title: Cold Spots in Protein Binding.
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 '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.
authors.affiliation: Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Jason
authors.initials: J
authors.lastname: Shirian
authors.affiliation: Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Oz
authors.initials: O
authors.lastname: Sharabi
authors.affiliation: Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. Electronic address: jshifman@mail.huji.ac.il.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Shifman
mesh_terms: D006801:Humans; D011485:Protein Binding; D015202:Protein Engineering; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D011506:Proteins
keywords: binding affinity; binding energetics; binding landscapes; protein–protein interactions; saturation mutagenesis