Capturing coevolutionary signals in mosaic-patterned proteins.

ROCIO ESPADA; R. GONZALO PARRA; THIERRY MORA; ALEKSANDRA M. WALCZAK; MANFRED SIPPL; DIEGO ULISES FERREIRO

York

Conferencia; Nanotechnology; 2015

Biochemichal Society

As a consequence of their inherent symmetries, repetitive, non-globular proteins are excellent models to quantitatively evaluate the relationships between sequences, structures, and biological functions of these ubiquitous macromolecular systems. We present here analytical methods to detect and compare structural repetitions in protein molecules. By an exhaustive analysis of the distribution of structural repeats using a robust metric we define those portions of a protein that best describe the overall structure as a tessellation of basic units. The patterns produced by such tessellations provide intuitive representations of the repeating regions and their association towards higher order arrangements, objectively defining the repeat-units. To capture co-evolutionary signals in and between repeat-units, we developed a simple method to perform direct coupling analysis on natural repeat-protein families, equalizing for the inherent bias introduced by the translational symmetry of the repetitions. We show that this tool can robustly identify native contacts in families of known structure and can be used to reconstruct the interactions at distances longer than repeat-pairs.