Dear participants,

as target # 22 is almost finished, we are glad to introduce the next target. Most of you have voted for Ebolavirus glycoprotein (GP) (174 out of 425 votes, wow!)

The Ebola virus is a highly virulent pathogen responsible for causing Ebola hemorrhagic fever, a severe and often fatal disease. A key factor in the virus's ability to infect host cells and cause disease is its surface glycoprotein (GP), making it an attractive target for antiviral drug development. The Ebola GP is a trimeric protein composed of two subunits per monomer: GP1, responsible for receptor binding, and GP2, which mediates fusion between the viral and host cell membranes. Initially synthesized as a precursor protein, the GP is cleaved by host proteases (furin, cathepsin) into its functional subunits, a process essential for its role in mediating viral entry. The GP facilitates the virus's attachment to the host cell surface, followed by conformational changes that enable membrane fusion, allowing the virus to enter the host cell (to the host endosomal Niemann-Pick C1 (NPC1) receptor or via direct membrane binding; Vaknin et al.; ACS Infect. Dis. 2024, 10, 5, 1590–1601).

Targeting the GP for drug development is advantageous due to its essential role in viral infection, its highly conserved structure among different Ebola virus strains, and the availability of specific binding cavities that can accommodate small-molecule inhibitors. Structural studies using techniques such as X-ray crystallography have identified these binding cavities and elucidated the GP's conformation in both its free and inhibited states. These insights enable the design of drugs that can specifically bind to and inhibit the GP by stabilizing it in its pre-fusion conformation or interfering with its cleavage, thereby preventing the necessary conformational changes for membrane fusion. We will employ high-resolution structures to conduct virtual screening experiments coupled to molecular dynamics simulations to ultimately identify potential GP inhibitors/modulators.

Promising compounds identified through these computational methods will hopefully undergo further validation using biochemical assays, pseudovirus entry assays, and structural analyses to confirm their inhibitory activity. Targeting the GP offers specificity, as it minimizes off-target effects on host cells and reduces the likelihood of resistance development. Moreover, due to the conserved nature of the GP, drugs targeting it could be effective against multiple Ebola virus strains and variants.

We hope that our computations will contribute to the fight against Ebola!

We will employ high-resolution structures to conduct virtual screening experiments coupled to molecular dynamics simulations to ultimately identify potential GP inhibitors/modulators.

Does the portion of the molecular dynamics simulations use GPU or CPU or combination of both? From what I understand in another molecular dynamics simulation of protein folding project (e.g. folding@home), it has both cpu and gpu applications.

If the task has a long run time using cpu, crunching with gpu will speed up the computation time. Current target #22 tasks already taken a very long time already. If target #23 deals with small atoms molecules size, cpu will probably be ok (again at least from what I understand in folding@home).

Edit: World community grid (WCG) open pandemics project used to have both cpu and gpu applications but later dropped the cpu application because gpu can do more work much faster.

Edit 2: If gpu application requires a lot of coding resources perhaps explore the multi-threaded application within cpu. It's quite common nowadays such as again in folding@home where the project offers cpu multi-threaded application (you can specify how many cores/threads that you want to run), in the area of astrophysics such as milkyway@home or in mathematics such as primegrid.com & amicable_numbers@home. Just throwing out ideas here.

Dear participants,

as target # 22 is almost finished, we are glad to introduce the next target. Most of you have voted for Ebolavirus glycoprotein (GP) (174 out of 425 votes, wow!)

We hope that our computations will contribute to the fight against Ebola!

Will it have a new app name ie EVGP as opposed to short or long or Boinc + zipped?

Interesting information, thanks for the details.

It is true that naming of applications is quite unconventional in this project... I never quite understood why functionality like zipping parameters or having checkpoints would justify different application names...

What is the estimation of the end date of corona_RdRp_v2 ?

What is the estimation of the end date of corona_RdRp_v2 ?

when all the work has been sent out and returned, as for what date that will be I have no idea will depend on how many people work on this project

TN-Grid was able to do it.
https://web.archive.org/web/20230101144605/https://gene.disi.unitn.it/test/gene_science.php

What is the estimation of the end date of corona_RdRp_v2 ?

One or two months, I expect.

Hello! Sample workunits for target "ebola_GP_v1" issued. They will be followed by a tail of "corona_RdRp_v2" tasks.
Thank you for participation!

Nice to hear that a new subproject is coming up.

Does the portion of the molecular dynamics simulations use GPU or CPU or combination of both? From what I understand in another molecular dynamics simulation of protein folding project (e.g. folding@home), it has both cpu and gpu applications.

I don't think the MD simulations mentioned above by Natalia will be part of the SiDock@home BOINC project part, as there is no MD simulation GPU app. Unfortunately, even the current docking app still could not be recoded to employ GPUs.
Still hoping...

Michael.

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President of Rechenkraft.net - This world's first and largest distributed computing organization. We make those things possible that supercomputers don't.

what is the name of #23 executable and upcoming #24 so i can add to my Process Lasso config x64 windows?

cmdock.exe for #23
same for #24