Alpha Helices Are More Robust to Mutations than Beta Strands.

The rapidly increasing amount of data on human genetic variation has resulted in a growing demand to identify pathogenic mutations computationally, as their experimental validation is currently beyond reach. Here we show that alpha helices and beta strands differ significantly in their ability to to...

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Main Authors: György Abrusán, Joseph A Marsh
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-12-01
Series:PLoS Computational Biology
Online Access:http://europepmc.org/articles/PMC5147804?pdf=render
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spelling doaj-9300dc05e4d844b68a5a13e60313ecd22020-11-25T01:44:39ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582016-12-011212e100524210.1371/journal.pcbi.1005242Alpha Helices Are More Robust to Mutations than Beta Strands.György AbrusánJoseph A MarshThe rapidly increasing amount of data on human genetic variation has resulted in a growing demand to identify pathogenic mutations computationally, as their experimental validation is currently beyond reach. Here we show that alpha helices and beta strands differ significantly in their ability to tolerate mutations: helices can accumulate more mutations than strands without change, due to the higher numbers of inter-residue contacts in helices. This results in two patterns: a) the same number of mutations causes less structural change in helices than in strands; b) helices diverge more rapidly in sequence than strands within the same domains. Additionally, both helices and strands are significantly more robust than coils. Based on this observation we show that human missense mutations that change secondary structure are more likely to be pathogenic than those that do not. Moreover, inclusion of predicted secondary structure changes shows significant utility for improving upon state-of-the-art pathogenicity predictions.http://europepmc.org/articles/PMC5147804?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author György Abrusán
Joseph A Marsh
spellingShingle György Abrusán
Joseph A Marsh
Alpha Helices Are More Robust to Mutations than Beta Strands.
PLoS Computational Biology
author_facet György Abrusán
Joseph A Marsh
author_sort György Abrusán
title Alpha Helices Are More Robust to Mutations than Beta Strands.
title_short Alpha Helices Are More Robust to Mutations than Beta Strands.
title_full Alpha Helices Are More Robust to Mutations than Beta Strands.
title_fullStr Alpha Helices Are More Robust to Mutations than Beta Strands.
title_full_unstemmed Alpha Helices Are More Robust to Mutations than Beta Strands.
title_sort alpha helices are more robust to mutations than beta strands.
publisher Public Library of Science (PLoS)
series PLoS Computational Biology
issn 1553-734X
1553-7358
publishDate 2016-12-01
description The rapidly increasing amount of data on human genetic variation has resulted in a growing demand to identify pathogenic mutations computationally, as their experimental validation is currently beyond reach. Here we show that alpha helices and beta strands differ significantly in their ability to tolerate mutations: helices can accumulate more mutations than strands without change, due to the higher numbers of inter-residue contacts in helices. This results in two patterns: a) the same number of mutations causes less structural change in helices than in strands; b) helices diverge more rapidly in sequence than strands within the same domains. Additionally, both helices and strands are significantly more robust than coils. Based on this observation we show that human missense mutations that change secondary structure are more likely to be pathogenic than those that do not. Moreover, inclusion of predicted secondary structure changes shows significant utility for improving upon state-of-the-art pathogenicity predictions.
url http://europepmc.org/articles/PMC5147804?pdf=render
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AT josephamarsh alphahelicesaremorerobusttomutationsthanbetastrands
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