title: Computational tools for in silico fragment-based drug design.
abstract: Fragment-based strategy in drug design involves the initial discovery of low-molecular mass molecules. Owing to their small-size, fragments are molecular tools to probe specific sub-pockets within a protein active site. Once their interaction within the enzyme cavity is clearly understood and experimentally validated, they represent a unique opportunity to design potent and efficient larger compounds. Computer-aided methods can essentially support the identification of suitable fragments. In this review, available tools for computational drug design are discussed in the frame of fragmentbased approaches. We analyze and review (i) available commercial fragment libraries with respect to their properties and size, (ii) computational methods for the construction of such a library, (iii) the different strategies and software packages for the selection of the fragments with predicted affinity to a given target, and (iv) tools for the in silico linkage of fragments into an actual high-affinity lead structure candidate.
authors.affiliation: Freie Universitat Berlin, Institute of Pharmacy, Department Pharmaceutical&Medicinal Chemistry, Berlin, Germany.
authors.forename: Jeremie
authors.initials: J
authors.lastname: Mortier
authors.forename: Christin
authors.initials: C
authors.lastname: Rakers
authors.forename: Raphael
authors.initials: R
authors.lastname: Frederick
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolber
mesh_terms: D020134:Catalytic Domain / Q000187:drug effects; D019295:Computational Biology; D015195:Drug Design; D011506:Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D011506:Proteins; D054852:Small Molecule Libraries