
Coronavirus Spike Protein Binder Design - jbj
https://fold.it/portal/node/2008926
======
natch
Strange site. The heading implies that they are attempting to design things
that help science, but if you drill in to the pages for "new to fold.it" and
FAQ, it never actually says that any of the results are used by anyone.
Instead it says that it's all a game and the only science goal is to prove
that humans are capable (just like computers) of doing this.

I wonder if this is really all it is, or if the writers of the FAQ are just
myopic about the fact that newcomers don't have the big picture, so they just
forget to mention whether the results are ever used or not, or even
potentially used, or even potentially looked at by anyone who might use them.

Reminds me of how a lot of open source packages, when you go to their about
page, just have a list of recent updates in highly technical language that
assumes the reader is already familiar with the goals of the project.

Sites should not assume that the reader already knows what is going on. In
this case, the "new to fold.it" page is just a bunch of steps for getting
started, with absolutely no overview that makes clear how any of it is all
used. Under "goals" the stated science goal is just to prove that humans can
solve this kind of puzzles. Really odd that teams would give time to this if
it's not having any real effect though, so I suspect I'm missing something?

~~~
astroalex
I happened to work in the lab at the University of Washington that helped
maintain the game as an undergrad. Here's a published scientific article about
the use of Foldit for science:
[https://www.nature.com/articles/nature09304](https://www.nature.com/articles/nature09304)

(I'm not disagreeing that the website is badly designed.)

~~~
natch
Thanks. I’d quibble about the design word... the design is ok; it’s the
wording that is lacking. Or some clear thinking. I mean for all the effort
they are spending on this, it would take like one paragraph or less to clear
things up. It could be fixed with five minutes of effort.

~~~
goldenchrome
Design encompasses everything that people interact with, so words are part of
design. In fact there's a whole discipline called "User Experience Writing".

~~~
natch
Sure, no argument there, although you’re being a bit over picky about
semantics (even more than I was!). But my point stands that this could be
fixed with a single paragraph of text.

------
hditorkeif
This is what antibodies do, right?

How exactly does the body figure out how to configure the variable part of the
antibody so that it binds? Does it just try countless variations until it
finds a match?

Can we take an antibody from a healed person and reverse engineer the binding
protein?

~~~
littlestymaar
> How exactly does the body figure out how to configure the variable part of
> the antibody so that it binds? Does it just try countless variations until
> it finds a match?

Not a biologist but IIRC, the body produces cells with a shuffled sequence of
DNA. Then this specific cell produces one specific variant of antibodies,
located on its surface. At this point the antibody is just a random sequence
that matches with nothing.

If one day a virus (or anything else) happen to match with the antibody
located on the surface of the cell, the cell will then multiply and most of
the new cells will specialize into antibody-producing cells (released in the
body, not remaining on the surface of the cell) and a small amount will not.
The one who aren't producing antibodies are kept in the body for a long time,
and they are here to provide quick specific response next time you meet the
pathogen again (that's where immunity comes from).

So yeah, it's basically brute-force until a matching antibody is found.

------
Aissen
I know it's fun, and I think participative science is such a huge shift in
paradigm … But considering the global impact of coronavirus, I'm wondering if
there shouldn't be a better way to fund this type of endeavor.

Any cloud provider willing to donate compute to researchers?

~~~
moomin
So close, and yet so far...

What you're looking for is a well-funded public health system. And to vote out
politicians that defund healthcare.

~~~
ppf
Public health systems, well-funded or not, are not a cure-all. I'd be curious
to hear if you have any examples - if anything, they are reliant on research
funded by the huge amount of money sloshing around the US healthcare system.
Given a fixed annual budget, a public health system essentially has to decide
what "healthy" or "cured" means, and set some quality of life to cost of
treatment ratio. Some examples: my dad, an incredibly fit ultra-runner,
suddenly found himself unable to run more than a few miles, and was gasping
for air. He was initially told he was fine for his age, and had to fight for
further diagnosis. A close friend of my wife's died of bowel cancer - this is
a known "loophole" in the diagnosis pathways of our public health care system.
Essentially, it was decided that the cost of early diagnosis is too high for
the relatively tiny amount of people who have it, which is why most cases are
found when they are terminal.

~~~
nolongerlowres
I’m sorry to hear about your wife’s friend. But both examples you gave (people
having to fight for further diagnoses of outside-case health problems) are
really common with private healthcare in the United States too - we’ve just
shifted the burden of cost of treatment/quality of life decisions to private
entities who typically are only interested in furthering shareholder value. To
give a personal anecdote as well: A close friend of my wife’s had to fight and
fight to get insurance to cover appointments in order to get her breast cancer
diagnosed.

I would like to understand if the world really does rely on US private-
healthcare funded research - I’ve heard this argument mentioned before and
have always been curious about it.

~~~
AnthonyMouse
> I’m sorry to hear about your wife’s friend. But both examples you gave
> (people having to fight for further diagnoses of outside-case health
> problems) are really common with private healthcare in the United States too
> - we’ve just shifted the burden of cost of treatment/quality of life
> decisions to private entities who typically are only interested in
> furthering shareholder value.

Having a profit motive is only a serious problem when there is insufficient
competition. Otherwise companies that try to make outlandish profits would
lose business to companies that offer better coverage for lower premiums by
taking smaller profits. Insurance company profits are only a single digit
percentage of US healthcare costs; eliminating them wouldn't make a real dent
anyway. (In many cases the "profits" are also unavoidable. For example, if the
insurance carrier owns its building then the internal rents are "profit" but
if you want to replace them you would still need a building and then have to
pay for it from somewhere else. Every dollar you spend on anything is profit
to somebody.)

And a profit motive will in general tend to _lower_ costs, because a company
that can eliminate waste and then charge lower premiums for the same coverage
will get more business and make more money. There are a lot of reasons it
doesn't work out that way for US health insurance, e.g. when it's provided
with employer subsidies under tax incentives it reduces competitive pressure
(employees can't choose another insurer) and the tax incentives reduce price
sensitivity. But a big one is this:

> I would like to understand if the world really does rely on US private-
> healthcare funded research - I’ve heard this argument mentioned before and
> have always been curious about it.

The basis premise behind the patent system is like this. It takes a lot of
money to do R&D and it may not even turn into anything, but once it's public
knowledge, everybody starts making the thing and not just the party who paid
for the R&D. Which makes it a lot more profitable to wait for somebody else to
do R&D and then go into competition with them than to do the R&D yourself, so
then nobody has the incentive to do it. Patents say if you do the work you get
a temporary monopoly on selling the thing to give you some time to recover
your R&D before competition drives down the price.

In principle this allows the market to set the price. If you invent a more
efficient light bulb, you can ask $1000 for one but no one will pay that much
even if you have a monopoly, they'll just buy the old light bulbs. But you
might be able to charge as much of a premium as your light bulb will save in
electricity over the existing ones and still find buyers.

With drugs the incremental value is often very high -- it could save your life
when the alternative is that you die. Which is what you want to happen,
because you want a large financial incentive to do R&D that can save lives.
But then the cost can be really high which makes people want some kind of
insurance.

When you have private insurers in competition with one another, you still
basically have a market. If the drug maker demands a trillion dollars to treat
one patient, any insurance company willing to pay that would have to charge
premiums nobody can afford, and then nobody would buy that insurance and the
drug maker would get no sales. So there is a limit on what they can charge,
but it's still pretty high, because people really want their insurance to
cover those drugs and will strongly prefer insurance carriers that do over
those that don't. And then you get the large financial incentive to do life-
saving R&D as desired.

With a single payer system, that competition between insurers doesn't exist.
If the system refuses to pay the maker's price for a drug, the system can't
lose customers to a competing insurer that will. Which means you have a
monopsony buyer that can dictate prices. Naturally they have the incentive to
dictate prices that are lower. But higher prices during the exclusivity period
is how the patent system directs money to R&D. By dictating lower prices
they're not paying their share of the cost of developing the drugs that only
exist because the US is paying more, and causing some life-saving drugs to not
exist because the US market on its own isn't enough to justify the R&D.

~~~
danaris
> Having a profit motive is only a serious problem when there is insufficient
> competition. Otherwise companies that try to make outlandish profits would
> lose business to companies that offer better coverage for lower premiums by
> taking smaller profits.

This works in an _idealized_ free market.

Health care is, for a variety of reasons, fundamentally incompatible with
this, even if the powerful and wealthy interests within it are not actively
working to destroy some of the basic premises of a free market (like equal
information).

~~~
AnthonyMouse
> This works in an _idealized_ free market.

It works in any kind of market that isn't a dumpster fire. The closer to
idealized it is the better it works, but it still works in real markets that
actually exist. The people who sell towels to Walmart are not an "idealized
free market" but it's close enough for practical purposes.

> Health care is, for a variety of reasons, fundamentally incompatible with
> this, even if the powerful and wealthy interests within it are not actively
> working to destroy some of the basic premises of a free market (like equal
> information).

Health care is not incompatible with it. People place a high value on life-
saving treatment, but that's as it should be. It has a high value. If it costs
a lot to provide or develop, it's worth the cost. The key is to not pay that
cost in cases when it isn't necessary -- but you still want to in cases when
it is.

The state of US health care and insurance regulations, however, are a dumpster
fire. It doesn't have to be like this. The status quo is not optimal.

As you say, even just having real price transparency would mark a significant
improvement.

Fixing that is hard because there are powerful interests behind the status
quo, but the same interests are aligned against a single payer system. You
can't use it as an argument against one and not the other.

~~~
danaris
> The people who sell towels to Walmart are not an "idealized free market" but
> it's close enough for practical purposes.

Towels are a commodity: they're functional, fairly easy to produce, and
differentiation is a pretty straightforward tradeoff of higher price for more
luxury towels.

Health care is not a commodity. Different services are not interchangeable,
and for anything more specialized than basic care, there may only be one
provider within a reasonable distance of you that can offer it _at all_ , let
alone at an acceptable level of quality.

Furthermore, at the point of sale, much of the time, the "customer" is neither
in a condition nor a position to be shopping around. Sometimes, they're
literally unconscious. And while some elective procedures and preventative
visits can be scheduled and planned, emergency care is by definition not
something you can plan ahead for to determine where you can get the best value
for your money.

None of these things are because of the specific sorry state of healthcare in
the US. They are all _fundamental_ to its very nature. It is impossible to
have a truly free market for healthcare, because getting it is _literally_ a
matter of life and death for the _patient_ in many cases, which means that by
the economics of an unregulated market, the provider can charge them literally
whatever they can afford to pay. Or more.

> Fixing that is hard because there are powerful interests behind the status
> quo, but the same interests are aligned against a single payer system. You
> can't use it as an argument against one and not the other.

Great, I completely agree.

So instead of trying to fight for a tiny baby step that will improve the
system by 1%, let's fight the same people for single payer, a meaningful
change that will improve the system by 1000x.

~~~
AnthonyMouse
> Health care is not a commodity. Different services are not interchangeable,
> and for anything more specialized than basic care, there may only be one
> provider within a reasonable distance of you that can offer it _at all_ ,
> let alone at an acceptable level of quality.

In what way is it not a commodity? Does the medical practice in the next town
over not have an X-ray machine or an operating room or whatever it is that you
need? There are very few procedures that can only be done by one provider in
the world.

Reasonable distance is also related to price. If the local provider is asking
$10,000 then a $300 plane ticket to use a provider that charges a quarter of
the price is completely reasonable. Which, if we had meaningful price
transparency, would then prevent the local provider from charging $10,000 to
begin with or else nearly everybody would know to buy the plane ticket and
they would have no patients.

> Furthermore, at the point of sale, much of the time, the "customer" is
> neither in a condition nor a position to be shopping around. Sometimes,
> they're literally unconscious. And while some elective procedures and
> preventative visits can be scheduled and planned, emergency care is by
> definition not something you can plan ahead for to determine where you can
> get the best value for your money.

So have your city provide emergency rooms the same way they provide fire
departments. What does that have to do with the majority of medical care which
is not done on an emergency basis?

> It is impossible to have a truly free market for healthcare, because getting
> it is _literally_ a matter of life and death for the _patient_ in many
> cases, which means that by the economics of an unregulated market, the
> provider can charge them literally whatever they can afford to pay.

Being a matter of life and death doesn't break markets in any way. Markets
operate through competition. It may be _worth_ a million dollars to you to
save your life, but if it only _costs_ $200 then providers will be lining up
to charge $250 and make $50.

Food is a matter of life and death too. Does that mean we should have
socialized farming?

> So instead of trying to fight for a tiny baby step that will improve the
> system by 1%, let's fight the same people for single payer, a meaningful
> change that will improve the system by 1000x.

Because you can get a lot more than 1% improvement from things like price
transparency or addressing existing constraints on the number of new doctors,
which are easier to pass because for each one you only have to fight 10% of
the incumbent apparatus instead of the whole thing aligned together.

Also because single payer doesn't actually solve problems by magic, so you
still have to solve each of the individual problems anyway. If the FDA
approval process continues to be very expensive and thereby causes drugs to
only come to market when they're expected to be very profitable, how is single
payer supposed to reduce drug prices without reducing the number of new drugs?
How does it address the de facto limits on the number of new doctors? They're
still independent problems.

~~~
danaris
Your answers talking about taking plane trips to get to other providers show
that you are only considering the effects of these things on the fairly-well-
off and up, and completely ignoring how they affect the poorest 50% of the
population. This is not terribly surprising, on HN, but it is disappointing in
a discussion of how health care and the population at large interact.

There are so, so many broken assumptions that go into your response here, from
assuming that it's trivial to find out that a $300 plane trip would get you to
a cheaper provider, to the idea that "the next town over" is a reasonable
place to go when that's an hour's drive away and you've just been in a car
crash. It's just not worth trying to address every way in which you clearly
don't understand what it's like not to make 6 figures and live in a major
metropolitan area.

~~~
bhupy
> completely ignoring how they affect the poorest 50% of the population

You're absolutely right that there are some poor people that don't have the
ability to shop around. The solution to this isn't to centrally plan resource
allocation, it's to just give poor people money (UBI/NIT).

We do this already for food (food stamps). Food is also a life-or-death good,
one starves and dies if they don't have access to food.

There's definitely an argument to be made to increase food stamps and also
turn it into straight cash, but that's orthogonal.

~~~
danaris
And I completely agree. I'm 100% for a true UBI, but as long as that's not yet
politically feasible, I'm also for other solutions we can more likely
implement in the meantime (like Medicare For All).

------
DrAwdeOccarim
There is already stuff like this out there:
[https://www.biorxiv.org/content/10.1101/2020.02.01.929976v2....](https://www.biorxiv.org/content/10.1101/2020.02.01.929976v2.full.pdf)

Also, it appears as though convalescence therapy is working (i.e., treating
people with the plasma from recovered patients)
[https://www.straitstimes.com/asia/east-asia/china-seeks-
plas...](https://www.straitstimes.com/asia/east-asia/china-seeks-plasma-from-
recovered-patients-as-coronavirus-treatment) [https://news.yahoo.com/chinese-
doctors-using-plasma-therapy-...](https://news.yahoo.com/chinese-doctors-
using-plasma-therapy-161924314.html)

~~~
changoplatanero
Why cant they just extract the protein from the coronavirus?

~~~
DrAwdeOccarim
They can and are working on it/have already done it. The key then is to make
it in large quantities. One way to avoid needing to make the protein is to
deliver mRNAs for the heavy chain and light chain of the antibody. This would
be faster, but it is not a proven technology so it's unlikely to work anytime
soon (<1y) so convalescence treatment is much easier to do since blood
transfusions are super common and well established.

~~~
fredgrott
did they not have the same problem in doing the aids vaccine?

~~~
wbl
There isn't an HIV vaccine.

------
amelius
If you find a protein that blocks the virus, how difficult would it be to find
a drug delivery mechanism that is capable of reaching all the important cells?

~~~
pas
Isn't blood pretty good at this?

~~~
amelius
I'm not a biologist but I suppose that not every kind of protein enters any
kind of cell.

~~~
sp332
You need these proteins to interfere with viruses before they enter cells, so
that part is probably fine.

------
cbg0
Mirror: [http://archive.is/y67Ig](http://archive.is/y67Ig)

------
zedr
Fascinating... What are the odds against finding this particular type of
antagonist protein?

~~~
rolph
its already found, its just the finer details have to be investigated before
it becomes a legit treatment.

------
nednar
If there are people with expert knowledge here, can you explain how people
heal from such kind of virus (or in general) if there are no counter measures
external to the infected human?

I'm a little confused about how it works with virus vs bacteria.

~~~
rolph
in short terms, the immune system does it, but it has to learn what it is
first.

there are "tags" on the virus, these are antigens.

the immune system samples the antigens presents them to the "antibody
librarian" and the librarian publishes a bunch of antibodies that stick to the
virus antigen.

This can take some time to get to this state, during this time the virus is
replicating making you ill and doing damage.

when enough antibodies are being produced, new copies of the virus will be
tagged with the antibody and destroyed with haste.

here is a big read with all the real [complicated] terms:

[https://en.wikipedia.org/wiki/Immune_system](https://en.wikipedia.org/wiki/Immune_system)

this is basically the same process for virus, bacteria, and even some
nonliving materials.

------
hkt
HN hug of death?

~~~
russfink
Down at 6:52 ET

~~~
rckoepke
Intermittent. Reloading sometimes makes it work. Probably best not to reload
multiple times, that multiplies the hug of death effect. Just bookmark it and
come back later.

I feel silly, I've known about fold.it and fold@home for years now, but
somehow interpreted this title as a design for a binder, like a printable
cosmetic insert for a school binder.

------
mkchoi212
Noob question but what's the incentive behind people trying to solve puzzles
on this site?? Other than glory and fame of course :p

------
dmd
There's a Greg Egan short story "Zero For Conduct" that's about this kind of
site.

