@article {Shirian2016-qg,
	title = {Cold spots in protein binding},
	journal = {Trends Biochem. Sci.},
	volume = {41},
	number = {9},
	year = {2016},
	month = {sep},
	pages = {739{\textendash}745},
	abstract = {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 {\textquoteright}binding cold spots{\textquoteright}, 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.},
	keywords = {binding affinity, binding energetics, binding landscapes, protein-protein interactions, saturation mutagenesis},
	author = {Shirian, Jason and Sharabi, Oz and Shifman, Julia M}
}
