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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2016-12-01
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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 |
work_keys_str_mv |
AT gyorgyabrusan alphahelicesaremorerobusttomutationsthanbetastrands AT josephamarsh alphahelicesaremorerobusttomutationsthanbetastrands |
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