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PubMed · 11382360

Modeling amino acid replacement.

T Müller·M Vingron
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Abstract

The estimation of amino acid replacement frequencies during molecular evolution is crucial for many applications in sequence analysis. Score matrices for database search programs or phylogenetic analysis rely on such models of protein evolution. Pioneering work was done by Dayhoff et al. (1978) who formulated a Markov model of evolution and derived the famous PAM score matrices. Her estimation procedure for amino acid exchange frequencies is restricted to pairs of proteins that have a constant and small degree of divergence. Here we present an improved estimator, called the resolvent method, that is not subject to these limitations. This extension of Dayhoff's approach enables us to estimate an amino acid substitution model from alignments of varying degree of divergence. Extensive simulations show the capability of the new estimator to recover accurately the exchange frequencies among amino acids. Based on the SYSTERS database of aligned protein families (Krause and Vingron, 1998) we recompute a series of score matrices.

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Amino Acid SubstitutionComputer SimulationEvolution, MolecularLikelihood FunctionsMarkov ChainsModels, BiologicalProteinsStochastic ProcessesTime FactorsComparative StudyJournal Article

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T Müller, M Vingron. 2000. Modeling amino acid replacement.. https://doi.org/10.1089/10665270050514918

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