HMM and alignment

• Profile HMMs are similar to simple sequence profiles, but in addition to the amino acid frequencies in the columns of a multiple sequence alignment they contain the position-specific probabilities for inserts and deletions along the alignment
• The logarithms of these probabilities are in fact equivalent to position-specific gap penalties (Durbin et al., 1998).

• The alignment algorithm maximizes a weighted form of coemission probability, the probability that the two HMMs will emit the same sequence of residues.
• Amino acids are weighted according to their abundance, rare coemitted amino acids contributing more to the alignment score.

• Secondary structure can be included in the HMM-HMM comparison.
• We score pairs of aligned secondary structure states in a way analogous to the classical amino acids substitution matrices.
• We use ten different substitution matrices that we derived from a statistical analysis of the structure database, one for each confidence value given by PSIPRED.