Abstract：
:Alanine scanning is a tool in molecular biology that is commonly used to evaluate the contribution of a specific amino acid residue to the stability and function of a protein. Additionally, this tool is also used to understand whether the side chain of a specific amino acid residue plays a role in the protein's bioactivity. Furthermore, computational alanine scanning methods are utilized to predict the thermodynamic properties of proteins. These studies are utilized with the assumption that the biochemical and biophysical properties of a protein do not change with alanine scanning. Our study was dedicated to analyze the effect of alanine scanning on the biochemical and biophysical properties of intrinsically disordered proteins. To this end, we studied the impact of widely used histidine to alanine mutations in amyloid-β (Aβ). We found that the secondary and tertiary contacts, salt bridge formations, and thermodynamic properties, as well as disorder propensities and aggregation predisposition of Aβ, are impacted by the single and triple point histidine to alanine mutations. Experimental and computational studies employing the alanine scanning technique for mutating histidine to alanine in the analysis of intrinsically disordered proteins have to consider these effects.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Coskuner-Weber O,Uversky VNdoi
10.1021/acs.jcim.8b00926subject
Has Abstractpub_date
2019-02-25 00:00:00pages
871-884issue
2eissn
1549-9596issn
1549-960Xjournal_volume
59pub_type
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