MUSCLE manual
Iterations
 
See also
 
Fastest options
  Most accurate options

  Compromise options for large datasets

The default MUSCLE algorithm is summarized in the following table. The -maxiters option can be used to choose how many of these iterations are performed, allowing a choice between higher accuracy (more iterations) and higher speed (fewer iterations). By default, MUSCLE will attempt up to 16 iterations but will terminate earlier if no changes have been made after one full refinement iteration.
 

Iteration Steps Method
1 1a. Distance matrix  k-mer counting. Can be changed by -distance1 option.
1b. Tree building UPGMB. Can be changed by -cluster1 option.
1c. Alignment Progressive alignment by tree.
 
2 1a. Distance matrix Kimura distance from MSA built in first iteration. Can be changed by ‑distance2 option.
1b. Tree building UPGMB. Can be changed by -cluster2 option.
1c. Alignment Progressive alignment by new tree.
 
3, 4, 5... Refinement The guide tree is split at every branch. A split divides the current multiple alignment into two profiles, which are re-aligned using profile-profile alignment. The new MSA is kept if the objective score is improved.