PROJECT #18700 RESEARCH FOR CANCER
FOLDING PERFORMANCE PROFILE

PROJECT SUMMARY

Von Hippel-Lindau (VHL) syndrome is a rare disease that causes tumors and cysts to develop and grow in the body.

These tumors usually are non-cancerous, but some, especially tumors that develop in the kidney and pancreas, may become cancerous.

VHL syndrome is caused by a mutation in the VHL gene, which decreases the VHL protein’s ability to act as an E3 ligase and ubiquitinate the α subunit of hypoxia-inducible factor (HIF), which decreases proteolysis of HIF proteins.

The elevated HIF levels are responsible for the hypervascularization in renal cell carcinoma associated with the VHL syndrome disease state.

This project investigates the design of heterobifunctional molecules, also known as PROteolysis TArgeting Chimeras (PROTACs), which can bind both the VHL and HIF2α and help regulate the degradation of HIF2α.

Experimental measurements can provide insights to the challenge of PROTAC optimization, but the design space is too large to test every potential molecule design.

Therefore, molecular dynamic simulations will be run on potential ligand candidates to reduce the amount of possible PROTAC hits and reduce the experiments necessary for validation.

Initially the warhead domain, the PROTAC’s binding domain to HIF2α, will be developed by running simulations using various different structures already bound to the protein and determining the stability of the bound state for each potential structure.

Then the linker region, the structure that connects the two binding domains, of the PROTAC will be developed by running simulations to determine the ternary structure for the VHL-PROTAC- HIF2α complex.

All the computed values of kon, koff, ΔH, ΔS, and ΔG use AMBER force fields for Protein-Protein and Protein-Ligand's interactions.

Roivant is using published PROTAC-bound ternary complexes, plus some data generated internally for the F@h projects, and all simulation data is being made publicly available..

PROJECT INFO

Manager(s): Rafal Wiewiora

Institution: Roivant Sciences (Silicon Therapeutics)

Project URL: roivant.com

PROJECT WORK UNIT SUMMARY

Atoms: 40,000

Core: OPENMM_22

Status: Public

PROJECT FOLDING PPD AVERAGES BY GPU

PPDDB data as of Thursday, 01 December 2022 06:13:23

Rank
Project
Model Name
Folding@Home Identifier
Make
Brand
GPU
Model
PPD
Average
Points WU
Average
WUs Day
Average
WU Time
Average
1 GeForce RTX 3090
GA102 [GeForce RTX 3090]
Nvidia GA102 4,622,348 253,141 18.26 1 hrs 19 mins
2 GeForce RTX 3080 Ti
GA102 [GeForce RTX 3080 Ti]
Nvidia GA102 4,369,637 249,299 17.53 1 hrs 22 mins
3 GeForce RTX 3080
GA102 [GeForce RTX 3080]
Nvidia GA102 4,146,472 246,151 16.85 1 hrs 25 mins
4 GeForce RTX 3080 Lite Hash Rate
GA102 [GeForce RTX 3080 Lite Hash Rate]
Nvidia GA102 3,941,505 239,582 16.45 1 hrs 28 mins
5 GeForce RTX 2080 Ti Rev. A
TU102 [GeForce RTX 2080 Ti Rev. A] M 13448
Nvidia TU102 3,676,476 238,127 15.44 2 hrs 33 mins
6 GeForce RTX 2080 Rev. A
TU104 [GeForce RTX 2080 Rev. A] 10068
Nvidia TU104 3,242,785 228,923 14.17 2 hrs 42 mins
7 GeForce RTX 2080 Ti
TU102 [GeForce RTX 2080 Ti] M 13448
Nvidia TU102 3,235,180 223,961 14.45 2 hrs 40 mins
8 GeForce RTX 3070 Ti
GA104 [GeForce RTX 3070 Ti]
Nvidia GA104 3,194,717 227,178 14.06 2 hrs 42 mins
9 GeForce RTX 3070
GA104 [GeForce RTX 3070]
Nvidia GA104 2,920,007 218,949 13.34 2 hrs 48 mins
10 GeForce RTX 3070 Mobile / Max-Q
GA104M [GeForce RTX 3070 Mobile / Max-Q]
Nvidia GA104M 2,726,463 217,738 12.52 2 hrs 55 mins
11 RTX A4000
GA104GL [RTX A4000]
Nvidia GA104GL 2,525,990 211,221 11.96 2 hrs 0 mins
12 GeForce RTX 2070 SUPER
TU104 [GeForce RTX 2070 SUPER] 8218
Nvidia TU104 2,414,516 203,585 11.86 2 hrs 1 mins
13 GeForce RTX 2080 Super
TU104 [GeForce RTX 2080 SUPER]
Nvidia TU104 2,345,256 205,569 11.41 2 hrs 6 mins
14 GeForce RTX 3060 Ti Lite Hash Rate
GA104 [GeForce RTX 3060 Ti Lite Hash Rate]
Nvidia GA104 2,337,726 196,363 11.91 2 hrs 1 mins
15 GeForce RTX 2080
TU104 [GeForce RTX 2080]
Nvidia TU104 2,322,981 204,846 11.34 2 hrs 7 mins
16 GeForce GTX 1080 Ti
GP102 [GeForce GTX 1080 Ti] 11380
Nvidia GP102 2,294,879 203,371 11.28 2 hrs 8 mins
17 GeForce RTX 2070 Rev. A
TU106 [GeForce RTX 2070 Rev. A] M 7465
Nvidia TU106 2,212,022 201,549 10.98 2 hrs 11 mins
18 GeForce RTX 3060 Ti
GA104 [GeForce RTX 3060 Ti]
Nvidia GA104 2,185,273 191,904 11.39 2 hrs 6 mins
19 GeForce RTX 2070 SUPER Mobile / Max-Q
TU104M [GeForce RTX 2070 SUPER Mobile / Max-Q]
Nvidia TU104M 2,182,284 199,776 10.92 2 hrs 12 mins
20 GeForce RTX 3060
GA104 [GeForce RTX 3060]
Nvidia GA104 1,825,016 188,411 9.69 2 hrs 29 mins
21 GeForce RTX 2060 Super
TU106 [GeForce RTX 2060 SUPER]
Nvidia TU106 1,821,339 188,962 9.64 2 hrs 29 mins
22 GeForce RTX 2060
TU104 [GeForce RTX 2060]
Nvidia TU104 1,761,271 186,781 9.43 3 hrs 33 mins
23 GeForce RTX 2060
TU106 [Geforce RTX 2060]
Nvidia TU106 1,689,639 183,939 9.19 3 hrs 37 mins
24 GeForce RTX 3060 Lite Hash Rate
GA106 [GeForce RTX 3060 Lite Hash Rate]
Nvidia GA106 1,590,856 178,329 8.92 3 hrs 41 mins
25 GeForce RTX 3070 Mobile / Max-Q 8GB/16GB
GA104M [GeForce RTX 3070 Mobile / Max-Q 8GB/16GB]
Nvidia GA104M 1,534,910 177,518 8.65 3 hrs 47 mins
26 Quadro RTX 6000/8000
TU102GL [Quadro RTX 6000/8000]
Nvidia TU102GL 1,375,026 172,391 7.98 3 hrs 1 mins
27 GeForce RTX 3060
GA106 [GeForce RTX 3060]
Nvidia GA106 1,354,002 164,442 8.23 3 hrs 55 mins
28 GeForce GTX 1070 Ti
GP104 [GeForce GTX 1070 Ti] 8186
Nvidia GP104 1,333,121 170,289 7.83 3 hrs 4 mins
29 GeForce RTX 2060 Mobile
TU106M [GeForce RTX 2060 Mobile]
Nvidia TU106M 1,322,976 170,197 7.77 3 hrs 5 mins
30 GeForce RTX 3060 Mobile / Max-Q
GA106M [GeForce RTX 3060 Mobile / Max-Q]
Nvidia GA106M 1,267,102 167,337 7.57 3 hrs 10 mins
31 GeForce RTX 2070
TU106 [GeForce RTX 2070] M 6497
Nvidia TU106 1,202,167 159,817 7.52 3 hrs 11 mins
32 GeForce GTX 1660 SUPER
TU116 [GeForce GTX 1660 SUPER]
Nvidia TU116 1,134,809 160,196 7.08 3 hrs 23 mins
33 GeForce GTX 1070
GP104 [GeForce GTX 1070] 6463
Nvidia GP104 1,124,386 160,775 6.99 3 hrs 26 mins
34 Geforce RTX 3050
GA106 [Geforce RTX 3050]
Nvidia GA106 1,120,804 160,416 6.99 3 hrs 26 mins
35 GeForce GTX 980 Ti
GM200 [GeForce GTX 980 Ti] 5632
Nvidia GM200 1,086,021 158,381 6.86 4 hrs 30 mins
36 Radeon RX 6800/6800 XT / 6900 XT
Navi 21 [Radeon RX 6800/6800 XT / 6900 XT]
AMD Navi 21 971,425 152,255 6.38 4 hrs 46 mins
37 GeForce GTX 1080
GP104 [GeForce GTX 1080] 8873
Nvidia GP104 927,996 144,616 6.42 4 hrs 44 mins
38 Quadro P4000
GP104GL [Quadro P4000]
Nvidia GP104GL 875,541 148,688 5.89 4 hrs 5 mins
39 Radeon VII
Vega 20 [Radeon VII] 13,284
AMD Vega 20 855,284 136,670 6.26 4 hrs 50 mins
40 GeForce GTX 1660 Mobile
TU116M [GeForce GTX 1660 Mobile]
Nvidia TU116M 831,572 144,370 5.76 4 hrs 10 mins
41 GeForce GTX 1060 6GB
GP106 [GeForce GTX 1060 6GB] 4372
Nvidia GP106 779,985 142,429 5.48 4 hrs 23 mins
42 GeForce GTX 980
GM204 [GeForce GTX 980] 4612
Nvidia GM204 648,273 132,744 4.88 5 hrs 55 mins
43 GeForce GTX 970
GM204 [GeForce GTX 970] 3494
Nvidia GM204 525,465 124,524 4.22 6 hrs 41 mins
44 GeForce GTX 1060 3GB
GP106 [GeForce GTX 1060 3GB] 3935
Nvidia GP106 522,667 121,178 4.31 6 hrs 34 mins
45 GeForce GTX 1650 Mobile / Max-Q
TU117M [GeForce GTX 1650 Mobile / Max-Q]
Nvidia TU117M 517,167 124,649 4.15 6 hrs 47 mins
46 GeForce GTX 1650
TU117 [GeForce GTX 1650]
Nvidia TU117 423,600 111,439 3.80 6 hrs 19 mins
47 P104-100
GP104 [P104-100]
Nvidia GP104 409,488 115,183 3.56 7 hrs 45 mins
48 GeForce GTX 980M
GM204 [GeForce GTX 980M] 3189
Nvidia GM204 406,171 115,092 3.53 7 hrs 48 mins
49 GeForce GTX 960
GM206 [GeForce GTX 960] 2308
Nvidia GM206 388,733 113,380 3.43 7 hrs 60 mins
50 T600
TU117GL [T600]
Intel TU117GL 323,592 106,008 3.05 8 hrs 52 mins
51 GeForce GTX 950
GM206 [GeForce GTX 950] 1572
Nvidia GM206 235,390 94,268 2.50 10 hrs 37 mins
52 P106-100
GP106 [P106-100]
Nvidia GP106 201,255 87,293 2.31 10 hrs 25 mins
53 GeForce GTX 1050 Ti Mobile
GP107M [GeForce GTX 1050 Ti Mobile]
Nvidia GP107M 173,204 82,127 2.11 11 hrs 23 mins
54 GeForce GTX 770
GK104 [GeForce GTX 770] 3213
Nvidia GK104 152,236 82,563 1.84 13 hrs 1 mins
55 GeForce GTX 750 Ti
GM107 [GeForce GTX 750 Ti] 1389
Nvidia GM107 145,744 81,602 1.79 13 hrs 26 mins
56 GeForce GTX 1050 LP
GP107 [GeForce GTX 1050 LP] 1862
Nvidia GP107 141,677 50,000 2.83 8 hrs 28 mins
57 GeForce GTX 1050 Mobile
GP107M [GeForce GTX 1050 Mobile]
Nvidia GP107M 136,270 80,081 1.70 14 hrs 6 mins
58 GeForce GTX 680
GK104 [GeForce GTX 680] 3250
Nvidia GK104 136,032 79,477 1.71 14 hrs 1 mins
59 Quadro P620
GP107GL [Quadro P620]
Nvidia GP107GL 127,885 77,686 1.65 15 hrs 35 mins
60 GeForce GTX 660 Ti
GK104 [GeForce GTX 660 Ti] 2634
Nvidia GK104 106,317 73,159 1.45 17 hrs 31 mins
61 GeForce GT 1030
GP108 [GeForce GT 1030] 1127
Nvidia GP108 92,796 70,349 1.32 18 hrs 12 mins
62 Quadro K1200
GM107GL [Quadro K1200]
Nvidia GM107GL 73,755 64,922 1.14 21 hrs 8 mins
63 GeForce GTX 660
GK106 [GeForce GTX 660]
Nvidia GK106 73,008 64,735 1.13 21 hrs 17 mins
64 GTX 650 Ti Boost
GK106 [GTX 650 Ti Boost]
Nvidia GK106 49,431 50,000 0.99 24 hrs 17 mins
65 GeForce GT 730
GK208B [GeForce GT 730] 692.7
Nvidia GK208B 31,745 50,000 0.63 38 hrs 48 mins

PROJECT FOLDING PPD AVERAGES BY CPU BETA

PPDDB data as of Thursday, 01 December 2022 06:13:23

Rank
Project
CPU Model Logical
Processors (LP)
PPD-PLP
AVG PPD per 1 LP
ALL LP-PPD
(Estimated)
Make