Substitution matrices of residue triplets derived from protein blocks.
In protein sequence alignment, residue similarity is usually evaluated by substitution matrix, which scores all possible exchanges of one amino acid with another. Several matrices are widely used in sequence alignment, including PAM matrices derived from homologous sequence and BLOSUM matrices derived from aligned segments of BLOCKS. However, most matrices have not addressed the high-order residue-residue interactions that are vital to the bio-properties of protein. With consideration for the inherent correlation in residue triplet, we present a new scoring scheme for sequence alignment. Protein sequence is treated as overlapping and successive 3-residue segments. Two edge residues of a triplet are clustered into hydrophobic or polar categories, respectively. Protein sequence is then rewritten into triplet sequence with 2 x 20 x 2 = 80 alphabets. Using a traditional approach, we construct a new scoring scheme named TLESUM(hp) (TripLEt SUbstitution Matrices with hydrophobic and polar information) for pairwise substitution of triplets, which characterizes the similarity of residue triplets. The applications of this matrix led to marked improvements in multiple sequence alignment and in searching structurally alike residue segments. The reason for the occurrence of the "twilight zone," i.e., structure explosion of low identity sequences, is also discussed.
State Key Laboratory of Nonlinear Mechanics, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
Xin
X
Liu
Ya-Pu
YP
Zhao
D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry*; D030562:Databases, Protein; D056510:Position-Specific Scoring Matrices; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment / Q000379:methods*
D000596:Amino Acids; D011506:Proteins