeling approaches.
• To compare the performance of GRID-derived water networks with other methods.

Main Methods:

• Molecular dynamics (MD) simulations were performed.
• An in silico water network was generated using molecular interaction fields from the GRID program.
• Protein stability was evaluated using simulations with X-ray resolved water, GRID-derived water, and no water.

Main Results:

• MD simulations using the GRID water set demonstrated significantly improved structural stability compared to simulations without water or with only X-ray resolved water.
• The stability achieved with the GRID water set was comparable to that obtained using a water setup derived from a clustering approach.
• Neglecting crucial water molecules in initial setups led to severe structural distortions in MD simulations.

Conclusions:

• An in silico water network derived from GRID molecular interaction fields is a viable and effective alternative to using extensive X-ray data for protein MD simulations.
• This approach enhances protein structural stability in simulations, especially when limited structural data is available.
• The GRID water set method provides a robust alternative for modeling water in protein dynamics.