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Modulating the Effect of Electrostatic Steering for Protein‐Protein Interactions via Circular Permutation
Author(s) -
Chen Xingyu,
Gao Meng,
Huang Yongqi
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.631.9
Subject(s) - barnase , electrostatics , chemistry , biophysics , molecular dynamics , crystallography , chemical physics , computational chemistry , biochemistry , biology , gene , ribonuclease , rna
Assembly of protein complexes proceeds via nonspecific encounter complexes whose formation is facilitated by long range electrostatic interactions. Mutation of charged residues and change of salt concentration are two strategies widely applied to modulate the effect of electrostatic steering. Furthermore, electrostatic interactions between two proteins may be also influenced by their conformations. Consequently, the electrostatic steering effect during binding of an unfolded protein to its target may be different from that during binding of a folded protein to its target. In this study, we employed sequence circular permutation and molecular dynamics simulations to investigate the influence of protein conformation on the encounter process. We used the well‐studied barnase/barstar complex as a model system and the coarse‐grained structure‐based Gō‐model and Debye‐Hückel function to describe interactions. Binding simulations were performed at two different temperatures such that the WT and permutated barnase were folded at the lower temperature and they were unfolded at the higher temperature. The ensembles of encounter complex and the binding rate constants were analyzed for WT barnase as well as seven permutants. Our results showed that the ensembles of encounter complex of the unfolded barnase were much diverse than those of the folded barnase. We also found that circular permutation modified the structure ensemble of unfolded barnase, resulting in difference among their ensembles of encounter complex and binding rates. Our results suggest that the protein binding process can be engineered by modulating the protein conformation ensemble. Support or Funding Information This work was supported by National Natural Science Foundation of China (Grant number: 21603121) and Hubei University of Technology. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .