Dali

Dali compares 3D protein structures to detect structural similarities and support evolutionary and functional inference by searching and aligning structures from the Protein Data Bank (PDB) and the AlphaFold Database (version 1) foldomes.

Key Features:

• Structural comparison engine: Performs 3D protein structure comparisons to identify structural similarity and produce structural alignments.
• Database of precomputed structural neighborhoods: Stores and enables browsing of precomputed structural neighborhoods derived from structural comparisons.
• Suboptimal alignment generation: Produces suboptimal alignments derived from pairwise structure comparisons to reveal alternative alignments.
• Pairwise structure comparisons: Computes pairwise structural alignments as the basis for suboptimal alignments and neighborhood calculations.
• Multiple structural alignment of conserved residues: Aligns conserved residues across multiple structural alignments to highlight conserved positions.
• Analysis of residue and ligand clustering in superimposed structures: Examines how residues and ligands cluster when structures are superimposed to infer functional conservation or shifts.
• Integration of AlphaFold Database (version 1) foldomes: Enables searching and comparison against foldomes from selected organisms in the AlphaFold Database v1.
• Annotation with protein family information: Annotates structural alignments with protein family information to aid interpretation.
• Comparison against the Protein Data Bank (PDB): Compares newly solved or modeled structures against entries stored in the PDB.

Scientific Applications:

• Evolutionary relationship discovery: Reveals evolutionary insights not discernible from sequence analysis alone by detecting structural homology.
• Functional inference: Identifies functional conservation and shifts by aligning conserved residues and examining ligand/residue clustering in superimposed structures.
• Structural database searches and annotation: Searches structural datasets including the PDB and AlphaFold DB v1 foldomes and annotates matches with protein family information.
• Protein classification and subgroup discovery: Supports discovery of novel subgroups and classification, exemplified by linking SWI/SNF, NAM, CG-1 and uncharacterized proteins to the WRKY/GCM1 clan and Gti1/Pac2.

Methodology:

Uses a structural comparison engine, a database of precomputed structural neighborhoods, generation of suboptimal alignments from pairwise structure comparisons, multiple structural alignments with conserved-residue alignment, analysis of residue and ligand clustering in superimposed structures, searching of AlphaFold Database v1 foldomes, and annotation of structural alignments with protein family information.