Edinburgh Research Explorer

Alpha helices are more robust to mutations than beta strands

Research output: Contribution to journalArticle

Related Edinburgh Organisations

Access status

Open

Documents

  • Download as Adobe PDF

    Final published version, 2 MB, PDF-document

    License: Creative Commons: Attribution (CC-BY)

Original languageEnglish
Article numbere1005242
JournalPLoS Computational Biology
Volume12
Issue number12
DOIs
StatePublished - 9 Dec 2016

Abstract

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.

Download statistics

No data available

ID: 29089680