Internal cavities and buried waters in globular proteins

Area of Science:

• Structural Biology
• Computational Biology
• Biophysics

Background:

• Proteins often contain internal cavities.
• The role and occupancy of these cavities, particularly by water molecules, remain areas of interest.
• Understanding internal protein structure is crucial for drug design and protein function prediction.

Purpose of the Study:

• To develop and validate a fast algorithm for detecting internal protein cavities.
• To predict the locations of buried water molecules within these cavities.
• To characterize cavities by volume, surface area, polarity, and water content.

Main Methods:

• A novel computational algorithm was developed for cavity detection.
• The algorithm analyzes protein structures to identify and quantify internal voids.
• Cavity properties (volume, surface area, polarity) were assessed, and water occupancy was predicted.

Main Results:

• The algorithm successfully predicted over 80% of internal water molecule locations in 12 high-resolution protein structures.
• Most proteins analyzed possess internal cavities ranging from 10 to 180 A3.
• Cavity size positively correlates with the probability of containing buried water, though many large cavities were found to be empty.

Conclusions:

• Internal protein cavities are common structural features.
• Cavity size is a significant factor in determining water molecule occupancy.
• The algorithm provides a valuable tool for analyzing protein internal structure and water dynamics, with implications for protein energetics and function.