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 Saturday, 15 January 2022 23:40:50

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 3080 Lite Hash Rate
GA102 [GeForce RTX 3080 Lite Hash Rate]
Nvidia GA102 4,749,809 257,606 18.44 1 hrs 18 mins
2 GeForce RTX 3090
GA102 [GeForce RTX 3090]
Nvidia GA102 4,544,217 253,963 17.89 1 hrs 20 mins
3 GeForce RTX 3080 Ti
GA102 [GeForce RTX 3080 Ti]
Nvidia GA102 4,295,846 249,402 17.22 1 hrs 24 mins
4 GeForce RTX 3080
GA102 [GeForce RTX 3080]
Nvidia GA102 4,225,120 249,317 16.95 1 hrs 25 mins
5 GeForce RTX 2080 Ti Rev. A
TU102 [GeForce RTX 2080 Ti Rev. A] M 13448
Nvidia TU102 3,486,401 233,740 14.92 2 hrs 37 mins
6 GeForce RTX 3070 Ti
GA104 [GeForce RTX 3070 Ti]
Nvidia GA104 3,377,890 230,813 14.63 2 hrs 38 mins
7 GeForce RTX 2080 Ti
TU102 [GeForce RTX 2080 Ti] M 13448
Nvidia TU102 3,310,144 229,039 14.45 2 hrs 40 mins
8 GeForce RTX 3070
GA104 [GeForce RTX 3070]
Nvidia GA104 2,983,452 221,187 13.49 2 hrs 47 mins
9 GeForce RTX 2080 Rev. A
TU104 [GeForce RTX 2080 Rev. A] 10068
Nvidia TU104 2,906,076 221,706 13.11 2 hrs 50 mins
10 GeForce RTX 2070 SUPER
TU104 [GeForce RTX 2070 SUPER] 8218
Nvidia TU104 2,815,690 218,346 12.90 2 hrs 52 mins
11 GeForce RTX 3060 Ti Lite Hash Rate
GA104 [GeForce RTX 3060 Ti Lite Hash Rate]
Nvidia GA104 2,683,121 214,444 12.51 2 hrs 55 mins
12 GeForce GTX 1080 Ti
GP102 [GeForce GTX 1080 Ti] 11380
Nvidia GP102 2,425,000 207,629 11.68 2 hrs 3 mins
13 GeForce RTX 2080 Super
TU104 [GeForce RTX 2080 SUPER]
Nvidia TU104 2,406,317 207,077 11.62 2 hrs 4 mins
14 GeForce RTX 2070 Rev. A
TU106 [GeForce RTX 2070 Rev. A] M 7465
Nvidia TU106 2,196,134 201,277 10.91 2 hrs 12 mins
15 GeForce RTX 3060 Ti
GA104 [GeForce RTX 3060 Ti]
Nvidia GA104 2,181,532 187,436 11.64 2 hrs 4 mins
16 GeForce RTX 2060 Super
TU106 [GeForce RTX 2060 SUPER]
Nvidia TU106 1,803,312 188,447 9.57 3 hrs 30 mins
17 GeForce RTX 2060
TU104 [GeForce RTX 2060]
Nvidia TU104 1,785,267 187,822 9.51 3 hrs 31 mins
18 GeForce RTX 3060 Lite Hash Rate
GA106 [GeForce RTX 3060 Lite Hash Rate]
Nvidia GA106 1,661,662 182,258 9.12 3 hrs 38 mins
19 Quadro RTX 6000/8000
TU102GL [Quadro RTX 6000/8000]
Nvidia TU102GL 1,384,161 173,005 8.00 3 hrs 60 mins
20 GeForce RTX 2070
TU106 [GeForce RTX 2070] M 6497
Nvidia TU106 1,343,069 141,939 9.46 3 hrs 32 mins
21 GeForce RTX 3060
GA106 [GeForce RTX 3060]
Nvidia GA106 1,283,385 162,060 7.92 3 hrs 2 mins
22 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
23 GeForce RTX 2060 Mobile
TU106M [GeForce RTX 2060 Mobile]
Nvidia TU106M 1,260,578 167,785 7.51 3 hrs 12 mins
24 GeForce GTX 1070 Ti
GP104 [GeForce GTX 1070 Ti] 8186
Nvidia GP104 1,224,231 165,776 7.38 3 hrs 15 mins
25 GeForce GTX 1660 SUPER
TU116 [GeForce GTX 1660 SUPER]
Nvidia TU116 1,219,099 165,405 7.37 3 hrs 15 mins
26 GeForce GTX 1070
GP104 [GeForce GTX 1070] 6463
Nvidia GP104 1,100,676 159,686 6.89 3 hrs 29 mins
27 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
28 Radeon VII
Vega 20 [Radeon VII] 13,284
AMD Vega 20 855,284 136,670 6.26 4 hrs 50 mins
29 GeForce GTX 1060 6GB
GP106 [GeForce GTX 1060 6GB] 4372
Nvidia GP106 810,648 144,675 5.60 4 hrs 17 mins
30 GeForce GTX 1080
GP104 [GeForce GTX 1080] 8873
Nvidia GP104 784,223 134,706 5.82 4 hrs 7 mins
31 GeForce GTX 980
GM204 [GeForce GTX 980] 4612
Nvidia GM204 676,520 135,895 4.98 5 hrs 49 mins
32 GeForce GTX 1060 3GB
GP106 [GeForce GTX 1060 3GB] 3935
Nvidia GP106 523,097 120,599 4.34 6 hrs 32 mins
33 GeForce GTX 970
GM204 [GeForce GTX 970] 3494
Nvidia GM204 492,111 121,873 4.04 6 hrs 57 mins
34 GeForce GTX 1650 Mobile / Max-Q
TU117M [GeForce GTX 1650 Mobile / Max-Q]
Nvidia TU117M 444,363 120,863 3.68 7 hrs 32 mins
35 GeForce GTX 1650
TU117 [GeForce GTX 1650]
Nvidia TU117 417,054 110,252 3.78 6 hrs 21 mins
36 P104-100
GP104 [P104-100]
Nvidia GP104 409,488 115,183 3.56 7 hrs 45 mins
37 GeForce GTX 960
GM206 [GeForce GTX 960] 2308
Nvidia GM206 388,733 113,380 3.43 7 hrs 60 mins
38 T600
TU117GL [T600]
TU117GL 341,382 107,963 3.16 8 hrs 35 mins
39 GeForce GTX 950
GM206 [GeForce GTX 950] 1572
Nvidia GM206 251,852 97,715 2.58 9 hrs 19 mins
40 GeForce GTX 770
GK104 [GeForce GTX 770] 3213
Nvidia GK104 148,255 81,963 1.81 13 hrs 16 mins
41 GeForce GTX 750 Ti
GM107 [GeForce GTX 750 Ti] 1389
Nvidia GM107 146,526 81,761 1.79 13 hrs 24 mins
42 GeForce GTX 1050 LP
GP107 [GeForce GTX 1050 LP] 1862
Nvidia GP107 141,677 50,000 2.83 8 hrs 28 mins
43 GeForce GTX 1050 Mobile
GP107M [GeForce GTX 1050 Mobile]
Nvidia GP107M 136,270 80,081 1.70 14 hrs 6 mins
44 GeForce GTX 680
GK104 [GeForce GTX 680] 3250
Nvidia GK104 126,695 77,826 1.63 15 hrs 45 mins
45 GeForce GTX 660 Ti
GK104 [GeForce GTX 660 Ti] 2634
Nvidia GK104 109,742 74,361 1.48 16 hrs 16 mins
46 Quadro K1200
GM107GL [Quadro K1200]
Nvidia GM107GL 73,755 64,922 1.14 21 hrs 8 mins

PROJECT FOLDING PPD AVERAGES BY CPU BETA

PPDDB data as of Saturday, 15 January 2022 23:40:50

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