Disentangling direct from indirect co-evolution of residues in protein alignments.

ABSTRACT: Predicting protein structure from primary sequence is one of the ultimate challenges in computational biology. Given the large amount of available sequence data, the analysis of co-evolution, i.e., statistical dependency, between columns in multiple alignments of protein domain sequences remains one of the most promising avenues for predicting residues that are contacting in the structure. A key impediment to this approach is that strong statistical dependencies are also observed for many residue pairs that are distal in the structure. Using a comprehensive analysis of protein domains with available three-dimensional structures we show that co-evolving contacts very commonly form chains that percolate through the protein structure, inducing indirect statistical dependencies between many di

SUBMITTER: Burger L 

PROVIDER: S-EPMC2793430 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature