Wurst

Wurst predicts protein tertiary structures by threading amino acid sequences onto approximately 3,000 Protein Data Bank (PDB) template structures using dynamic programming and a composite scoring function.

Key Features:

• Template library: Aligns query sequences to approximately 3,000 template structures sourced from the Protein Data Bank (PDB).
• Threading-based prediction: Uses threading techniques to map sequence fragments onto structural templates for structure prediction.
• Alignment algorithm: Computes sequence-to-structure alignments using a conventional dynamic programming algorithm.
• Composite scoring function: Evaluates alignments with combined structural and sequence-based terms.
• Structural scoring: Includes structural terms represented as a log-odds probability assessing compatibility between sequence fragments and structure fragments derived from a Bayesian classification procedure.
• Sequence profiles: Applies sequence profiles to both structural and sequence-based scoring terms to incorporate evolutionary information.
• Parameter optimization: Uses simplex optimization to balance contributions from sequence and structural data.
• Alignment quality: Produces high-quality sequence-to-structure alignments for downstream model building.

Scientific Applications:

• Structural biology: Generate sequence-to-structure alignments and models to infer protein conformations for structural analysis.
• Molecular modeling: Provide template-based models useful for molecular modeling and interpretation of protein function.
• Drug discovery: Supply predicted protein conformations to support structure-based drug design and therapeutic intervention strategies.

Methodology:

Alignments are computed by a conventional dynamic programming algorithm against ~3,000 PDB templates; a scoring function combining structural and sequence-based terms (with sequence profiles) evaluates alignments, where structural terms use a log-odds probability from a Bayesian classification procedure; simplex optimization adjusts weights between sequence and structural contributions.