Abstract:
:Binding hot spots are regions of proteins that, due to their potentially high contribution to the binding free energy, have high propensity to bind small molecules. We present benchmark sets for testing computational methods for the identification of binding hot spots with emphasis on fragment-based ligand discovery. Each protein structure in the set binds a fragment, which is extended into larger ligands in other structures without substantial change in its binding mode. Structures of the same proteins without any bound ligand are also collected to form an unbound benchmark. We also discuss a set developed by Astex Pharmaceuticals for the validation of hot and warm spots for fragment binding. The set is based on the assumption that a fragment that occurs in diverse ligands in the same subpocket identifies a binding hot spot. Since this set includes only ligand-bound proteins, we added a set with unbound structures. All four sets were tested using FTMap, a computational analogue of fragment screening experiments to form a baseline for testing other prediction methods, and differences among the sets are discussed.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Wakefield AE,Yueh C,Beglov D,Castilho MS,Kozakov D,Keserű GM,Whitty A,Vajda Sdoi
10.1021/acs.jcim.0c00877subject
Has Abstractpub_date
2020-12-28 00:00:00pages
6612-6623issue
12eissn
1549-9596issn
1549-960Xjournal_volume
60pub_type
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