Clustal-Omega is a general purpose multiple sequence alignment (MSA) program for proteins. It produces high quality MSAs and is capable of handling data-sets of hundreds of thousands of sequences in reasonable time.
In default mode, users give a file of sequences to be aligned and these are clustered to produce a guide tree and this is used to guide a "progressive alignment" of the sequences. There are also facilities for aligning existing alignments to each other, aligning a sequence to an alignment and for using a hidden Markov model (HMM) to help guide an alignment of new sequences that are homologous to the sequences used to make the HMM. This latter procedure is referred to as "external profile alignment" or EPA.
Clustal-Omega uses HMMs for the alignment engine, based on the HHalign package from Johannes Soeding . Guide trees are made by default using mBed  which can cluster very large numbers of sequences in O(N*log(N)) time. Multiple alignment then proceeds by aligning larger and larger alignments using HHalign, following the clustering given by the guide tree.
In its current form Clustal-Omega can only align protein sequences but not DNA/RNA sequences. It is envisioned that DNA/RNA will become available in a future version.
A full version of these instructions is available at http://www.clustal.org/
This is a beta version of Clustal Omega. Bugs should be reported to firstname.lastname@example.org
A standalone version of Clustal Omega for Linux/Windows/Mac is available from http://www.clustal.org/
 Johannes Soding (2005) Protein homology detection by HMM-HMM comparison. Bioinformatics 21 (7): 951–960.
 Blackshields G, Sievers F, Shi W, Wilm A, Higgins DG. Sequence embedding for fast construction of guide trees for multiple sequence alignment. Algorithms Mol Biol. 2010 May 14;5:21.