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2360: CACHE SARS Nsp3 Reranking challenge: Round 1

Closed since over 2 years ago

Intermediate Overall Small Molecule Design

Summary

Created
September 21, 2023
Expires
Max points
100
Description

This puzzle is a followup to the SARS-CoV-2 Nsp3 macrodomain design challenges. Help us rank potential active compounds!

Phase 2 of the CACHE challenge #3 is a ranking of all 1739 molecules which the various participants submitted for testing. In this puzzle you don't have free design with the Small Molecule Design tool, but you instead have the Ligand Queue which will provide you with a small number of possible compounds. You can then use the compound library panel to find related compounds specifically from the library of tested compounds. Then attempt to find the best binding position for the compounds.

Note: To get the most out of the small molecule design tools, we recommend changing you view settings to the Small Molecule Design Preset.

Ranking designed compounds and figuring out which bind are an important part of designing new molecules, and with this puzzle, we're testing out how well the Ligand Queue and Compound Library tools work for evaluating medium-sized libraries. Bounce back and forth between the ligand queue and the compound library search to seek out compounds you think bind best. (Note that all compounds should be accessible within two compound library jumps from a ligand queue molecule.)

Participation in CACHE puzzles is subject to the CACHE Terms of Participation, in particular “the Challenge IP [including Challenge Compounds] will be made freely available in the public domain pursuant to Creative Commons Attribution Only (CC-BY 4.0 or subsequent versions) licensing terms, with the intent that such Challenge IP may be Used and practiced by Users for any purpose”.

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Comments

LociOiling Lv 1

Late to the game, but keeping up with puzzle 2363 and 2666, here are properties for the ligand queue entries.

weight cLogP PSA heavy atoms H-bond donors H-bond acceptors rotatable bonds
258.296 1.90288 47.26 19 1 3 1
262.357 2.59240 51.45 19 1 5 7
271.263 2.19384 59.16 19 1 4 4
274.328 0.62800 78.96 20 2 7 4
292.295 0.74164 121.37 21 3 8 6
308.341 2.83992 93.03 23 4 6 1
314.338 1.58250 81.43 21 1 6 4
315.356 1.79350 86.38 23 2 7 7
317.389 1.27460 78.07 23 2 6 7
317.393 1.82572 76.16 23 1 7 1
318.381 0.78242 89.08 23 1 8 5
323.260 0.18900 111.47 21 1 9 8
327.402 1.24100 72.91 22 0 6 7
335.404 3.01042 99.69 24 4 7 10
342.421 -0.53970 104.53 23 2 8 5
347.375 0.28392 113.23 25 2 9 7
351.762 2.70400 84.08 22 2 6 6
366.450 3.45630 94.77 26 3 7 5
368.210 1.97670 77.04 22 2 6 7
368.481 2.58100 81.51 27 3 6 4
368.484 1.82300 100.10 24 2 7 6
369.479 2.88230 94.88 25 2 7 3
378.450 1.77380 103.78 26 2 7 10
382.825 2.90010 91.40 25 0 7 5
390.417 1.32140 118.32 27 2 8 8
391.262 3.38612 67.98 26 1 7 4
400.258 1.27550 99.26 23 1 8 3
411.414 2.10970 147.99 30 6 9 8
419.428 2.41714 87.47 30 2 7 10
426.401 3.32620 40.62 29 0 4 8

Notes:

  1. The compound with weight 308.341 is different than the compound with the same weight that appears in puzzle 2366.
  2. The compound with weight 327.402 is different than the compound with the same weight that appears in puzzle 2366.
  3. The compound with weight 411.414 is provided as a convenient "known" starting point.

LociOiling Lv 1

Here are the SMILES and chemical formulas.

weight cLogP PSA SMILES formula
258.296 1.90288 47.26 N#Cc1ccc(N2CC3CC4CC3C2C4O)c(F)c1 C15H15FN2O
262.357 2.59240 51.45 CCC(CC)C(CNc1cccc2nncn12)OC C14H22N4O
271.263 2.19384 59.16 Cc1cc(C(=O)OCC2CC(F)(F)C2)c(=O)[nH]c1C C13H15F2NO3
274.328 0.62800 78.96 c1nc(NC[C@H]2CN(C3CC3)CCO2)c2nc[nH]c2n1 C13H18N6O
292.295 0.74164 121.37 Cc1noc(C)c1CCC(=O)NCc1cnc(O)nc1O C13H16N4O4
308.341 2.83992 93.03 Cc1cc2nc(N)[nH]c2cc1-1ccc2c(c1)NC(=O)C(C)O2 C16H26N4O2
314.338 1.58250 81.43 COC1(CNc2nc3cccc(F)c3o2)CCs(=O)(=O)C1 C13H15FN2O4S
315.356 1.79350 86.38 CN(CCCc1cc(-c2ccc(F)cc2)n[nH]1)Cc1nn[nH]n1 C15H18FN7
317.389 1.27460 78.07 CN(CC(C)(CO)CO)C(=O)c1nc(C2CC2)n2ccccc12 C17H23N3O3
317.393 1.82572 76.16 Cc1nc(N2CC(C)(C)OC3(CCOCC3)C2)c2cn[nH]c2n1 C16H23N5O2
318.381 0.78242 89.08 Cc1noc(CN2CCCCC(NCc3nccn3C)C2=O)n1 C15H22N6O2
323.260 0.18900 111.47 O=C(CSc1nnnn1CC(F)(F)F)OCc1nc[nH]n1 C8H8F3N7O2S
327.402 1.24100 72.91 CCN(CC)C(=O)CS(=O)(=O)Cc1cccc2c1OCCO2 C15H21NO5S
335.404 3.01042 99.69 C=CC(CO)NC(=O)Nc1cc(C)cc(NC(=O)OC(C)(C)C)c1 C17H25N3O4
342.421 -0.53970 104.53 Cn1cc(S(=O)(=O)N2CC(NC(=O)C3CCCC(O)C3)C2)cn1 C14H22N4O4S
347.375 0.28392 113.23 Cc1ccoc1c(=O)NC[C@]1(C)CCCN1C(=O)Cn1cn[nH]c1=O C16H21N5O4
351.762 2.70400 84.08 CC(NS(=O)c1cccc(Cl)c1OC(F)F)c1c[nH]cn1 C12H12ClF2N3O2S
366.450 3.45630 94.77 Cc1c(C#N)sc2ccc(NC(=O)Nc3ccn(C4CCNC4)n3)cc12 C18H18N6OS
368.210 1.97670 77.04 C=CCN(Cc1cc(Br)ccc1F)C(=O)Cn1ncnc1N C14H15BrFN5O
368.481 2.58100 81.51 O[C@H]1CC2(CCCC2)CN(c2nccc(NCc3ccccc3)n2)C[C@H]1O C21H28N4O2
368.484 1.82300 100.10 NS(=O)(=O)c1ccc(OCCSc2nn3n2CCCCCC3)cc1 C15H20N4O3S2
369.479 2.88230 94.88 Nc1nc(CSc2nc3ncccn3n2)nc2sc3c(c12)CCCC3 C16H15N7S2
378.450 1.77380 103.78 CCCC(NC(=O)C(CCSC)N1C(=O)c2ccccc2c1=O)C(=O)O C18H28N2O5S
382.825 2.90010 91.40 CCCc1cc(=O)oc2cc(OS(=O)(=O)c3ncn(C)c3Cl)ccc12 C16H15ClN2O5S
390.417 1.32140 118.32 O=C(C=Cc1ccc[nH]1)O[C@H]1CS(=O)(=O)C[C@@H]1OC(=O)C=Cc1ccc[nH]1 C18H18N2O6S
391.262 3.38612 67.98 Cc1cc(NC(=O)c2cnn3c2N(C)CC3)nn1-c1ccc(Cl)c(Cl)c1 C17H16Cl2N6O
400.258 1.27550 99.26 O=C(c1n[nH]c2ncc(Br)cc12)N1CCCn(C2CC2)S1(=O)=O C13H14BrN5O3S
411.414 2.10970 147.99 O=C([O-])C2Cc1c(O)cccc1[C@@H]2NC(=O)c4ccc(NC(=O)NC3CC3)cc4O C21H20N3O6
419.428 2.41714 87.47 COc1c(F)ccc(C(=O)N(C)CC(=O)NCC(=O)Nc2c(C)cccc2c)c1F C21H23F2N3O4
426.401 3.32620 40.62 CC(C)(CCC(=O)N1C[C@H]2[C@@H](C1)[C@@H]2C(F)(F)F)C=ON1C[C@H]2[C@@H](C1)[C@@H]2C(F)(F)F C19H26F6N2O2

Notes:

  1. The compound with weight 308.341 is different than the compound with the same weight that appears in puzzle 2366.
  2. The compound with weight 327.402 is different than the compound with the same weight that appears in puzzle 2366.
  3. The compound with weight 411.414 is provided as a convenient "known" starting point.