Structural alignment: Difference between revisions

Revision as of 19:16, 25 September 2020

Revision as of 19:20, 25 September 2020

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===Evaluating Similarity===

Often the purpose of seeking a structural superposition is not so much the superposition itself, but an evaluation of the similarity of two structures or a confidence in a remote alignment.<ref name="casp11"/><ref name="Malmstrom" /><ref name="robetta"/> A subtle but important distinction from maximal structural superposition is the conversion of an alignment to a meaningful similarity score.<ref name="Mammoth" /> ManyMost methods output some sort of "score" indicating the quality of the superposition.<ref name="zemla" /> <ref name="fischer"/> <ref name="poleksic"/><ref name="Mammoth"/><ref name="ZhangTMscore"/> However, what one actually wants is ''not'' merely an ''estimated'' "Z-score" or an ''estimated'' E-value of seeing the observed superposition by chance but instead one desires that the ''estimated'' E-value is tightly correlation to the true E-value. Critically, even if a method's estimated E-value is precisely correct ''on average'', if it lacks a low standard deviation on its estimated value generation process, then the rank ordering of the relative similarities of a query protein to a comparison set will rarely agree with the "true" ordering.<ref name="Mammoth"/><ref name="ZhangTMscore"/>

Different methods will superimpose different numbers of residues because they use different quality assurances and different definitions of "overlap"; some only include residues meeting multiple local and global superposition criteria and others are more greedy, flexible, and promiscuous. A greater number of atoms superposed can mean more similarity but it may not always produce the best E-value quantifying the unlikeliness of the superposition and thus not as useful for assessing similarity, especially in remote homologs.<ref name="casp11"/><ref name="Malmstrom" /><ref name="robetta" /><ref name="skolnick" />