PROJECT #18005 RESEARCH FOR CANCER
FOLDING PERFORMANCE PROFILE

PROJECT SUMMARY

This project investigates anti-cancer drugs that might overcome drug resistance. The targets considered are major oncogenes like SMARCA2, BRD4, Bcl and BTK. Drug-resistance is a major and unavoidable problem and presently only 20–25NULLof all protein targets are studied. Moreover, the focus of current explorations of targets are their enzymatic functions, while ignoring the functions from their scaffold moiety. Roivant's drug discovery choose to focus on a promising new technology, PROteolysis TArgeting Chimeras (PROTACs) which regulates protein function by degrading target proteins instead of inhibiting them. This method provided more sensitivity to drug-resistant targets, better selectivity, and a greater chance to affect the nonenzymatic functions of targeted proteins. Roivant is leading in the general paradigm shift that looks at the kinetics of reactions instead of binding thermodynamics for its PROTACs drug discovery. Specifically, by understanding the balance between changes of entropy and enthalpy and the competition between a ligand and water molecules in molecular binding, which is known to be crucial for smart drug discovery. Experiments provide measurements, however, computational methods provide information about binding/unbinding processes that allows for a complete picture of molecular recognition not directly available from experiments. All the computed values of kon, koff, ΔH, ΔS, and ΔG use AMBER force fields for Protein-Protein and Protein-Ligand's interactions. The experimental data is used to guide and improve the predictive, modeling tools for PROTAC drug discovery in iterative manner. 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.

This is a project run by Roivant Sciences (formerly Silicon Therapeutics) as was officially announced in this press release: https://foldingathome.org/2021/04/20/maximizing-the-impact-of-foldinghome-by-engaging-industry-collaborators/

PROJECT INFO

Manager(s): Rafal Wiewiora

Institution: Roivant Sciences (Silicon Therapeutics)

Project URL: roivant.com

PROJECT WORK UNIT SUMMARY

Atoms: 80,117

Core: OPENMM_22

Status: Public

PROJECT FOLDING PPD AVERAGES BY GPU

PPDDB data as of Friday, 23 July 2021 12:13:38

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 5,453,267 485,006 11.24 2 hrs 8 mins
2 GeForce RTX 3080 Ti
GA102 [GeForce RTX 3080 Ti]
Nvidia GA102 5,240,426 480,629 10.90 2 hrs 12 mins
3 GeForce RTX 3080
GA102 [GeForce RTX 3080]
Nvidia GA102 4,249,186 452,184 9.40 3 hrs 33 mins
4 Radeon RX 6900 XT
Navi 21 [Radeon RX 6900 XT]
AMD Navi 21 3,851,228 435,787 8.84 3 hrs 43 mins
5 GeForce RTX 2080 Ti Rev. A
TU102 [GeForce RTX 2080 Ti Rev. A] M 13448
Nvidia TU102 3,626,419 426,033 8.51 3 hrs 49 mins
6 GeForce RTX 3070 Ti
GA104 [GeForce RTX 3070 Ti]
Nvidia GA104 2,951,094 397,426 7.43 3 hrs 14 mins
7 GeForce RTX 2080 Ti
TU102 [GeForce RTX 2080 Ti] M 13448
Nvidia TU102 2,812,951 393,357 7.15 3 hrs 21 mins
8 GeForce RTX 3070
GA104 [GeForce RTX 3070]
Nvidia GA104 2,520,219 379,582 6.64 4 hrs 37 mins
9 GeForce RTX 2070 SUPER
TU104 [GeForce RTX 2070 SUPER] 8218
Nvidia TU104 2,453,441 374,422 6.55 4 hrs 40 mins
10 TITAN Xp
GP102 [TITAN Xp] 12150
Nvidia GP102 2,288,432 368,058 6.22 4 hrs 52 mins
11 GeForce RTX 2080 Super
TU104 [GeForce RTX 2080 SUPER]
Nvidia TU104 2,204,758 363,639 6.06 4 hrs 58 mins
12 Radeon RX 6800/6800 XT / 6900 XT
Navi 21 [Radeon RX 6800/6800 XT / 6900 XT]
AMD Navi 21 2,105,873 356,625 5.91 4 hrs 4 mins
13 GeForce RTX 2070 Rev. A
TU106 [GeForce RTX 2070 Rev. A] M 7465
Nvidia TU106 2,044,763 354,571 5.77 4 hrs 10 mins
14 GeForce GTX 1080 Ti
GP102 [GeForce GTX 1080 Ti] 11380
Nvidia GP102 2,011,849 352,211 5.71 4 hrs 12 mins
15 GeForce RTX 2080 Rev. A
TU104 [GeForce RTX 2080 Rev. A] 10068
Nvidia TU104 2,005,128 351,921 5.70 4 hrs 13 mins
16 GeForce RTX 3060 Ti
GA104 [GeForce RTX 3060 Ti]
Nvidia GA104 1,963,025 349,843 5.61 4 hrs 17 mins
17 GeForce RTX 2080
TU104 [GeForce RTX 2080]
Nvidia TU104 1,936,390 348,157 5.56 4 hrs 19 mins
18 GeForce RTX 2060 Super
TU106 [GeForce RTX 2060 SUPER]
Nvidia TU106 1,746,423 334,794 5.22 5 hrs 36 mins
19 Radeon RX 6700/6700 XT / 6800M
Navi 22 [Radeon RX 6700/6700 XT / 6800M]
AMD Navi 22 1,697,606 328,534 5.17 5 hrs 39 mins
20 GeForce RTX 3070 Mobile / Max-Q 8GB/16GB
GA104M [GeForce RTX 3070 Mobile / Max-Q 8GB/16GB]
Nvidia GA104M 1,681,173 331,229 5.08 5 hrs 44 mins
21 GeForce RTX 2060
TU106 [Geforce RTX 2060]
Nvidia TU106 1,534,156 323,167 4.75 5 hrs 3 mins
22 Radeon RX 5600 OEM/5600 XT/5700/5700 XT
Navi 10 [Radeon RX 5600 OEM/5600 XT/5700/5700 XT]
AMD Navi 10 1,352,071 307,469 4.40 5 hrs 27 mins
23 GeForce RTX 3060
GA106 [GeForce RTX 3060]
Nvidia GA106 1,272,580 302,693 4.20 6 hrs 43 mins
24 GeForce GTX 1070 Ti
GP104 [GeForce GTX 1070 Ti] 8186
Nvidia GP104 1,259,930 302,165 4.17 6 hrs 45 mins
25 Quadro P5000
GP104GL [Quadro P5000]
Nvidia GP104GL 1,090,083 287,661 3.79 6 hrs 20 mins
26 GeForce RTX 2070
TU106 [GeForce RTX 2070] M 6497
Nvidia TU106 1,029,663 205,571 5.01 5 hrs 47 mins
27 GeForce GTX 1660 SUPER
TU116 [GeForce GTX 1660 SUPER]
Nvidia TU116 931,613 264,669 3.52 7 hrs 49 mins
28 GeForce GTX 1070
GP104 [GeForce GTX 1070] 6463
Nvidia GP104 792,007 253,317 3.13 8 hrs 41 mins
29 Radeon RX Vega 56/64
Vega 10 XL/XT [Radeon RX Vega 56/64]
AMD Vega 10 XL/XT 766,130 238,828 3.21 7 hrs 29 mins
30 GeForce GTX 1060 6GB
GP106 [GeForce GTX 1060 6GB] 4372
Nvidia GP106 670,882 244,565 2.74 9 hrs 45 mins
31 GeForce GTX 1080
GP104 [GeForce GTX 1080] 8873
Nvidia GP104 610,917 217,116 2.81 9 hrs 32 mins
32 GeForce GTX 1060 3GB
GP106 [GeForce GTX 1060 3GB] 3935
Nvidia GP106 570,633 230,648 2.47 10 hrs 42 mins
33 GeForce GTX 970
GM204 [GeForce GTX 970] 3494
Nvidia GM204 557,205 229,792 2.42 10 hrs 54 mins
34 GeForce GTX 1650
TU116 [GeForce GTX 1650] 2984
Nvidia TU116 460,702 202,648 2.27 11 hrs 33 mins
35 Radeon RX 470/480/570/580/590
Ellesmere XT [Radeon RX 470/480/570/580/590]
AMD Ellesmere XT 423,780 195,154 2.17 11 hrs 3 mins
36 Quadro T2000 Mobile / Max-Q
TU117GLM [Quadro T2000 Mobile / Max-Q]
Nvidia TU117GLM 397,553 204,229 1.95 12 hrs 20 mins
37 GeForce GTX 1650 SUPER
TU116 [GeForce GTX 1650 SUPER]
Nvidia TU116 302,996 120,988 2.50 10 hrs 35 mins
38 GeForce GTX 960
GM206 [GeForce GTX 960] 2308
Nvidia GM206 292,174 185,753 1.57 15 hrs 15 mins
39 GeForce GTX 1050 Mobile
GP107M [GeForce GTX 1050 Mobile]
Nvidia GP107M 267,705 179,566 1.49 16 hrs 6 mins
40 P106-100
GP106 [P106-100]
Nvidia GP106 218,454 149,879 1.46 16 hrs 28 mins
41 GeForce GT 1030
GP108 [GeForce GT 1030] 1127
Nvidia GP108 91,889 120,988 0.76 32 hrs 36 mins

PROJECT FOLDING PPD AVERAGES BY CPU BETA

PPDDB data as of Friday, 23 July 2021 12:13:38

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