Understanding the energetics and architecture of protein-binding interfaces is important for basic research and could potentially facilitate the design of novel binding domains for biotechnological applications. It is well accepted that a few key residues at binding interfaces (binding hot spots) are responsible for contributing most to the free energy of binding. In this opinion article, we introduce a new concept of ‘binding cold spots’, or interface positions occupied by suboptimal amino acids. Such positions exhibit a potential for affinity enhancement through various mutations. We give several examples of cold spots from different protein-engineering studies and argue that identification of such positions is crucial for studies of protein evolution and protein design.
Bibliographical noteFunding Information:
We thank Gideon Schreiber for reading of the manuscript. This research was supported by the Israel Science Foundation grant 1873/15.
© 2016 Elsevier Ltd
- binding affinity
- binding energetics
- binding landscapes
- protein–protein interactions
- saturation mutagenesis