More and more evidence supports the concept that the amino acid residues engaged in functionally important interactions tend to be evolutionary conserved, i.e. the involved protein sites are coupled. This concept has been verified experimentally for many protein systems. Unfortunately, most physical scoring function-based protein design algorithms including Rosetta18 lack a term to account for the long-range site-site couplings. This may explain why it is so challenging to engineer dynamic control into proteins and design protein-protein interfaces with those physics-based approaches. In contrast, the sequence-based protein design algorithms represented by statistical coupling analysis (SCA) take the long-range site-site couplings into account but cannot filter out those sequences with energetic flaws. We are working on new algorithms to overcome the challenges in protein design by incorporating the site-site correlation information into a scoring function-based protein design scheme.