MUSCLE manual
Profile-profile alignment

Profile-profile alignment takes two existing MSAs ("profiles") and aligns them to each other, keeping the columns in each MSA intact. The final alignment is made by inserting columns of gaps into the MSAs as needed. The alignments of sequences in each input MSAs are thus fully preserved in the output alignment.

One or both of the input alignments may be single sequences.


  muscle -profile -in1 one.afa -in2 two.afa -out both.afa

Profile-profile alignment is not for homolog recognition
MUSCLE does not compute a similarity measure or measure of statistical significance (such as an E-value), so this option is not useful for discriminating homologs from unrelated sequences.