On the Use of EPR and sm-FRET Data to Guide the Modeling of Biomolecular Complexes

Abstract

At the moment, the macromolecular complexes having high molecular weights, containing intrinsically disordered components, interacting transiently or having membrane associated parts challenge the state-of-the-art high-resolution structural biology techniques. At the same time, the variety and coverage of the low-resolution experimental techniques, which can reveal some of the structural features of these challenging complexes, is increasing and thus boosting the development and the use of information-driven modeling approaches. Such approaches aim the translation of sparse low-resolution information into a structural model. One of the best examples of information-driven modeling approaches is the High Ambiguity DOCKing (HADDOCK). HADDOCK uses a wide range of experimental data and was so far successfully applied to the docking of various biomolecular partners. Recently, two low-resolution methods, EPR and sm-FRET were recognized by the structural biology community, since the long-range distance information derived from these methods, can be used to highlight the structural features of the challenging macromolecular complexes. Here we tested, for the first time, HADDOCK’s ability to model complexes using the EPR and sm-FRET data, and showed that with the limited amount of distance restraints acceptable solutions could be generated. Moreover, we highlighted the critical aspects that need to be taken into account when using the sm-FRET and EPR restraints in HADDOCKing. The expansion of this study to a larger number of biomolecular complexes would pave the route for including EPR and sm-FRET distance restraints in the rich repertoire of data used by HADDOCK.