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Targeting the HIV Virus: Researchers Use Supercomputer to Solve the Structure of the HIV-1 Capsid

December 18, 2019

[MUSIC] The threat of HIV has led to an enormous amount
of information on virus infection in general, and in particular on the architecture of the
HIV virus and of the various steps that it undergoes in living cells. There are several therapies that have been
developed over the years against HIV. The problem with those therapies is that for every
single therapy that was developed, the HIV became immune to that therapy. So that is
why people have to go to from one drug to another when they are infected with HIV. A virus that infects a cell contains, at the
core of it, genetic material it tries to smuggle into the cell. And this genetic material is
packaged in what is called the capsid. That capsid is a very strong container for this
genetic material, to protect it as long as the virus is outside of the cell. But once
the virus enters the cell and has infected the cell, then the capsid has to be a very
quickly opening container on the other side. If you want to chemically attack the capsid
for medical reasons, then you need to know the full chemical detail of the capsid. And
that was not available when the project started. So before that we knew it was a polymorphic
structure. So we knew that two of them are going to be different. Then we knew the building
blocks. So we knew that it was made of pentamers and hexamers. But all that information was
known of isolated parts. We did not have the whole structure together. In experiments we
have different techniques that can look at the same thing at different size scales and
at different resolutions. You can look at great detail. And you can look in the physiological
conditions of the proteins. But you can only look at really small pieces of them. You cannot
look at the whole assembly. Then the people who do electronmicroscopy,
they can look at large assemblies at low resolutions. But you cannot see what each atom is doing.
So we have to find a way of putting all of this together to build the capsid. We taught our computer program, over many
decades, how to simulate the macromolecules of the living cell. And so now ,what the computer
can do is, it can try to take the pictures of the individual proteins that you see very
clearly, and match them into these fuzzy images of the proteins that appear with the electronmicroscope. So what we do is computational modeling. If
you look at what we do, it might look like a video game. But we actuallyâ what is going
on there is real. It is what you will see if you were able to look through a microscope
at that scale. Essentially what we do is solve Newton’s equations of motion for the system.
But we do this for several thousands of atoms and how they are interacting and we solve
these for several microseconds. The capsid is made actually out of over a
thousand proteins. All together, we had to simulate the system of three million atoms
that made the envelope and, in addition, all the liquid and salt ions, liquid molecules,
water molecules. That gave us, all together, 64 million atoms. And this was, absolutely
by far, a simulation that was never done earlier. But we were very, very fortunate because,
right when this project was developing, the University of Illinois got delivery of the
Blue Waters computer. So Blue Waters is larger, faster… I mean
it was essential to the success of the project. Because it is the only machine where we could
have run a simulation of this size. So we now we had one of the fastest and largest
computers in the world available. And we knew on this computer you could simulate an up
to 100 million atom systems. And so 64 million fit it actually snugly into the computer.
And so we could carry out the necessary simulation. And so we did. We simulated 64 million atoms.
It took us a month. And I will not forget the day that he came
running to me and said, “Klaus! Klaus! Look at it. Look at it.
How beautiful.” And, in fact, it was really, like many important
scientific results are, they are just initially and immediately
beautiful and clear. And so we got here a very lucky outcome of a very difficult computer
simulation. And we could now look, protein by protein, how these, over a thousand proteins,
are capable of realizing a rather wide distribution of local shapes along the surface of the HIV
capsid. And so that gave us, for the first time, the details of the astonishing maliability
of the capsid proteins. Some of our findings are actually key because
you can do a single mutation and you rendered the virus inactive. That means you know in
very small details, you know what is going to happen at large scale. It also gave us first insight into how one
might approach this capsid through pharmacological warfare by developing drugs that might fit
into some of the nooks and crannies and thereby shut the capsid so that it could not release its
genetic content when it was actually infecting a cell. The capsid is really attractive because it
is essential to the survival of the virus. But also it is because… like in monkeys,
monkeys are immune to HIV. And the way they are immune to HIV is by attacking the capsid.
They destroy the capsid once it gets into their cells. So the reason we have never developed
drugs against the HIV-1 capsid is because we did not know what it looked like. So we
essentially are giving, we are giving to the world this capsid that is the platform for
the development of new therapies. And that is why it is so important. [MUSIC]


  • Reply Mario Posso May 29, 2013 at 6:49 pm

    Amazing! Truly amazing!

  • Reply neurokrem1 May 29, 2013 at 7:59 pm

    Thank you.You've really given me hope for humanitu!

  • Reply marijn degen May 29, 2013 at 11:48 pm

    humans seem to get furder

  • Reply TheSOXMania May 30, 2013 at 1:40 am

    All thanks to NVidea for making the GPU that made that simulation possible… you should've used the Titan super computer!!!

  • Reply johnrobot May 30, 2013 at 12:01 pm

    Blue Waters is about 200 yards from the Beckman Institute

  • Reply baseballplayer1251 May 30, 2013 at 2:59 pm

    I know that HI-Viruses are not persons, still I truly hate them.

  • Reply baseballplayer1251 May 30, 2013 at 3:05 pm

    They may be beautiful, but please, destroy these things!

  • Reply oscarrulez007 May 30, 2013 at 5:07 pm

    the quality of the german accent is not amazing as well, but so what, they search for a way to get in control of the HI – Virus ๐Ÿ˜€

  • Reply FindThisWorld May 31, 2013 at 1:38 am

    How do you simulate the capside of a virus when you don't even know how non-living molecules became a living cell resp. self reproducing DNA/RNA? What helps you to know how the molecular structure of the virus cell is when you have no clue of the exact proceses of the RNA of the virus & how it forms his capsude? One very little small step for mankind…

  • Reply Fred Lincoln May 31, 2013 at 3:46 am

    Keep on pushing ๐Ÿ™‚

  • Reply SiriusLuke May 31, 2013 at 8:50 am

    Do you guys think this discovery is worthy for a Nobel Prize? It sounds pretty big to me.

  • Reply Gustavo Parra May 31, 2013 at 12:59 pm

    It sounds pretty big to me too. IMHO it gives access to a whole new world.

  • Reply Joseph Breckenridge May 31, 2013 at 3:16 pm

    We are so lucky to have smart and hard-working people like this among us. I think they are heroes.

  • Reply jimmyheb May 31, 2013 at 7:29 pm

    No matter how big, arduous or long the race, at the end it will be won by taking one step at a time. No matter how 'small'. You sound so negative. Why all the negativity? What they know now, we didn't know the proverbial 'yesterday'. All the stuff you're nagging about will only be discovered by doing research and doing discovery after discovery, even those you so derogatorily call a 'very little small step for mankind', not by sitting there uselessly criticizing.

  • Reply TheSOXMania June 1, 2013 at 5:10 am

    in that case, it makes sense to use Blue Waters, still one hellishly powerful system!!

  • Reply TheSOXMania June 1, 2013 at 5:11 am

    looks like it might be about 99% correct, it is difficult to tell such a small object when the most you could do is a low res image on a microscope or just parts of the virus excluding capsid!

  • Reply onefineline June 2, 2013 at 2:53 am

    What does knowing how non-living molecules become living cells have to do with anything? I don't need to know how an engine works to know how to change the oil.

  • Reply lordoftheflings June 2, 2013 at 7:58 am

    Sirs and Madams that worked on this research, I solute you!

  • Reply Alex Plugaru June 9, 2013 at 5:18 pm

    how do you know that?

  • Reply Anand Gopinath June 24, 2013 at 9:13 am

    Good observation.

  • Reply Julian Lopez August 26, 2013 at 6:58 am

    excellent work

  • Reply Brooke Willis October 16, 2013 at 8:55 pm

    Too bad about the fuzzy sound and musical overlay.

  • Reply gusjeazer July 1, 2014 at 2:36 pm

    HIV is a hoax, just ask kary mullis or peter duesberg

  • Reply Mr. Mohagany October 8, 2014 at 10:54 pm

    I applaud these guys and their dedication. Wish I knew how the monkey immune system attacks the capsid, as he mentioned in the video.ย 

  • Reply Ian Atkinson October 31, 2014 at 8:25 pm

    Targeting the HIV Virus: Researchers Use Supercomputer to Solve the Structure of the HIV-1 Capsid.

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