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Multi‐target Fragments Display Versatile Binding Modes
Author(s) -
Drwal Malgorzata N.,
Bret Guillaume,
Kellenberger Esther
Publication year - 2017
Publication title -
molecular informatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.481
H-Index - 68
eISSN - 1868-1751
pISSN - 1868-1743
DOI - 10.1002/minf.201700042
Subject(s) - fragment (logic) , protein data bank (rcsb pdb) , computational biology , cheminformatics , drug discovery , promiscuity , binding site , plasma protein binding , protein structure , chemistry , computer science , biology , stereochemistry , bioinformatics , biochemistry , algorithm , ecology
Promiscuity is an interesting concept in fragment‐based drug design as fragments with low specificity can be advantageous for finding many screening hits. We present a PDB‐wide analysis of multi‐target fragments and their binding mode conservation. Focussing on multi‐target fragments, we found that the majority shows non‐conserved binding modes, even if they bind in a similar conformation or similar protein targets. Surprisingly, fragment properties alone are not able to predict whether a fragment will exhibit a versatile or conserved binding mode, emphasizing the interplay between protein and fragment features during a binding event and the importance of structure‐based modelling.