PROCAIN: Protein Profile Comparison with Assisting Information




Wang, Yong

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Detection of remote sequence homology is essential for the accurate inference of protein structure, function, and evolution. The most sensitive detection methods involve the comparison of evolutionary patterns reflected in multiple sequence alignments of protein families. We present PROCAIN, a new method for MSA comparison based on the combination of 'vertical' MSA context (substitution constraints at individual sequence positions) and 'horizontal' context (patterns of residue content at multiple positions). Based on a simple and tractable profile methodology and primitive measures for the similarity of horizontal MSA patterns, the method achieves the quality of homology detection comparable to a more complex advanced method employing hidden Markov models and secondary structure prediction. Adding secondary structure information further improves PROCAIN performance beyond the capabilities of current state-of-the-art tools. The potential value of the method for structure/function predictions is illustrated by the detection of subtle homology between evolutionary distant yet structurally similar protein domains. ProCAIn, relevant databases and tools can be downloaded from The web server can be accessed at

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