MSAProbs: multiple sequence alignment based on pair hidden Markov models and partition function posterior probabilities. Motivation: Multiple sequence alignment is of central importance to bioinformatics and computational biology. Although a large number of algorithms for computing a multiple sequence alignment have been designed, the efficient computation of highly accurate multiple alignments is still a challenge. Results: We present MSAProbs, a new and practical multiple alignment algorithm for protein sequences. The design of MSAProbs is based on a combination of pair hidden Markov models and partition functions to calculate posterior probabilities. Furthermore, two critical bioinformatics techniques, namely weighted probabilistic consistency transformation and weighted profile–profile alignment, are incorporated to improve alignment accuracy. Assessed using the popular benchmarks: BAliBASE, PREFAB, SABmark and OXBENCH, MSAProbs achieves statistically significant accuracy improvements over the existing top performing aligners, including ClustalW, MAFFT, MUSCLE, ProbCons and Probalign. Furthermore, MSAProbs is optimized for multi-core CPUs by employing a multi-threaded design, leading to a competitive execution time compared to other aligners. Availability: The source code of MSAProbs, written in C++, is freely and publicly available from

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