Analysis of protein homology by assessing the (dis)similarity in protein loop regions

Proteins
Anna R Panchenko, Thomas Madej

Abstract

Two proteins are considered to have a similar fold if sufficiently many of their secondary structure elements are positioned similarly in space and are connected in the same order. Such a common structural scaffold may arise due to either divergent or convergent evolution. The intervening unaligned regions ("loops") between the superimposable helices and strands can exhibit a wide range of similarity and may offer clues to the structural evolution of folds. One might argue that more closely related proteins differ less in their nonconserved loop regions than distantly related proteins and, at the same time, the degree of variability in the loop regions in structurally similar but unrelated proteins is higher than in homologs. Here we introduce a new measure for structural (dis)similarity in loop regions that is based on the concept of the Hausdorff metric. This measure is used to gauge protein relatedness and is tested on a benchmark of homologous and analogous protein structures. It has been shown that the new measure can distinguish homologous from analogous proteins with the same or higher accuracy than the conventional measures that are based on comparing proteins in structurally aligned regions. We argue that this result c...Continue Reading

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Citations

Feb 18, 2010·Virus Genes·Pamela L ShawRichard Longnecker
Jun 24, 2011·Journal of Biomolecular Structure & Dynamics·Joydeep Chakraborty, Tapan K Dutta
Feb 6, 2010·BMC Bioinformatics·Leslie RegadAnne-Claude Camproux
Feb 5, 2005·BMC Evolutionary Biology·Anna R Panchenko, Thomas Madej
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Oct 3, 2008·Proteins·Saikat Chakrabarti, Anna R Panchenko
Sep 4, 2007·Archives of Biochemistry and Biophysics·Eugenia PechkovaClaudio Nicolini
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Apr 13, 2010·Journal of Molecular Biology·Kosuke HashimotoAnna R Panchenko
Sep 30, 2014·Acta Microbiologica Et Immunologica Hungarica·Saeed KhaliliJafar Amani
Oct 22, 2015·PLoS Computational Biology·Sean L SeylerOliver Beckstein
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Jul 6, 2021·Briefings in Bioinformatics·Shokouh RezaeiVuk Uskoković
Nov 9, 2018·Biochemistry·Bhanu Pratap Singh ChouhanPaola Laurino

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