Chemical Shift Perturbation

Reference work entry

Abstract

Chemical shift perturbation (CSP, also known as chemical shift mapping and complexation-induced changes in shift, CIS) is a common technique for demonstrating ligand binding to proteins, locating the binding site, and measuring ligand affinity. The most common application is to use changes in the 1H, 15N HSQC spectrum. In favorable cases it can be used to provide structural details of the complex. The technique is most simply applied when binding is weak (dissociation constant μM or weaker), where the dissociation rate is fast in comparison with shift changes, but can be applied with stronger binding. In the fast exchange limit, signals from regions of the protein adjacent to the ligand shift smoothly from free to bound positions during the titration. The method is simple to use and suffers from few complications, which include slower exchange, more than one binding site, multiple bound states, and protein precipitation during the titration. Some recent developments are discussed, including improving the data analysis using statistical methods and attempts to separate direct chemical shift effects of binding from indirect effects such as allosteric change.

Keywords

HSQC Affinity Allostery Statistics Protein Drug discovery Fast exchange Slow exchange Induced fit Lineshape Docking 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Molecular Biology and BiotechnologyUniversity of SheffieldSheffieldUK

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