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: OPENMM_22

Status: Public

PROJECT FOLDING PPD AVERAGES BY GPU

PPDDB data as of Sunday, 02 October 2022 12:16:26

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 Ti
GA102 [GeForce RTX 3090 Ti]
Nvidia GA102 8,452,442 795,379 10.63 2 hrs 16 mins
2 GeForce RTX 3090
GA102 [GeForce RTX 3090]
Nvidia GA102 7,878,810 766,243 10.28 2 hrs 20 mins
3 GeForce RTX 3080 Ti
GA102 [GeForce RTX 3080 Ti]
Nvidia GA102 7,359,964 764,796 9.62 2 hrs 30 mins
4 GeForce RTX 3080 12GB
GA102 [GeForce RTX 3080 12GB]
Nvidia GA102 6,962,187 712,986 9.76 2 hrs 27 mins
5 GeForce RTX 3080 Lite Hash Rate
GA102 [GeForce RTX 3080 Lite Hash Rate]
Nvidia GA102 6,502,397 724,176 8.98 3 hrs 40 mins
6 Radeon RX 6950 XT
Navi 21 [Radeon RX 6950 XT]
AMD Navi 21 5,879,197 708,193 8.30 3 hrs 53 mins
7 GeForce RTX 3080
GA102 [GeForce RTX 3080]
Nvidia GA102 5,728,387 688,327 8.32 3 hrs 53 mins
8 GeForce RTX 2080 Ti Rev. A
TU102 [GeForce RTX 2080 Ti Rev. A] M 13448
Nvidia TU102 5,179,074 674,251 7.68 3 hrs 7 mins
9 GeForce RTX 2080 Ti
TU102 [GeForce RTX 2080 Ti] M 13448
Nvidia TU102 5,170,953 674,251 7.67 3 hrs 8 mins
10 Radeon RX 6800/6800 XT / 6900 XT
Navi 21 [Radeon RX 6800/6800 XT / 6900 XT]
AMD Navi 21 4,604,463 642,075 7.17 3 hrs 21 mins
11 GeForce RTX 3070 Ti
GA104 [GeForce RTX 3070 Ti]
Nvidia GA104 4,416,575 634,379 6.96 3 hrs 27 mins
12 GeForce RTX 3070 Lite Hash Rate
GA104 [GeForce RTX 3070 Lite Hash Rate]
Nvidia GA104 4,141,982 622,188 6.66 4 hrs 36 mins
13 GeForce RTX 3070
GA104 [GeForce RTX 3070]
Nvidia GA104 3,991,134 622,704 6.41 4 hrs 45 mins
14 GeForce RTX 2080 Rev. A
TU104 [GeForce RTX 2080 Rev. A] 10068
Nvidia TU104 3,486,331 593,120 5.88 4 hrs 5 mins
15 Tesla P100 16GB
GP100GL [Tesla P100 16GB] 9340
Nvidia GP100GL 3,216,408 576,267 5.58 4 hrs 18 mins
16 TITAN X
GP102 [TITAN X] 6144
Nvidia GP102 3,203,605 575,663 5.57 4 hrs 19 mins
17 GeForce RTX 3070 Mobile / Max-Q
GA104M [GeForce RTX 3070 Mobile / Max-Q]
Nvidia GA104M 3,110,416 580,944 5.35 4 hrs 29 mins
18 GeForce RTX 2080 Super
TU104 [GeForce RTX 2080 SUPER]
Nvidia TU104 3,100,935 573,945 5.40 4 hrs 27 mins
19 GeForce RTX 3060 Ti
GA104 [GeForce RTX 3060 Ti]
Nvidia GA104 2,955,398 566,746 5.21 5 hrs 36 mins
20 GeForce RTX 3060 Ti Lite Hash Rate
GA104 [GeForce RTX 3060 Ti Lite Hash Rate]
Nvidia GA104 2,936,673 558,441 5.26 5 hrs 34 mins
21 Radeon RX 6900 XT
Navi 21 [Radeon RX 6900 XT]
AMD Navi 21 2,749,695 546,297 5.03 5 hrs 46 mins
22 GeForce RTX 2070 Rev. A
TU106 [GeForce RTX 2070 Rev. A]
Nvidia TU106 2,729,925 547,360 4.99 5 hrs 49 mins
23 GeForce RTX 2070 SUPER
TU104 [GeForce RTX 2070 SUPER] 8218
Nvidia TU104 2,575,472 533,202 4.83 5 hrs 58 mins
24 GeForce RTX 2060 Super
TU106 [GeForce RTX 2060 SUPER]
Nvidia TU106 2,408,414 527,153 4.57 5 hrs 15 mins
25 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
26 Radeon VII
Vega 20 [Radeon VII] 13,284
AMD Vega 20 2,334,908 474,202 4.92 5 hrs 52 mins
27 GeForce RTX 3060
GA104 [GeForce RTX 3060]
Nvidia GA104 2,186,341 504,066 4.34 6 hrs 32 mins
28 Radeon RX 6600/6600 XT/6600M
Navi 23 [Radeon RX 6600/6600 XT/6600M]
AMD Navi 23 2,123,367 501,088 4.24 6 hrs 40 mins
29 GeForce GTX 1080 Ti
GP102 [GeForce GTX 1080 Ti] 11380
Nvidia GP102 2,090,015 506,249 4.13 6 hrs 49 mins
30 Quadro RTX 4000
TU104GL [Quadro RTX 4000]
Nvidia TU104GL 2,082,978 498,450 4.18 6 hrs 45 mins
31 GeForce RTX 2070
TU106 [GeForce RTX 2070]
Nvidia TU106 2,046,349 484,976 4.22 6 hrs 41 mins
32 GeForce RTX 3060 Mobile / Max-Q
GA106M [GeForce RTX 3060 Mobile / Max-Q]
Nvidia GA106M 1,941,907 474,612 4.09 6 hrs 52 mins
33 Radeon RX 6700/6700 XT/6750 XT / 6800M
Navi 22 [Radeon RX 6700/6700 XT/6750 XT / 6800M]
AMD Navi 22 1,849,894 463,151 3.99 6 hrs 1 mins
34 GeForce RTX 3060 Lite Hash Rate
GA106 [GeForce RTX 3060 Lite Hash Rate]
Nvidia GA106 1,834,427 481,134 3.81 6 hrs 18 mins
35 GeForce RTX 2060
TU106 [Geforce RTX 2060]
Nvidia TU106 1,717,428 453,663 3.79 6 hrs 20 mins
36 Radeon PRO W6600
Navi 23 WKS-XL [Radeon PRO W6600]
AMD Navi 23 WKS-XL 1,654,760 462,413 3.58 7 hrs 42 mins
37 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
38 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
39 GeForce RTX 2060
TU104 [GeForce RTX 2060]
Nvidia TU104 1,253,233 417,467 3.00 8 hrs 60 mins
40 GeForce GTX 1080
GP104 [GeForce GTX 1080] 8873
Nvidia GP104 1,179,339 428,660 2.75 9 hrs 43 mins
41 GeForce GTX Titan X
GM200 [GeForce GTX Titan X] 6144
Nvidia GM200 1,160,860 448,381 2.59 9 hrs 16 mins
42 Radeon RX 5600 OEM/5600 XT/5700/5700 XT
Navi 10 [Radeon RX 5600 OEM/5600 XT/5700/5700 XT]
AMD Navi 10 1,157,313 395,447 2.93 8 hrs 12 mins
43 GeForce GTX 1070 Ti
GP104 [GeForce GTX 1070 Ti] 8186
Nvidia GP104 1,133,902 394,589 2.87 8 hrs 21 mins
44 GeForce GTX 1660 Ti
TU116 [GeForce GTX 1660 Ti]
Nvidia TU116 1,113,979 436,397 2.55 9 hrs 24 mins
45 GeForce GTX 1660 SUPER
TU116 [GeForce GTX 1660 SUPER]
Nvidia TU116 1,113,378 402,399 2.77 9 hrs 40 mins
46 Radeon Pro W5700
Navi 10 [Radeon Pro W5700]
AMD Navi 10 1,112,498 423,963 2.62 9 hrs 9 mins
47 GeForce GTX 980 Ti
GM200 [GeForce GTX 980 Ti] 5632
Nvidia GM200 1,111,691 376,423 2.95 8 hrs 8 mins
48 GeForce GTX 1070
GP104 [GeForce GTX 1070] 6463
Nvidia GP104 1,074,400 405,466 2.65 9 hrs 3 mins
49 Tesla M40
GM200GL [Tesla M40] 6844
Nvidia GM200GL 1,064,942 402,659 2.64 9 hrs 4 mins
50 Radeon Instinct MI25
Vega 10 [Radeon Instinct MI25]
AMD Vega 10 997,660 391,670 2.55 9 hrs 25 mins
51 Geforce RTX 3050
GA106 [Geforce RTX 3050]
Nvidia GA106 882,651 380,150 2.32 10 hrs 20 mins
52 Radeon RX Vega 56/64
Vega 10 XL/XT [Radeon RX Vega 56/64]
AMD Vega 10 XL/XT 864,353 368,526 2.35 10 hrs 14 mins
53 GeForce GTX 980
GM204 [GeForce GTX 980] 4612
Nvidia GM204 842,481 368,253 2.29 10 hrs 29 mins
54 GeForce GTX 1060 6GB
GP106 [GeForce GTX 1060 6GB] 4372
Nvidia GP106 814,347 366,796 2.22 11 hrs 49 mins
55 P104-100
GP104 [P104-100]
Nvidia GP104 773,115 386,196 2.00 12 hrs 59 mins
56 Tesla P4
GP104GL [Tesla P4] 5704
Nvidia GP104GL 736,698 352,135 2.09 11 hrs 28 mins
57 GeForce GTX 1060 3GB
GP106 [GeForce GTX 1060 3GB] 3935
Nvidia GP106 724,459 349,895 2.07 12 hrs 35 mins
58 GeForce GTX 1660
TU116 [GeForce GTX 1660]
Nvidia TU116 709,973 358,139 1.98 12 hrs 6 mins
59 Quadro T1200 Mobile
TU117GLM [Quadro T1200 Mobile]
Nvidia TU117GLM 634,677 335,632 1.89 13 hrs 42 mins
60 P106-100
GP106 [P106-100]
Nvidia GP106 602,845 368,362 1.64 15 hrs 40 mins
61 GeForce GTX 1650 SUPER
TU116 [GeForce GTX 1650 SUPER]
Nvidia TU116 575,980 344,570 1.67 14 hrs 21 mins
62 GeForce GTX 1060 Mobile
GP106M [GeForce GTX 1060 Mobile]
Nvidia GP106M 558,497 310,473 1.80 13 hrs 21 mins
63 GeForce RTX 2060 Mobile
TU106M [GeForce RTX 2060 Mobile]
Nvidia TU106M 555,199 319,413 1.74 14 hrs 48 mins
64 Radeon R9 Fury X
Fiji XT [Radeon R9 Fury X]
AMD Fiji XT 548,263 253,398 2.16 11 hrs 6 mins
65 Radeon RX 470/480/570/580/590
Ellesmere XT [Radeon RX 470/480/570/580/590]
AMD Ellesmere XT 524,667 302,458 1.73 14 hrs 50 mins
66 GeForce GTX 1650
TU117 [GeForce GTX 1650]
Nvidia TU117 472,390 300,483 1.57 15 hrs 16 mins
67 GeForce GTX 1650 Mobile / Max-Q
TU117M [GeForce GTX 1650 Mobile / Max-Q]
Nvidia TU117M 450,290 302,566 1.49 16 hrs 8 mins
68 P106-090
GP106 [P106-090]
Nvidia GP106 435,048 296,079 1.47 16 hrs 20 mins
69 Quadro M4000
GM204GL [Quadro M4000]
Nvidia GM204GL 387,858 284,994 1.36 18 hrs 38 mins
70 GeForce GTX 1050 Ti
GP107 [GeForce GTX 1050 Ti] 2138
Nvidia GP107 377,485 284,708 1.33 18 hrs 6 mins
71 GeForce GTX 980M
GM204 [GeForce GTX 980M] 3189
Nvidia GM204 350,906 263,368 1.33 18 hrs 1 mins
72 Radeon RX 5500/5500M / Pro 5500M
Navi 14 [Radeon RX 5500/5500M / Pro 5500M]
AMD Navi 14 309,642 267,737 1.16 21 hrs 45 mins
73 GeForce GTX 950
GM206 [GeForce GTX 950] 1572
Nvidia GM206 287,292 257,797 1.11 22 hrs 32 mins
74 GeForce GTX 970
GM204 [GeForce GTX 970] 3494
Nvidia GM204 269,466 268,083 1.01 24 hrs 53 mins
75 Radeon RX Vega M XL
[Radeon RX Vega M XL]
AMD Vega 247,948 241,962 1.02 23 hrs 25 mins
76 GeForce GTX 1050 LP
GP107 [GeForce GTX 1050 LP] 1862
Nvidia GP107 239,090 266,409 0.90 27 hrs 45 mins
77 Radeon HD 7800 Series
Pitcairn PRO [Radeon HD 7800 Series]
AMD Pitcairn PRO 194,960 200,000 0.97 25 hrs 37 mins
78 Quadro P1000
GP107GL [Quadro P1000]
Nvidia GP107GL 189,154 213,899 0.88 27 hrs 8 mins
79 Radeon Pro WX 5100
Ellesmere Pro [Radeon Pro WX 5100] 122
AMD Ellesmere Pro 181,830 200,000 0.91 26 hrs 24 mins
80 GeForce GTX 750 Ti
GM107 [GeForce GTX 750 Ti] 1389
Nvidia GM107 160,451 200,000 0.80 30 hrs 55 mins
81 Quadro P620
GP107GL [Quadro P620]
Nvidia GP107GL 135,831 200,000 0.68 35 hrs 20 mins
82 GeForce GT 1030
GP108 [GeForce GT 1030]
Nvidia GP108 133,800 200,000 0.67 36 hrs 52 mins
83 Quadro K2200
GM107GL [Quadro K2200]
Nvidia GM107GL 123,472 200,000 0.62 39 hrs 53 mins
84 Quadro M2000
GM206GL [Quadro M2000]
Nvidia GM206GL 119,302 200,000 0.60 40 hrs 14 mins
85 Radeon R9 200 Series
Hawaii [Radeon R9 200 Series]
AMD Hawaii 108,802 200,000 0.54 44 hrs 7 mins
86 Quadro K1200
GM107GL [Quadro K1200]
Nvidia GM107GL 94,691 200,000 0.47 51 hrs 41 mins
87 Quadro P400
GP107GL [Quadro P400]
Nvidia GP107GL 76,652 200,000 0.38 63 hrs 37 mins
88 Quadro K620
GM107GL [Quadro K620]
Nvidia GM107GL 71,267 200,000 0.36 67 hrs 21 mins

PROJECT FOLDING PPD AVERAGES BY CPU BETA

PPDDB data as of Sunday, 02 October 2022 12:16:26

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