LifeSoaks

LifeSoaks analyzes and visualizes solvent channels in protein crystals to predict molecular accessibility and identify obstacles for soaking experiments.

Key Features:

• Voronoi diagram-based periodic channel representation: LifeSoaks uses a Voronoi diagram-based periodic channel representation which can be efficiently computed.
• Bottleneck radius calculation: The size and location of channel bottlenecks, which might hinder molecular diffusion, can be directly derived from this representation.
• Automated bottleneck annotation: LifeSoaks predicts accessibility by molecules through an automated annotation of bottleneck radii for solvent channels and small molecule binding sites.
• Large-scale database analysis: LifeSoaks provides calculated bottleneck radii for all crystal structures in the PDB and analysis of a hand-curated data set of structures obtained by soaking experiments.

Scientific Applications:

• Soaking experiment planning: LifeSoaks selects the most promising experimental conditions and crystal forms by analyzing channel accessibility before actual soaking experiments.
• Structure-based drug design: LifeSoaks evaluates whether ligands can traverse crystal solvent channels and reach corresponding binding pockets.
• Crystal packing analysis: LifeSoaks identifies whether unsuccessful screenings are attributed to the geometry of the crystal packing.
• Intracrystalline dynamics study: LifeSoaks provides knowledge of the geometry of solvent-filled channels and cavities for studying protein dynamics inside crystals.

Methodology:

LifeSoaks uses a Voronoi diagram-based periodic channel representation. The size and location of channel bottlenecks are directly derived from this representation.