From Protein Structure to Function with Bioinformatics.pdf

2 Fold Recognition 35Table 2.1 (a) BLOSUM scoring matrix (Seq)A R N D C Q F P S T W Y VA 4 −1 −2 −2 0 −1 . . −2 −1 1 0 −3 −2 0R −1 5 0 −2 −3 1 . . −3 −2 −1 −1 −3 −2 −3N −2 0 6 1 −3 0 . . −3 −2 1 0 −4 −2 −3D −2 −2 1 6 −3 0 . . −3 −1 0 −1 −4 −3 −3C 0 −3 −3 −3 9 −3 . . −2 −3 −1 −1 −2 −2 −1Q −1 1 0 0 −3 5 . . −3 −1 0 −1 −2 −1 −2. . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .F −2 −3 −3 −3 −2 −3 . . 6 −4 −2 −2 1 3 −1P −1 −2 −2 −1 −3 −1 . . −4 7 −1 −1 −4 −3 −2S 1 −1 1 0 −1 0 . . −2 −1 4 1 −3 −2 −2T 0 −1 0 −1 −1 −1 . . −2 −1 1 5 −2 −2 0W −3 −3 −4 −4 −2 −2 . . 1 −4 −3 −2 11 2 −3Y −2 −2 −2 −3 −2 −1 . . 3 −3 −2 −2 2 7 −1V 0 −3 −3 −3 −1 −2 . . −1 −2 −2 0 −3 −1 4(b) Simple secondary structure scoring matrix (SS)Predicted/known α-helix β-strand coilα-helix +1 −1 −1β-strand −1 +1 −1Coil −1 −1 +1(c) Simple solvent exposure scoring matrix (Solv)Predicted/known Buried ExposedBuried +1 −1Exposed −1 +1structure is clearly not feasible, especially when searching a database containingthousands of structures. For ordinary sequence alignment, where there are no pairwiseterms between two residues in the same protein, this alignment problem canbe solved by the recursive process of dynamic programming. However, when pairwiseterms such as knowledge-based potentials are introduced, dynamic programmingcannot be used. In conventional dynamic programming the score for aligninga residue in the sequence of interest with the candidate template structure is givenby a simple look-up table (e.g. BLOSUM or a profile/position specific scoringmatrix (PSSM); see below and Table 2.1). However, in threading, the score foraligning a residue in the sequence to a residue in the structure is determined by howall the other residues with which this site may interact have already been aligned.2.2.3 Heuristics for AlignmentBecause the threading problem is formally intractable (NP-hard), many heuristicshave been developed to attempt to sensibly sample likely alignments in the searchfor a pseudo-optimal solution in a reasonable computational time. One approach is