Sequence alignments, variabilities, and vagaries.

It seems as if the algorithms and weighting matrices for multiple sequence alignments of the highly divergent members of the P450 gene superfamily have advanced to the point that unknown proteins can be aligned to structurally known members with reasonable accuracy. As stated earlier, the alignment tends to break down at gaps in the sequence alignments, but these regions can be improved manually. This type of alignment and analysis is especially useful for extracting and analyzing the various genome databases. Variations of the conservation analysis can be used to identify charged and uncharged residues that may be important in domain/domain interactions with redox partners or effector molecules (e.g., cytochrome b5). From these alignments and with comparative analysis within families and across P450 families, one can readily obtain an estimation of those residues that might be involved in substrate binding, in redox partner interaction, and in the catalytic mechanism.