Bioinformatický seminár

Tue 11 Dec. 2012, 17:20

Title: Thomas A. Hopf et al. (2012) Three-dimensional structures of membrane proteins from genomic sequencing
Speaker: Lukáš Bača

We show that amino acid covariation in proteins, extracted from the evolutionary 
sequence record, can be used to fold transmembrane proteins. We use this
technique to predict previously unknown 3D structures for 11 transmembrane
proteins (with up to 14 helices) from their sequences alone. The prediction
method (EVfold_membrane) applies a maximum entropy approach to infer evolutionary
covariation in pairs of sequence positions within a protein family and then
generates all-atom models with the derived pairwise distance constraints. We
benchmark the approach with blinded de novo computation of known transmembrane
protein structures from 23 families, demonstrating unprecedented accuracy of the 
method for large transmembrane proteins. We show how the method can predict
oligomerization, functional sites, and conformational changes in transmembrane
proteins. With the rapid rise in large-scale sequencing, more accurate and more
comprehensive information on evolutionary constraints can be decoded from genetic
variation, greatly expanding the repertoire of transmembrane proteins amenable to
modeling by this method.