PROJECT #18706 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: 188,026
Core: 0x22
Status: Public
PROJECT FOLDING PPD AVERAGES BY GPU
PPDDB data as of Tuesday, 07 February 2023 06:14:50
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 4090 AD102 [GeForce RTX 4090] |
Nvidia | AD102 | 15,205,529 | 950,250 | 16.00 | 1 hrs 30 mins |
2 | GeForce RTX 3090 Ti GA102 [GeForce RTX 3090 Ti] |
Nvidia | GA102 | 8,498,538 | 796,706 | 10.67 | 2 hrs 15 mins |
3 | GeForce RTX 3090 GA102 [GeForce RTX 3090] |
Nvidia | GA102 | 7,425,095 | 752,120 | 9.87 | 2 hrs 26 mins |
4 | GeForce RTX 3080 Ti GA102 [GeForce RTX 3080 Ti] |
Nvidia | GA102 | 7,232,263 | 753,849 | 9.59 | 3 hrs 30 mins |
5 | GeForce RTX 3080 12GB GA102 [GeForce RTX 3080 12GB] |
Nvidia | GA102 | 7,213,754 | 733,043 | 9.84 | 2 hrs 26 mins |
6 | GeForce RTX 3080 Lite Hash Rate GA102 [GeForce RTX 3080 Lite Hash Rate] |
Nvidia | GA102 | 6,431,210 | 718,204 | 8.95 | 3 hrs 41 mins |
7 | Radeon RX 6950 XT Navi 21 [Radeon RX 6950 XT] |
AMD | Navi 21 | 5,879,197 | 708,193 | 8.30 | 3 hrs 53 mins |
8 | GeForce RTX 3080 GA102 [GeForce RTX 3080] |
Nvidia | GA102 | 5,741,438 | 691,499 | 8.30 | 3 hrs 53 mins |
9 | GeForce RTX 2080 Ti Rev. A TU102 [GeForce RTX 2080 Ti Rev. A] M 13448 |
Nvidia | TU102 | 5,215,873 | 676,082 | 7.71 | 3 hrs 7 mins |
10 | GeForce RTX 2080 Ti TU102 [GeForce RTX 2080 Ti] M 13448 |
Nvidia | TU102 | 5,071,772 | 663,842 | 7.64 | 3 hrs 8 mins |
11 | Radeon RX 6800/6800 XT / 6900 XT Navi 21 [Radeon RX 6800/6800 XT / 6900 XT] |
AMD | Navi 21 | 4,662,940 | 638,634 | 7.30 | 3 hrs 17 mins |
12 | GeForce RTX 3070 Ti GA104 [GeForce RTX 3070 Ti] |
Nvidia | GA104 | 4,554,693 | 647,580 | 7.03 | 3 hrs 25 mins |
13 | GeForce RTX 3070 GA104 [GeForce RTX 3070] |
Nvidia | GA104 | 4,111,080 | 625,377 | 6.57 | 4 hrs 39 mins |
14 | GeForce RTX 3070 Lite Hash Rate GA104 [GeForce RTX 3070 Lite Hash Rate] |
Nvidia | GA104 | 3,911,307 | 609,843 | 6.41 | 4 hrs 45 mins |
15 | Quadro RTX 6000/8000 TU102GL [Quadro RTX 6000/8000] |
Nvidia | TU102GL | 3,768,359 | 607,838 | 6.20 | 4 hrs 52 mins |
16 | GeForce RTX 2080 Rev. A TU104 [GeForce RTX 2080 Rev. A] 10068 |
Nvidia | TU104 | 3,580,698 | 596,754 | 6.00 | 4 hrs 60 mins |
17 | Tesla P100 16GB GP100GL [Tesla P100 16GB] 9340 |
Nvidia | GP100GL | 3,216,408 | 576,267 | 5.58 | 4 hrs 18 mins |
18 | TITAN X GP102 [TITAN X] 6144 |
Nvidia | GP102 | 3,205,384 | 573,094 | 5.59 | 4 hrs 17 mins |
19 | GeForce RTX 2070 SUPER TU104 [GeForce RTX 2070 SUPER] 8218 |
Nvidia | TU104 | 3,071,550 | 567,379 | 5.41 | 4 hrs 26 mins |
20 | GeForce RTX 3060 Ti GA104 [GeForce RTX 3060 Ti] |
Nvidia | GA104 | 2,955,398 | 566,746 | 5.21 | 5 hrs 36 mins |
21 | GeForce RTX 3060 Ti Lite Hash Rate GA104 [GeForce RTX 3060 Ti Lite Hash Rate] |
Nvidia | GA104 | 2,952,937 | 561,509 | 5.26 | 5 hrs 34 mins |
22 | GeForce RTX 2080 Super TU104 [GeForce RTX 2080 SUPER] |
Nvidia | TU104 | 2,777,923 | 552,977 | 5.02 | 5 hrs 47 mins |
23 | Radeon RX 6900 XT Navi 21 [Radeon RX 6900 XT] |
AMD | Navi 21 | 2,749,695 | 546,297 | 5.03 | 5 hrs 46 mins |
24 | GeForce RTX 2070 Rev. A TU106 [GeForce RTX 2070 Rev. A] |
Nvidia | TU106 | 2,729,925 | 547,360 | 4.99 | 5 hrs 49 mins |
25 | GeForce RTX 2060 Super TU106 [GeForce RTX 2060 SUPER] |
Nvidia | TU106 | 2,451,135 | 531,386 | 4.61 | 5 hrs 12 mins |
26 | GeForce RTX 3070 Mobile / Max-Q GA104M [GeForce RTX 3070 Mobile / Max-Q] |
Nvidia | GA104M | 2,386,693 | 451,251 | 5.29 | 5 hrs 32 mins |
27 | GeForce RTX 3080 Mobile / Max-Q 8GB/16GB GA104M [GeForce RTX 3080 Mobile / Max-Q 8GB/16GB] |
Nvidia | GA104M | 2,341,312 | 483,117 | 4.85 | 5 hrs 57 mins |
28 | GeForce RTX 3060 GA106 [GeForce RTX 3060] |
Nvidia | GA106 | 2,335,627 | 519,356 | 4.50 | 5 hrs 20 mins |
29 | GeForce RTX 2070 TU106 [GeForce RTX 2070] |
Nvidia | TU106 | 2,244,898 | 515,258 | 4.36 | 6 hrs 31 mins |
30 | GeForce RTX 3060 GA104 [GeForce RTX 3060] |
Nvidia | GA104 | 2,187,505 | 506,907 | 4.32 | 6 hrs 34 mins |
31 | Quadro RTX 4000 TU104GL [Quadro RTX 4000] |
Nvidia | TU104GL | 2,090,162 | 499,052 | 4.19 | 6 hrs 44 mins |
32 | Radeon VII Vega 20 [Radeon VII] 13,284 |
AMD | Vega 20 | 2,065,275 | 474,796 | 4.35 | 6 hrs 31 mins |
33 | Radeon RX 6700/6700 XT/6750 XT / 6800M Navi 22 [Radeon RX 6700/6700 XT/6750 XT / 6800M] |
AMD | Navi 22 | 2,017,856 | 478,258 | 4.22 | 6 hrs 41 mins |
34 | GeForce GTX 1080 Ti GP102 [GeForce GTX 1080 Ti] 11380 |
Nvidia | GP102 | 1,930,135 | 495,725 | 3.89 | 6 hrs 10 mins |
35 | Radeon RX 6650 XT Navi 23 [Radeon RX 6650 XT] |
AMD | Navi 23 | 1,901,949 | 481,647 | 3.95 | 6 hrs 5 mins |
36 | Geforce RTX 3070 Ti Laptop GPU GA104 [Geforce RTX 3070 Ti Laptop GPU] |
Nvidia | GA104 | 1,854,595 | 371,931 | 4.99 | 5 hrs 49 mins |
37 | GeForce RTX 3060 Lite Hash Rate GA106 [GeForce RTX 3060 Lite Hash Rate] |
Nvidia | GA106 | 1,847,933 | 485,662 | 3.80 | 6 hrs 18 mins |
38 | GeForce RTX 3060 Mobile / Max-Q GA106M [GeForce RTX 3060 Mobile / Max-Q] |
Nvidia | GA106M | 1,758,335 | 449,772 | 3.91 | 6 hrs 8 mins |
39 | Radeon RX 6600/6600 XT/6600M Navi 23 [Radeon RX 6600/6600 XT/6600M] |
AMD | Navi 23 | 1,714,508 | 462,134 | 3.71 | 6 hrs 28 mins |
40 | GeForce RTX 2060 TU106 [Geforce RTX 2060] |
Nvidia | TU106 | 1,683,421 | 448,688 | 3.75 | 6 hrs 24 mins |
41 | Radeon PRO W6600 Navi 23 WKS-XL [Radeon PRO W6600] |
AMD | Navi 23 WKS-XL | 1,630,283 | 454,150 | 3.59 | 7 hrs 41 mins |
42 | GeForce RTX 2070 Mobile / Max-Q Refresh TU106M [GeForce RTX 2070 Mobile / Max-Q Refresh] |
Nvidia | TU106M | 1,501,689 | 474,704 | 3.16 | 8 hrs 35 mins |
43 | GeForce RTX 2060 Mobile / Max-Q TU106M [GeForce RTX 2060 Mobile / Max-Q] |
Nvidia | TU106M | 1,270,942 | 425,564 | 2.99 | 8 hrs 2 mins |
44 | GeForce RTX 2060 TU104 [GeForce RTX 2060] |
Nvidia | TU104 | 1,253,233 | 417,467 | 3.00 | 8 hrs 60 mins |
45 | GeForce GTX 1660 Mobile TU116M [GeForce GTX 1660 Mobile] |
Nvidia | TU116M | 1,198,399 | 415,413 | 2.88 | 8 hrs 19 mins |
46 | GeForce GTX 1660 SUPER TU116 [GeForce GTX 1660 SUPER] |
Nvidia | TU116 | 1,174,785 | 418,131 | 2.81 | 9 hrs 33 mins |
47 | GeForce GTX Titan X GM200 [GeForce GTX Titan X] 6144 |
Nvidia | GM200 | 1,160,860 | 448,381 | 2.59 | 9 hrs 16 mins |
48 | GeForce GTX 980 Ti GM200 [GeForce GTX 980 Ti] 5632 |
Nvidia | GM200 | 1,143,800 | 381,268 | 3.00 | 8 hrs 0 mins |
49 | GeForce GTX 1070 Ti GP104 [GeForce GTX 1070 Ti] 8186 |
Nvidia | GP104 | 1,123,690 | 394,738 | 2.85 | 8 hrs 26 mins |
50 | Radeon RX 5600 OEM/5600 XT/5700/5700 XT Navi 10 [Radeon RX 5600 OEM/5600 XT/5700/5700 XT] |
AMD | Navi 10 | 1,099,958 | 392,308 | 2.80 | 9 hrs 34 mins |
51 | GeForce GTX 1080 GP104 [GeForce GTX 1080] 8873 |
Nvidia | GP104 | 1,097,384 | 422,720 | 2.60 | 9 hrs 15 mins |
52 | Radeon Pro W5700 Navi 10 [Radeon Pro W5700] |
AMD | Navi 10 | 1,091,995 | 424,732 | 2.57 | 9 hrs 20 mins |
53 | GeForce GTX 1070 GP104 [GeForce GTX 1070] 6463 |
Nvidia | GP104 | 1,083,970 | 405,489 | 2.67 | 9 hrs 59 mins |
54 | GeForce GTX 1660 Ti TU116 [GeForce GTX 1660 Ti] |
Nvidia | TU116 | 1,076,977 | 435,318 | 2.47 | 10 hrs 42 mins |
55 | GeForce RTX 3050 Ti Mobile GA107M [GeForce RTX 3050 Ti Mobile] |
Nvidia | GA107M | 1,007,045 | 413,680 | 2.43 | 10 hrs 52 mins |
56 | Radeon Instinct MI25 Vega 10 [Radeon Instinct MI25] |
AMD | Vega 10 | 997,660 | 391,670 | 2.55 | 9 hrs 25 mins |
57 | Tesla M40 GM200GL [Tesla M40] 6844 |
Nvidia | GM200GL | 974,957 | 405,064 | 2.41 | 10 hrs 58 mins |
58 | Radeon RX Vega 56/64 Vega 10 XL/XT [Radeon RX Vega 56/64] |
AMD | Vega 10 XL/XT | 907,476 | 369,811 | 2.45 | 10 hrs 47 mins |
59 | Geforce RTX 3050 GA106 [Geforce RTX 3050] |
Nvidia | GA106 | 890,842 | 383,883 | 2.32 | 10 hrs 21 mins |
60 | GeForce GTX 980 GM204 [GeForce GTX 980] 4612 |
Nvidia | GM204 | 873,575 | 373,567 | 2.34 | 10 hrs 16 mins |
61 | GeForce GTX 1060 6GB GP106 [GeForce GTX 1060 6GB] 4372 |
Nvidia | GP106 | 823,076 | 367,882 | 2.24 | 11 hrs 44 mins |
62 | P104-100 GP104 [P104-100] |
Nvidia | GP104 | 773,115 | 386,196 | 2.00 | 12 hrs 59 mins |
63 | Tesla P4 GP104GL [Tesla P4] 5704 |
Nvidia | GP104GL | 736,698 | 352,135 | 2.09 | 11 hrs 28 mins |
64 | GeForce GTX 1060 3GB GP106 [GeForce GTX 1060 3GB] 3935 |
Nvidia | GP106 | 724,459 | 349,895 | 2.07 | 12 hrs 35 mins |
65 | GeForce GTX 1660 TU116 [GeForce GTX 1660] |
Nvidia | TU116 | 709,586 | 358,046 | 1.98 | 12 hrs 7 mins |
66 | Quadro T1200 Mobile TU117GLM [Quadro T1200 Mobile] |
Nvidia | TU117GLM | 634,677 | 335,632 | 1.89 | 13 hrs 42 mins |
67 | P106-100 GP106 [P106-100] |
Nvidia | GP106 | 602,772 | 368,504 | 1.64 | 15 hrs 40 mins |
68 | Radeon R9 200/300 Series Hawaii [Radeon R9 200/300 Series] |
AMD | Hawaii | 592,587 | 307,846 | 1.92 | 12 hrs 28 mins |
69 | GeForce GTX 1060 Mobile GP106M [GeForce GTX 1060 Mobile] |
Nvidia | GP106M | 580,385 | 315,857 | 1.84 | 13 hrs 4 mins |
70 | GeForce GTX 1650 SUPER TU116 [GeForce GTX 1650 SUPER] |
Nvidia | TU116 | 574,790 | 343,619 | 1.67 | 14 hrs 21 mins |
71 | Quadro P2200 GP106GL [Quadro P2200] |
Nvidia | GP106GL | 567,851 | 310,227 | 1.83 | 13 hrs 7 mins |
72 | GeForce RTX 2060 Mobile TU106M [GeForce RTX 2060 Mobile] |
Nvidia | TU106M | 555,199 | 319,413 | 1.74 | 14 hrs 48 mins |
73 | Radeon R9 Fury X Fiji XT [Radeon R9 Fury X] |
AMD | Fiji XT | 548,263 | 253,398 | 2.16 | 11 hrs 6 mins |
74 | Radeon RX 470/480/570/580/590 Ellesmere XT [Radeon RX 470/480/570/580/590] |
AMD | Ellesmere XT | 537,423 | 324,737 | 1.65 | 15 hrs 30 mins |
75 | Radeon RX 5500/5500M / Pro 5500M Navi 14 [Radeon RX 5500/5500M / Pro 5500M] |
AMD | Navi 14 | 516,271 | 311,224 | 1.66 | 14 hrs 28 mins |
76 | GeForce GTX 1650 Mobile / Max-Q TU117M [GeForce GTX 1650 Mobile / Max-Q] |
Nvidia | TU117M | 483,597 | 313,652 | 1.54 | 16 hrs 34 mins |
77 | GeForce GTX 1650 TU117 [GeForce GTX 1650] |
Nvidia | TU117 | 472,390 | 300,483 | 1.57 | 15 hrs 16 mins |
78 | P106-090 GP106 [P106-090] |
Nvidia | GP106 | 429,755 | 294,906 | 1.46 | 16 hrs 28 mins |
79 | Quadro M4000 GM204GL [Quadro M4000] |
Nvidia | GM204GL | 387,858 | 284,994 | 1.36 | 18 hrs 38 mins |
80 | GeForce GTX 1050 Ti GP107 [GeForce GTX 1050 Ti] 2138 |
Nvidia | GP107 | 380,860 | 300,650 | 1.27 | 19 hrs 57 mins |
81 | GeForce GTX 980M GM204 [GeForce GTX 980M] 3189 |
Nvidia | GM204 | 378,024 | 273,291 | 1.38 | 17 hrs 21 mins |
82 | GeForce GTX 960 GM206 [GeForce GTX 960] 2308 |
Nvidia | GM206 | 363,710 | 277,846 | 1.31 | 18 hrs 20 mins |
83 | GeForce GTX 950 GM206 [GeForce GTX 950] 1572 |
Nvidia | GM206 | 286,084 | 256,477 | 1.12 | 22 hrs 31 mins |
84 | GeForce GTX 970 GM204 [GeForce GTX 970] 3494 |
Nvidia | GM204 | 269,466 | 268,083 | 1.01 | 24 hrs 53 mins |
85 | GeForce GTX 1050 LP GP107 [GeForce GTX 1050 LP] 1862 |
Nvidia | GP107 | 262,891 | 272,477 | 0.96 | 25 hrs 53 mins |
86 | Radeon RX Vega M XL [Radeon RX Vega M XL] |
AMD | Vega | 250,714 | 244,124 | 1.03 | 23 hrs 22 mins |
87 | Quadro P1000 GP107GL [Quadro P1000] |
Nvidia | GP107GL | 198,767 | 218,362 | 0.91 | 26 hrs 22 mins |
88 | Radeon HD 7800 Series Pitcairn PRO [Radeon HD 7800 Series] |
AMD | Pitcairn PRO | 194,960 | 200,000 | 0.97 | 25 hrs 37 mins |
89 | Radeon Pro WX 5100 Ellesmere Pro [Radeon Pro WX 5100] 122 |
AMD | Ellesmere Pro | 181,830 | 200,000 | 0.91 | 26 hrs 24 mins |
90 | GeForce GTX 750 Ti GM107 [GeForce GTX 750 Ti] 1389 |
Nvidia | GM107 | 160,451 | 200,000 | 0.80 | 30 hrs 55 mins |
91 | Quadro P620 GP107GL [Quadro P620] |
Nvidia | GP107GL | 135,884 | 200,000 | 0.68 | 35 hrs 19 mins |
92 | GeForce GT 1030 GP108 [GeForce GT 1030] |
Nvidia | GP108 | 133,800 | 200,000 | 0.67 | 36 hrs 52 mins |
93 | Radeon HD 7800 Pitcairn [Radeon HD 7800] |
AMD | Pitcairn | 124,573 | 200,000 | 0.62 | 39 hrs 32 mins |
94 | Quadro K2200 GM107GL [Quadro K2200] |
Nvidia | GM107GL | 123,717 | 200,000 | 0.62 | 39 hrs 48 mins |
95 | GeForce MX450 TU117M [GeForce MX450] |
Nvidia | TU117M | 121,565 | 200,000 | 0.61 | 39 hrs 29 mins |
96 | Quadro M2000 GM206GL [Quadro M2000] |
Nvidia | GM206GL | 119,302 | 200,000 | 0.60 | 40 hrs 14 mins |
97 | Radeon R9 200 Series Hawaii [Radeon R9 200 Series] |
AMD | Hawaii | 108,476 | 200,000 | 0.54 | 44 hrs 15 mins |
98 | GeForce GTX 650 Ti GK106 [GeForce GTX 650 Ti] |
Nvidia | GK106 | 101,792 | 200,000 | 0.51 | 47 hrs 9 mins |
99 | Radeon WX 3100 [Radeon WX 3100] |
AMD | 99,643 | 200,000 | 0.50 | 48 hrs 10 mins | |
100 | Quadro K1200 GM107GL [Quadro K1200] |
Nvidia | GM107GL | 93,319 | 200,000 | 0.47 | 51 hrs 26 mins |
101 | Radeon PRO WX3100 Lexa XT [Radeon PRO WX3100] |
AMD | Lexa XT | 82,663 | 200,000 | 0.41 | 58 hrs 4 mins |
102 | Quadro P400 GP107GL [Quadro P400] |
Nvidia | GP107GL | 76,652 | 200,000 | 0.38 | 63 hrs 37 mins |
103 | Quadro K620 GM107GL [Quadro K620] |
Nvidia | GM107GL | 61,925 | 200,000 | 0.31 | 78 hrs 31 mins |
104 | Radeon APU A4-6000 R2 Mullins [Radeon APU A4-6000 R2] |
AMD | Mullins | 13,955 | 200,000 | 0.07 | 344 hrs 58 mins |
PROJECT FOLDING PPD AVERAGES BY CPU BETA
PPDDB data as of Tuesday, 07 February 2023 06:14:50
Rank Project |
CPU Model |
Logical Processors (LP) |
PPD-PLP AVG PPD per 1 LP |
ALL LP-PPD (Estimated) |
Make |
---|