We present an analysis of chemical fragments from lead-like ligands in the Protein Data Bank (PDB) that form hydrogen bonds to either main or side chains of amino acids in protein binding sites. A fragment is defined as the largest ring assembly containing the atoms involved in hydrogen bond(s) to the protein. Some case studies will be present. For example, a total of 462 unique fragments were found in 2,038 unique ligands from over 8,000 protein ligand structures in the PDB that form hydrogen bonds to the side chains of Asp, Glu, Arg, and His. Some fragments are observed to interact with Asp but not with Glu, and vice versa, despite these side chains share the same chemical moiety. Our finding of chemical fragment provides information that is useful for drug design, especially in the area of fragment-based design, chemical library design, and selection of screening compounds.

Knowledge-based chemical fragment analysis in protein binding sites

245th National Meeting (2013)

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