A simple general approximation for the distribution of gapped local alignment scores is presented, suitable for assessing significance of comparisons between two protein sequences or a sequence and a profile. The approximation takes account of the scoring scheme (i.e. gap penalty and substitution matrix or profile), sequence composition and length. Use of this formula means it is unnecessary to fit an extreme-value distribution to simulations or to the results of databank searches. The method is based on the theoretical ideas introduced by R. Mott and R. Tribe in 1999. Extensive simulation studies show that score-thresholds produced by the method are accurate to within +/-5 % 95 % of the time. We also investigate factors which effect the accuracy of alignment statistics, and show that any method based on asymptotic theory is limited because asymptotic behaviour is not strictly achieved for many real protein sequences, due to extreme composition effects. Consequently, it may not be practicable to find a general formula that is significantly more accurate until the sub-asymptotic behaviour of alignments is better understood.
Copyright 2000 Academic Press.