The use of brominated fragments for X-ray screening is well known; it was the basis for former company SGX (now part of Lilly). The purported advantage of brominated fragment is that you can identify the fragment unambiguously using anomolous dispersion. In this paper, they are focused on using fragments to identify surface binding sites on HIV protease. Prior work has focused on creating a new crystal form (complexed with TL-3, a known active site inhibitor) that has four solvent accesible sites: the exosite, the flap, and the two previous identified sites. They took 68 brominated fragments and soaked these crystals: 23 fragments were found. However, most of these actives were uninteresting. Two compounds were found to be interesting, one bound in the exosite and one in the flap site.
So, what's interesting in this paper? Well, they (re)discover that brominated fragments can bind all over with a variety of affinities. However, the bromine allows you to unambiguously identify those fragments through anomolous dispersion. This is NOT interesting. They discover that although it is a subject of much debate lately: specific interactions of the ligand with the target dominate the "bromine interaction". This IS interesting. They do not discuss this in much detail, but their grand extrapolations of this method to general applicability I don't buy.
I think the key take away from this paper is whether the halogen hydrogen bond undesignable and just a subject of serendipity?