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| - Automatic and Efficient Decomposition of Two-Dimensional Structures of Small Molecules forFragment-Based High-Throughput Docking
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| - The computer program DAIM (Decomposition and Identification of Molecules) has been developed toautomatically break up compounds in small-molecule libraries for fragment-based docking as well as databaseanalysis. Here, DAIM is evaluated on 130 ligands derived from known crystal structures of ligand−proteincomplexes. The decomposition and a new fingerprint-based identification technique are used to select anchorfragments for docking. The docking results show that the DAIM selection is superior to size-based or randomselection of fragments. To evaluate the usefulness for analyzing the fragment composition of a large library,DAIM is applied to a collection of about 1.85 million commercially available compounds. Interestingly, itis found that the set of most frequent cyclic and acyclic fragments originating from the decomposition ofthe 1.85 million molecules shows a large overlap with the most frequent fragments in a library of 5120known drugs. DAIM has been successfully used in the in silico screening for inhibitors of β-secretase andEphB4 kinase by fragment-based high-throughput docking. Possible future applications for de novo liganddesign are briefly discussed.
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