Structural alignment methods

1
Structural alignment methods

• Like in sequence alignment, try to find best
  correspondence
• Look at atoms
• A 3-dimensional problem
• No a priori knowledge of equivalent positions

2
Alignment

• Structures are known for query sequences
• X-ray crystallography
• NMR spectroscopy
• Structure prediction methods
• pair wise
• multiple sequence

3
Alignment

• Output
• Superposition of atomic coordinate sets
• root mean square distance (RMSD)
• discrete Frechet distance
• Multiple protein domains possible (additional
  difficulty)

4
Alignment

• Output
• Correspondence
• implies sequence allignment
• Superposed 3-dimensional coordinates
• Used to compute
• RMSD
• PSI (percent of structural identity)
• Other scores

5
Alignment

• Usually ignore side chains
• Align backbones
• Use backbone atoms in the peptide bond
• Often only alpha carbons are used (why?)
• For highly similar structures
• Align side-chain atoms
• RMSD accounts for rotameric states

6
Algorithmic complexity

• Optimal threading sequence ? structure
• NP-complete
• (threading best alignment to members of a
  library of candidate structures)
• Optimal multiple sequence alignment
• NP-complete
• Structural alignment
• Not known

7
Algorithmic complexity

• Due to noise
• optimal solution may not be necessary
• Find approximate solutions
• heuristics
• guaranteed bounds
• Polynomial time approximation within a given
  error ? from optimal is possible
• O(n10/?6) possible