D3R grand challenge 4: blind prediction of protein–ligand poses, affinity rankings, and relative binding free energies

The Drug Design Data Resource (D3R) aims to identify best practice methods for computer aided drug design through blinded ligand pose prediction and affinity challenges. Herein, we report on the results of Grand Challenge 4 (GC4). GC4 focused on proteins beta secretase 1 and Cathepsin S, and was run...

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Bibliographic Details
Published in:Journal of computer-aided molecular design 2020-02, Vol.34 (2), p.99-119
Main Authors: Parks, Conor D., Gaieb, Zied, Chiu, Michael, Yang, Huanwang, Shao, Chenghua, Walters, W. Patrick, Jansen, Johanna M., McGaughey, Georgia, Lewis, Richard A., Bembenek, Scott D., Ameriks, Michael K., Mirzadegan, Tara, Burley, Stephen K., Amaro, Rommie E., Gilson, Michael K.
Format: Article
Language:English
Subjects:
Affinity
Amyloid Precursor Protein Secretases - antagonists & inhibitors
Amyloid Precursor Protein Secretases - metabolism
Animal Anatomy
Aspartic Acid Endopeptidases - antagonists & inhibitors
Aspartic Acid Endopeptidases - metabolism
BASIC BIOLOGICAL SCIENCES
Best practice
Biochemistry & molecular biology
Biophysics
Blinded prediction challenge
CAD
Chemistry
Chemistry and Materials Science
Computer aided design
Computer Applications in Chemistry
Computer science
Crystal structure
D3R
Docking
Drug Design
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Free-energy
Histology
Humans
Identification methods
Ligand ranking
Ligands
Machine Learning
Molecular Docking Simulation
Morphology
Physical Chemistry
Proteins
Scoring
Small Molecule Libraries - chemistry
Small Molecule Libraries - pharmacology
Thermodynamics
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Summary:The Drug Design Data Resource (D3R) aims to identify best practice methods for computer aided drug design through blinded ligand pose prediction and affinity challenges. Herein, we report on the results of Grand Challenge 4 (GC4). GC4 focused on proteins beta secretase 1 and Cathepsin S, and was run in an analogous manner to prior challenges. In Stage 1, participant ability to predict the pose and affinity of BACE1 ligands were assessed. Following the completion of Stage 1, all BACE1 co-crystal structures were released, and Stage 2 tested affinity rankings with co-crystal structures. We provide an analysis of the results and discuss insights into determined best practice methods.
ISSN:0920-654X
1573-4951
DOI:10.1007/s10822-020-00289-y