From Protein Structure to Function with Bioinformatics.pdf

2 Fold Recognition 31Fig. 2.2 Graph showing the number of experimentally-determined protein structures included inthe SCOP (Murzin et al. 1995) database together with the number of folds (as defined by SCOP)as a function of year. It can be seen that the number of structures added to SCOP is increasingrapidly, whereas the number of new folds has remained largely static since about 20042.1.4 A Note on Terminology: ‘Threading’and ‘Fold Recognition’There is often some confusion regarding the terms ‘threading’ and ‘fold recognition’.Some use the terms interchangeably, while others see threading as any techniquethat uses structural information in addition to sequence information. In thischapter I am adopting yet another position! I see fold recognition as the overarchinglabel used to describe any technique that can detect remote or tenuous connectionsbetween a sequence and a known structure. When I use the term threading(described in the next section) I am solely referring to techniques that explicitly tryto model the pairwise interactions between amino acids in a three-dimensionalstructure. This does not include the far simpler algorithms that combine 1D stringsof predicted structural features together with sequence information (which aredescribed in 3.2).2.2 ThreadingWhat are we to make of the observation that many highly dissimilar proteinsequences adopt highly similar three-dimensional structures? We have a largebody of evidence that suggests that the naturally occurring (native) state of a proteinlies in a broad and deep energy well. The protein folds to its (usually, but not