title: Predicting "Hot" and "Warm" Spots for Fragment Binding.
abstract: Computational fragment mapping methods aim to predict hotspots on protein surfaces where small fragments will bind. Such methods are popular for druggability assessment as well as structure-based design. However, to date researchers developing or using such tools have had no clear way of assessing the performance of these methods. Here, we introduce the first diverse, high quality validation set for computational fragment mapping. The set contains 52 diverse examples of fragment binding "hot" and "warm" spots from the Protein Data Bank (PDB). Additionally, we describe PLImap, a novel protocol for fragment mapping based on the Protein-Ligand Informatics force field (PLIff). We evaluate PLImap against the new fragment mapping test set, and compare its performance to that of simple shape-based algorithms and fragment docking using GOLD. PLImap is made publicly available from https://bitbucket.org/AstexUK/pli .
authors.affiliation: Astex Pharmaceuticals , 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, United Kingdom.
authors.forename: Prakash Chandra
authors.initials: PC
authors.lastname: Rathi
authors.affiliation: Astex Pharmaceuticals , 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, United Kingdom.
authors.forename: R Frederick
authors.initials: RF
authors.lastname: Ludlow
authors.affiliation: Astex Pharmaceuticals , 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, United Kingdom.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hall
authors.affiliation: Astex Pharmaceuticals , 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, United Kingdom.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Murray
authors.affiliation: Astex Pharmaceuticals , 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, United Kingdom.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Mortenson
authors.affiliation: Astex Pharmaceuticals , 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, United Kingdom.
authors.forename: Marcel L
authors.identifier: 0000-0002-6484-3328
authors.initials: ML
authors.lastname: Verdonk
mesh_terms: D030562:Databases, Protein; D006860:Hydrogen Bonding; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins