Benchmark Sets for Binding Hot Spot Identification in Fragment Based Ligand Discovery
| Autor: | Amanda E Wakefield, Marcelo Santos Castilho, Dmitri Beglov, Dima Kozakov, Adrian Whitty, Sandor Vajda, Christine Yueh, György M. Keserű |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Binding Sites
Ligand Chemistry General Chemical Engineering Proteins Hot spot (veterinary medicine) General Chemistry Plasma protein binding Computational biology Library and Information Sciences Ligands Small molecule Article Computer Science Applications Set (abstract data type) Benchmarking Protein structure Fragment (logic) Binding site Protein Binding |
| Zdroj: | J Chem Inf Model |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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