ABSTRACT
Aligning protein sequences using a score matrix has became a routine but valuable method in modern biological research. However, alignment in the ‘twilight zone’ remains an open issue. It is feasible and necessary to construct a new score matrix as more protein structures are resolved. Three structural class-specifi c score matrices (all-alpha, allbeta and alpha/beta) were constructed based on the structure alignment of low identity proteins of the corresponding structural classes. The class-specifi c score matrices were signifi cantly better than a structure-derived matrix (HSDM) and three other generalized matrices (BLOSUM30, BLOSUM60 and Gonnet250) in alignment performance tests. The optimized gap penalties presented here also promote alignment performance. The results indicate that different protein classes have distinct amino acid substitution patterns, and an amino acid score matrix should be constructed based on different structural classes. The class-specifi c score matrices could also be used in profi le construction to improve homology detection.