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BACE - Overview

Challenge timeframe: Sep 04, 2018 to Dec 04, 2018


Updates

2018-12-13 - Participant files are now available on the "Data Download" page. You must be logged in first to access the files.

2018-12-07 - Answers to the challenges are now available: BACE_score_compounds_D3R_GC4_answers.csv and BACE_FEset_compounds_D3R_GC4_answers.csv

2018-10-11 - An update was made to the Challenge submission instructions for Stage 1B. Also, for Stage 1B, when appropriate, please select your protocol from Stage 1A rather than reuploading a new protocol file.

Challenge submission instructions are available. Example and template files are also available.
Stage 1 - Dataset packet provided: BACE_initial_packet_to_participants.zip
  • BACE_target_D3R_GC4.fasta: Protein sequence file of the BACE construct used.
  • BACE_pose_compounds_D3R_GC4.csv: CSV file of 20 compounds and their corresponding SMILES.
  • BACE_score_compounds_D3R_GC4.csv: CSV file of 154 compounds and their corresponding SMILES string.
  • BACE_FESet_compounds_D3R_GC4.csv: CSV file of 34 compounds for explicit-solvent relative or absolute free energy calculations.
  • 5ygx, chain A: Reference protein structure to use for superimposition. Download: https://drugdesigndata.org/upload/community-components/5YGX_chainA.pdb. Note: The original PDB file has been altered to remove the 3 negative residues at the beginning and the residue numbered 0.

Introduction to BACE

Beta-Secretase 1 (BACE) is a transmembrane aspartic-acid protease human protein encoded by the BACE1 gene. BACE is essential for the generation of beta-amyloid peptide in neural tissue1, a component of amyloid plaques widely believed to be critical in the development of Alzheimer's, rendering BACE an attractive therapeutic target for this devastating disease2.

The BACE dataset provided herein comprises small molecule inhibitors across a three order of magnitude (nM to μM) range of IC50s along with previously undisclosed crystallographic structures. Specifically, we provide 154 BACE inhibitors for affinity, 20 for pose, and 34 for free energy prediction. This dataset was kindly provided by Novartis.

BACE Assay Conditions

A description of the assay conditions employed for GC4 BACE affinity data generation can be found in the following reference3.

BACE Crystallization Conditions

A detailed description of the crystallization conditions employed for GC4 BACE crystal structure generation can be found in the supplementary material of the following reference4.

BACE.png
Representative crystal structures of BACE (PDB 5YGX).

References

  1. Vassar, R.; Kovacs, D. M.; Yan, R.; Wong, P. C. J. Neurosci. 2009, 29 (41), 12787-12794.
  2. Prati, F.; Bottegoni, G.; Bolognesi, M. L.; Cavalli, A. J. Med. Chem. 2018, 61 (3), 619-637.
  3. Hanessian, S.; Yang, G.; Rondeau, J.-M.; Neumann, U.; Betschart, C.; Tintelnot-Blomley, M. J. Med. Chem. 2006, 49 (15), 4544-4567.
  4. Machauer, R.; Laumen, K.; Veenstra, S.; Rondeau, J.-M.; Tintelnot-Blomley, M.; Betschart, C.; Jaton, A.-L.; Desrayaud, S.; Staufenbiel, M.; Rabe, S.; Paganetti, P.; Neumann, U. Bioorg. Med. Chem. Lett. 2009, 19 (5), 1366-1370.

BACE - Data Download

Challenge timeframe: Sep 04, 2018 to Dec 04, 2018


Stage 1a (09/04/2018 to 10/04/2018)
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Stage 1b (10/08/2018 to 10/19/2018)
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Stage 2 (10/22/2018 to 12/04/2018)
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BACE - Protocols

Challenge timeframe: Sep 04, 2018 to Dec 04, 2018


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BACE - Submissions

Challenge timeframe: Sep 04, 2018 to Dec 04, 2018


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BACE - Evaluation Results

Challenge timeframe: Sep 04, 2018 to Dec 04, 2018


Evaluation Results

Evaluation results are not available yet.
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