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Benchmark Sets for Binding Hot Spot Identification in Fragment-Based Ligand Discovery.

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 Model

journal_title

Journal of chemical information and modeling

authors

Wakefield AE,Yueh C,Beglov D,Castilho MS,Kozakov D,Keserű GM,Whitty A,Vajda S

doi

10.1021/acs.jcim.0c00877

subject

Has Abstract

pub_date

2020-12-28 00:00:00

pages

6612-6623

issue

12

eissn

1549-9596

issn

1549-960X

journal_volume

60

pub_type

杂志文章

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