Hydrophobic collapse in multidomain protein folding

Area of Science:

• Biophysics
• Computational Biology
• Protein Dynamics

Background:

• Protein folding is crucial for biological function.
• Hydrophobic collapse is a key driving force in protein folding.
• The role of water in mediating protein collapse is not fully understood.

Purpose of the Study:

• To investigate the role of water molecules in the hydrophobic collapse of a two-domain protein, the BphC enzyme.
• To examine the influence of protein-water interactions on the kinetics of protein collapse.

Main Methods:

• Molecular dynamics simulations were employed.
• Simulations focused on the collapse of the BphC enzyme into a globular structure.
• Protein-water electrostatic and van der Waals forces were systematically modulated.

Main Results:

• Liquid water persists in the interdomain region at reduced density during collapse.
• Hydrophobic collapse and water depletion occur on a nanosecond timescale, slower than idealized systems.
• Disabling electrostatic forces induced dewetting and accelerated collapse; further acceleration occurred when van der Waals forces were also disabled.

Conclusions:

• Water plays a significant role in mediating and slowing down protein hydrophobic collapse.
• Protein-water interactions, particularly electrostatic forces, are critical for controlling the kinetics of collapse.
• Dewetting transitions are directly linked to accelerated protein collapse, highlighting the importance of interfacial water dynamics.