WatAA

WatAA maps the ordered first hydration shell around amino acid residues by integrating analyses of 2,818 high-resolution protein crystal structures (resolution better than 1.8 Å) with ab initio quantum mechanics calculations to characterize water positions, preferred hydration sites, hydrogen placements, interaction types, and stabilizing energies.

Key Features:

• Comprehensive data source: Analyzes the first hydration shell for all 20 standard amino acids using a nonredundant set of 2,818 protein crystal structures (resolution better than 1.8 Å) while accounting for residue conformation, secondary structure, and solvent accessibility.
• Density distribution and preferred hydration sites: Identifies preferred hydration sites as maxima in pseudo-electron-density representations derived from compiled water density distributions around individual residues, indicating interactions with main-chain and side-chain atoms.
• Diverse interaction types: Reports noncanonical hydration interactions including carbon-donor hydrogen bonds, OH-π interactions, and off-plane interactions with aromatic heteroatoms.
• Experimental and computational integration: Integrates experimental crystallographic data with ab initio quantum mechanics calculations that optimize water positions at hydration sites, determine hydrogen-atom placements, and quantify interaction energies stabilizing water molecules.

Scientific Applications:

• Crystallographic refinement: Validates and guides water placement within electron density maps during crystallographic refinement.
• Drug design: Identifies water molecules mediating protein–ligand interactions to inform rational drug design and analyses of molecular recognition.
• Molecular dynamics simulations: Supports setup and evaluation of molecular dynamics simulations by providing detailed hydration site information.
• Protein structure prediction: Provides experimentally-derived and energetically-optimized hydration data to inform modeling of solvent effects in structure prediction.

Methodology:

Data mining of a nonredundant set of 2,818 protein crystal structures (resolution better than 1.8 Å) to compile water density distributions and pseudo-electron-density maps for identification of hydration-site maxima, followed by ab initio quantum mechanics calculations to optimize water positions, determine hydrogen-atom placements, and quantify interaction energies.