CLUSTAL-W - IMPROVING THE SENSITIVITY OF PROGRESSIVE MULTIPLE SEQUENCE ALIGNMENT THROUGH SEQUENCE WEIGHTING, POSITION-SPECIFIC GAP PENALTIES AND WEIGHT MATRIX CHOICE

The sensitivity of the commonly used progressive multiple sequence ali gnment method has been greatly improved for the alignment of divergent protein sequences, Firstly, individual weights are assigned to each s equence in a partial alignment in order to down-weight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are varied at different alignment stages accordi ng to the divergence of the sequences to be aligned. Thirdly, residue- specific gap penalties and locally reduced gap penalties in hydrophili c regions encourage new gaps in potential loop regions rather than reg ular secondary structure. Fourthly, positions in early alignments wher e gaps have been opened receive locally reduced gap penalties to encou rage the opening up of new gap at these positions. These modifications are incorporated into a new program, CLUSTAL W which is freely availa ble.