Evolutionary Stability of Salt Bridges Hints Its Contribution to Stability of Proteins

Xiaofeng Ban, Pratik Lahiri, Abhishek S. Dhoble, Dan Li, Zhengbiao Gu, Caiming Li, Li Cheng, Yan Hong, Zhaofeng Li, Bhalerao Kaustubh

Research output: Contribution to journalArticlepeer-review


The contribution of newly designed salt bridges to protein stabilization remains controversial even today. In order to solve this problem, we investigated salt bridges from two aspects: spatial distribution and evolutionary characteristics of salt bridges. Firstly, we analyzed spatial distribution of salt bridges in proteins, elucidating the basic requirements of forming salt bridges. Then, from an evolutionary point of view, the evolutionary characteristics of salt bridges as well as their neighboring residues were investigated in our study. The results demonstrate that charged residues appear more frequently than other neutral residues at certain positions of sequence even under evolutionary pressure, which are able to form electrostatic interactions that could increase the evolutionary stability of corresponding amino acid regions, enhancing their importance to stability of proteins. As a corollary, we conjectured that the newly designed salt bridges with more contribution to proteins, not only, are qualified spatial distribution of salt bridges, but also, are needed to further increase the evolutionary stability of corresponding amino acid regions. Based on analysis, the 8 mutations were accordingly constructed in the 1,4-α-glucan branching enzyme (EC, GBE) from Geobacillus thermoglucosidans STB02, of which 7 mutations improved thermostability of GBE. The enhanced thermostability of 7 mutations might be a result of additional salt bridges on residue positions that at least one of amino acids positions is conservative, improving their contribution of stabilization to proteins.

Original languageEnglish (US)
Pages (from-to)895-903
Number of pages9
JournalComputational and Structural Biotechnology Journal
StatePublished - 2019


  • Evolutionary stability
  • Evolutionary trace
  • Mutagenesis
  • Salt bridge
  • Thermostability

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Computer Science Applications


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