  Studying the conformations involved in the dimerization of cadherins is
highly relevant to understand the development of tissue and its failure, which
is associated with tumors and metastases. Experimental techniques, like X-ray
crystallography, can usually report only the most stable conformations, missing
minority states that could nonetheless be important for the recognition
mechanism. Computer simulations could be a valid complement to the experimental
approach. However, standard all-atom protein models in explicit solvent are
computationally too demanding to search thoroughly the conformational space of
multiple chains composed of several hundreds of amino acids. To reach this
goal, we resorted to a coarse-grained model in implicit solvent. The standard
problem with this kind of models is to find a realistic potential to describe
their interactions. We used coevolutionary information from cadherin
alignments, corrected by a statistical potential, to build an interaction
potential which is agnostic of the experimental conformations of the protein.
Using this model, we explored the conformational space of multi-chain systems
and validated the results comparing with experimental data. We identified
dimeric conformations that are sequence-specific and that can be useful to
rationalize the mechanism of recognition between cadherins.
