Fig. 10. Fragments bridging multiple adenosine sites provide direct merging opportunities.

(A) Sliced view of the adenosine site (white surface and gray interior) and a symmetry mate (blue surface and interior) showing the deep pocket created by crystal packing in the P4₃ crystals. The 66 fragments that hydrogen bond with the Lys¹¹ backbone nitrogen are shown as sticks. (B) Plot showing distances between the symmetry mate (Lys¹¹-N) and the adenine subsite (Asp²²-Oδ, Ile²³-N, and Ala¹⁵⁴-O) for all fragments identified in the adenosine site. Dotted lines show the 3.5-Å cutoff used to classify hydrogen bonds. (C) An example showing 1 of the 24 fragments that bound in the adenosine site, yet only formed a hydrogen bond with the symmetry mate. (D) An example of one of the fragments that bridged the 9- to 11-Å gap between the adenine subsite and the symmetry mate. (E and F) Opportunities for fragment linking and merging. Adjacent or overlapping fragments were initially merged into a single new compound. Examples of readily available make-on-demand compounds are shown.