Ramachandran Outliers in Protein Conformational Switches
Korbin H. J. West, Robert Luke, Walter R. P. Novak · The FASEB Journal · 2015
Ramachandran outliers are common in proteins, and many are likely to simply be errors in the structure. However, some of these outliers will be supported by the structural data and may exist in energetically strained conformations. To date, few studies have examined the roles of Ramachandran outliers in proteins, especially with respect to functionally important backbone rearrangements. Conformational changes in the backbone of the protein may occur in response to an input signal such as ligand binding or a change in pH and are referred to as conformational switches. These conformational changes are then responsible for modifying the output of the protein such as a change in enzyme activity or in the affinity of protein-ligand, protein-protein or protein-DNA interactions. Here we present a methodology for the identification of Ramachandran outliers that may be important in conformational switching. On a subset of the Protein Data Bank containing structures of 1.5 Å resolution or better we have identified pairs of proteins in which Ramachandran outliers may be important for function. This research is supported by the Wabash College Haines Biochemistry Fund.