Property-Unmatched Decoys in Docking Benchmarks
| Autor: | Khanh G. Tang, Trent E. Balius, Ying Yang, Jennifer J. Young, Jiankun Lyu, John J. Irwin, Reed M. Stein, Matthew J. O’Meara, Brian K. Shoichet |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Property (programming) Computer science General Chemical Engineering Medicinal & Biomolecular Chemistry Unconstrained optimization Library and Information Sciences computer.software_genre Ligands 01 natural sciences Article Set (abstract data type) Medicinal and Biomolecular Chemistry Docking (dog) Models Theoretical and Computational Chemistry 0103 physical sciences Prospective Studies 010304 chemical physics Molecular Computation Theory and Mathematics General Chemistry 0104 chemical sciences Computer Science Applications Maxima and minima 010404 medicinal & biomolecular chemistry Benchmarking Goldilocks principle Data mining Decoy computer Protein Binding |
| Zdroj: | Journal of chemical information and modeling, vol 61, iss 2 J Chem Inf Model |
| Popis: | Enrichment of ligands versus property-matched decoys is widely used to test and optimize docking library screens. However, the unconstrained optimization of enrichment alone can mislead, leading to false confidence in prospective performance. This can arise by over-optimizing for enrichment against property-matched decoys, without considering the full spectrum of molecules to be found in a true large library screen. Adding decoys representing charge extrema helps mitigate over-optimizing for electrostatic interactions. Adding decoys that represent the overall characteristics of the library to be docked allows one to sample molecules not represented by ligands and property-matched decoys but that one will encounter in a prospective screen. An optimized version of the DUD-E set (DUDE-Z), as well as Extrema and sets representing broad features of the library (Goldilocks), is developed here. We also explore the variability that one can encounter in enrichment calculations and how that can temper one’s confidence in small enrichment differences. The new tools and new decoy sets are freely available at http://tldr.docking.org and http://dudez.docking.org. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|