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2381: CCHFV Protease Round 9

Closed since over 2 years ago

Intermediate Overall Small Molecule Design

Summary

Created
November 17, 2023
Expires
Max points
100
Description

The Crimean-Congo Hemorrhagic Fever (CCHF) is a life-threatening zoonotic disease caused by a tick-borne virus. Recent research has revealed the significant role of the viral-encoded Ovarian Tumor (OTU) deubiquitinase in the CCHFV replication process. Based on the most promising compounds, this puzzle will focus on getting an inhibitor for this protein. As the CCHFV-OTU protease interacts with another protein (ubiquitin), the interaction surface is quite large and superficial, making it a challenging binding pocket. For this round we will be focusing on the lower binding pocket. We have also adjusted the objectives to accommodate larger small molecules, as one of our goals is to inhibit protein-protein interactions. In many cases, such inhibitors possess a higher molecular weight. For more details check out the Crimean-Congo Hemorrhagic Fever blog post.

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Comments

Sciren Staff Lv 1

Objectives

Maximum bonus: +7750

Compound Library (max +750)
Gives a bonus if your current compound is in the library. This uses a local cached version of the Compound Library search results to determine if the compound is in the library. If you manually create a compound that happens to be in the library (or if you load a shared solution with an on-library compound), you may need to submit the compound to the compound library search and wait to get the results back before the objective can properly recognize that the compound is in the library. (If the objective is not updating, try wiggling the structure. See this forum post for more discussion.)

Torsion Quality (max +1000)
Keeps bond rotations in a good range. Using Wiggle or Tweak Ligand can fix bad torsions. (Show highlights torsions to be rotated.)

Number of Rotatable Bonds (max +1000)
Intended to keep the ligand from getting too big and floppy. You can reduce rotatable bonds by deleting groups or forming rings. (Show highlights rotatable bonds.)

Ligand TPSA (max +1000)
Topological Polar Surface Area - Keeps the polar surface area (including buried polar surface) low. To improve, try removing oxygens and nitrogens. (Show highlights atoms contributing to higher TPSA.)

Ligand cLogP (max +1000)
A measure of polarity - Keeps the molecule from getting too hydrophobic. To improve, try adding polar oxygens and nitrogens. (Show highlights atoms contributing to higher cLogP.)

Bad Groups (max +1000)
Gives a bonus for avoiding groups that interfere with assays, which are far from the compounds in the library, or which otherwise have issues. (Show highlights groups at issue.)

Molecular Weight (max +1000)
Keeps the ligand within a reasonable size limit.

Synthetic Accessibility (max +1000)
Keeps the ligand from going too far from the compounds in the library. (Show highlights parts of the molecule at issue.)