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This review provides an overview on the development of Multiple sequence alignment (MSA) methods and their main applications. It is focused on progress made over the past decade. The three first sections review recent algorithmic developments for protein, RNA/DNA and genomic alignments. The fourth section deals with benchmarks and explores the relationship between empirical and simulated data, along with the impact on method developments. The last part of the review gives an overview on available MSA local reliability estimators and their dependence on various algorithmic properties of available methods., (© The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

The PSI/TM-Coffee web server performs multiple sequence alignment (MSA) of proteins by combining homology extension with a consistency based alignment approach. Homology extension is performed with Position Specific Iterative (PSI) BLAST searches against a choice of redundant and non-redundant databases. The main novelty of this server is to allow databases of reduced complexity to rapidly perform homology extension. This server also gives the possibility to use transmembrane proteins (TMPs) reference databases to allow even faster homology extension on this important category of proteins. Aside from an MSA, the server also outputs topological prediction of TMPs using the HMMTOP algorithm. Previous benchmarking of the method has shown this approach outperforms the most accurate alignment methods such as MSAProbs, Kalign, PROMALS, MAFFT, ProbCons and PRALINE™. The web server is available at http://tcoffee.crg.cat/tmcoffee., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

This article introduces the T-RMSD web server (tree-based on root-mean-square deviation), a service allowing the online computation of structure-based protein classification. It has been developed to address the relation between structural and functional similarity in proteins, and it allows a fine-grained structural clustering of a given protein family or group of structurally related proteins using distance RMSD (dRMSD) variations. These distances are computed between all pairs of equivalent residues, as defined by the ungapped columns within a given multiple sequence alignment. Using these generated distance matrices (one per equivalent position), T-RMSD produces a structural tree with support values for each cluster node, reminiscent of bootstrap values. These values, associated with the tree topology, allow a quantitative estimate of structural distances between proteins or group of proteins defined by the tree topology. The clusters thus defined have been shown to be structurally and functionally informative. The T-RMSD web server is a free website open to all users and available at http://tcoffee.crg.cat/apps/tcoffee/do:trmsd.