"Good Vibrations: Water, Proteins and the Molecular Motions that Make Life Possible"

Water is far more than a refreshing drink — its unique molecular properties make life possible. By forming a dynamic network of weak chemical bonds, water acts as both a selective solvent and a kind of molecular lubricant, driving the assembly of cells and keeping the tiny protein machines inside them flexible and in constant motion. Understanding the role water plays in the generation of these vibrations is one of the great frontiers of modern science, with real-world implications for greener industrial chemistry and smarter, safer drug design.

Transcript

Science Straight Up, Season 7, Episode 2

Good Vibrations: Water Makes Them Possible

Dr. Matthias Heyden—Arizona State University Research Scientist

Moderators: George Lewis and Judy Muller

(Theme music full then under)

GEORGE: From Telluride Science, this is Science Straight Up. I’m George Lewis

JUDY: And I’m Judy Muller. On this edition, we’re going to talk about the good vibrations in the molecules that make up our bodies and how they share those vibes with the water molecules that surround them. Science is just beginning to understand how important this is.

MATTHIAS: (45:23) And it turned out what we were seeing were vibrations in the water around the proteins, and that was a whole new perspective that we didn't have before, and that was, that was amazing.

GEORGE: Dr. Matthias Heyden (HY-den) with Arizona State University is a molecular biologist by training and he started out in traditional laboratories. He spoke at one of the “Town Talks” sponsored by Telluride Science.

MATTHIAS: (33:28) My degree is in biochemistry, so I learned how to basically pipette tiny amounts of liquids into other tiny amounts of liquids, and basically see what happens.

JUDY: But these days, his experimenting is done by computer simulations and modeling.

MATTHIAS: (40:54) We are still kind of in the beginning of being able to control the dynamics of proteins, first of all understanding them, simulating them, and then controlling them.

(SOUND—mosh pit party)

GEORGE: His computer simulations show kind-of a mosh pit of molecules 

(SOUND—more mosh pit)

GEORGE: OK, so we’ve added some noise here.

A mosh pit of molecules   looking like vibrating clumps of ping-pong balls, wiggling, jiggling, dancing around. And, here’s the interesting part, also interacting with molecules of water. 

MATTHIAS: (04:10) Water is, of course, made out of hydrogen. Hydrogen is the simplest element, it's just one proton, one electron, and therefore it's also the most common element in the entire universe, and it's followed closely by oxygen, which is a little bit more complex, but it's a third most common element of the universe. If you combine these two, then you have pretty much for most, or one of the most abundant molecules in the entire universe.

GEORGE: But, when you study water with an array of new tools, it turns out there’s more to the stuff than just H2O.

(SOUND—San Miguel River)

JUDY: That’s the sound of the San Miguel River. It flows right behind the Telluride Science and Innovation Center where Matthias Heyden (HY-den) and hundreds of other scientists have been holding their cutting-edge workshops.

MATTHIAS: (01:44) I've been coming to Telluride since 2012 for these meetings. They really have had a very, very big impact on my career. (02:18) So, I want to talk today about water. You all know what water is. It's nothing new to you, obviously. We drink it a lot. Most of you kind of consist primarily out of water, so it's not a particularly new substance to you. But I hope I can show you that there's another side to water that, if you're not a chemist, you may not have thought about it before.

JUDY:  Going back to those wiggling, jiggling molecules, Matthias Heyden and his colleagues are looking at how water transmits molecular vibrations from one place to another.

GEORGE: Some researchers believe that selected proteins and enzymes may have evolved to vibrate in specific ways that increase their powers…that those vibrations—carried by water--may be more crucial to life than previously known. While Mattias Heyden was working on his doctorate with an advisor named Martina Havenith they began to look at vibrating proteins using laser beams.

MATTHIAS: (45:15) In the beginning of my PhD, when I started working with Martina, based out just started using a new laser to actually study vibrations and proteins, and it turned out what we were seeing were vibrations in the water around the proteins, and that was a whole new perspective that we didn't have before, and that was, that was amazing, and I started doing simulations a lot to understand what's going on, so that was actually very nice, because experiments and simulations were going hand in hand

JUDY: Lately, he’s been looking at an enzyme called beta-lactamase.

MATTHIAS: Beta-lactamase is basically a protein that helps bacteria to get rid of antibiotics, which is not good. It makes basically bacteria, which are resistant to antibiotics.  

JUDY: Beta-lactamase sabotages antibiotics like penicillin and others, rendering them ineffective. Understanding the evolution of this protein could help drug makers formulate new antibiotics that are fortified against it.

MATTHIAS: (40:02) We can basically build statistical models that go backwards in time and predict what did this protein originally actually look, look like, and we can make this protein and basically study it.

GEORGE:  And while we’re discussing drugs, let’s spend a minute talking about cancer chemotherapy. Here’s Julia Wilde of D News.

(DISCOVERY CHANNEL) “Technically, chemotherapy is a poison but it’s a poison that ultimately saves lives. The original chemotherapy drug was a derivative of mustard gas. It’s a pretty barbaric treatment.”

GEORGE:  Anyone who’s had chemo or who’s seen a loved one undergo it knows that the treatment sessions can be a long ordeal…as the drugs slowly drip into the patient’s veins.  Many chemotherapy drugs are not easily absorbed into the human body.  And they have all sorts of debilitating side effects, hair loss, nausea, fatigue, on and on.

JUDY: But now, imagine a whole new generation of cancer drugs that could use those molecular vibrations to better harmonize with the body’s chemistry, directly targeting cancer cells without all the side effects. And getting absorbed much more rapidly.  So, how close are we to that?

MATTHIAS: (40:25) Not very. We're getting there. So, out of all the drugs of the market, last time I checked for literature, basically 99.9% of all drugs on the market were not using that mechanism. There were the traditional ones that are described, and we had maybe 10 drugs on the market that used this, we call it an allosteric mechanism, and almost, not almost all of them were discovered by accident, so none of them were basically created by design.

GEORGE: An allosteric site on a protein is a place that’s distinct from the protein’s main site, but a spot where that protein can be regulated, its functions either enhanced or inhibited. Switch on the good proteins, switch off the bad ones.

MATTHIAS: (40:54) We are still kind of in the beginning of being able to control the dynamics of proteins, first of all understanding them, simulating them, and then controlling them. This is still more or less in the beginning, getting better and better every, I would say, month, but we still have a way to go.

JUDY: It isn’t just drugs we’re talking about. Dr. Heyden (HI-den) foresees a world in which designer proteins may lead to environmentally-friendly industrial processes that don’t generate a lot of heat and pollution.

MATTHIAS: (43:11) That's our idea to design new proteins that actually don't exist in the real world, but are able to catalyze, meaning speeding up chemical corrections, not in high-pressure reactors and big, big kind of factories, but basically just in a little container of water at room temperature that will change chemistry completely. And again, we are getting where these things actually exist, but getting making these proteins at scale, making them stable enough so that you can reuse them over and over, there's still a lot of work that has to be done.

(48:40) I'm still at the kind of basic research. I'm trying to figure out very basic things for other people that work closer to the applications, and it's not - it's never going to be a single person that basically solves the whole problem. It's many, many people that basically look at individual pieces, and everything we do is often so complicated that it becomes at some point even hard to talk to each other, because it's hard to understand, and this is again something that AI actually helps, because AI can learn the different, let's say, languages that different people speak and translate between these two.

GEORGE: Judy wondered how Dr. Heyden, (HI-den) as a young man growing up in Germany, developed his enthusiasm for science.

JUDY: (from talk 42:36) We love to hear about why scientists get into a particular field. Do you remember something that excited you about water? That I mean, what led you to this research?

MATTHIAS: Yeah, it was interesting. It's not something I ever planned. My grandfather was a chemist, but he passed away when I was six, so I never was really able to talk to him about it. And my parents don't have high school degrees, so they never really graduated, so I started studying chemistry, which was after high school. Basically, the thing that seemed reasonable to do chemistry alone seemed a little bit boring, so I added bio to it without really knowing what I was doing. And there was one particular lecture in biochemistry where they basically talked about proteins, that proteins are long chains of amino acids, and they fold in a particular structure, and back then our professor basically told us this is, we know they do that, we know they do it in a very particular way, but there's no way to predict it, and that's something I could not accept. So I started playing with mathematical models, which are complete nonsense, but I made them basically up until I've later learned that these things actually exist, and this led to computer simulations, so that was one particular important part. And then later, I discovered quantum mechanics, which is something biochemists are usually spared of but it was actually a lecture that Martina Havenith gave and I wanted to know more about that. It was so weird, so different, things that I had never seen…mathematical concepts I’d never seen before. So I joined her research group back then, do laser spectroscopy, shoot lasers at things, then learned later how to describe that mathematically, and that was just a fantastic experience. Suddenly, you’re just a student, you go to a lecture, you listen to stuff, and suddenly you’re in a research group and you have lasers which are super-expensive and you play around with them and you try not to break them

JUDY: It turns out Dr. Heyden is a bit of a sci-fi fan. He mentioned the popular movie ‘Project Hail Mary,’ where Ryan Gosling plays a scientist astronaut trying to save the planet.

RYAN GOSLING FROM TRAILER: “I understand you think I’m the right person for this mission. I understand the stakes.”

 JUDY: To help him carry out that mission, he forms a buddy relationship with an extra-terrestrial who happens to be a mineral-based life form.

GOSLING: “I’m gonna call you Rocky. We’re here for the same reason.”

MATTHIAS: (2:05) How many of you have seen the Project Hail Mary movie? Fantastic movie, the book. book is even better. The audiobook is even better. Every speaker is fantastic, but in that movie, there's like a central plot line. There's a scientist, which is kind of the protagonist of that movie, who claims that life could exist without water. And in that movie, it's very controversial. It's basically outcasts from the scientific community and reality, it's actually not like that. Water is very important. Water is very important for life as we know it, but there may be other forms of life.

GEORGE FROM TALK: So what do you think the probability is of non-water based life somewhere in the universe?

MATTHIAS:  That is a tough question. One of the forms of life, life usually requires complexity. Life requires the ability to copy information, and there are certain kind of actually just learned that from Rick, because he was here last week, and he talked about it. Complexity is something that they can quantify. We have certain kind of mathematical tools to do that, and you actually find complexity in living systems, but you also find them somewhere else, for example, in minerals, not sure if some of you have seen, like fancy crystals and things that grow in particular ways. There are minerals that actually have a complexity which is on par with life. It doesn't make them living things, but they have a necessary kind of molecule complexity, the complexity of how to arrange molecules in a similar way like what we see in results, and sometimes we can even mistake these structures for life, like if we look, if we are going to Mars at some point and are looking for signs of life, sometimes mineral composites actually look pretty much like remnants of actual life, and they're not so easy to distinguish sometimes. 

GEORGE: Then, there was a question about good old salt—sodium chloride.

AUDIENCE MEMBER: So, after this, I'm going to go have a salty dinner. And I noticed that the models that you showed us didn't include ions in the water. When you have ions in the water, like sodium, does that tip the scales of the tug of war between the direct and water-mediated interactions that you see?

MATTHIAS: Once you add ions to the mix, they do something weird. You add more charges to the system, but that actually makes interactions between opposite charges overall weaker, because now you kind of introduce all these kind of detractors that have also positive and negative charges, so salt completely modulates or changes the interactions between molecules in water, and also the interactions between molecules from smaller molecules themselves.

GEORGE: For those of us who did not ace chemistry 101 can you translate that question and answer into plain English?

MATTHIAS: I can try, so salt table salt, um, it's a kind of mix of two different types of ions, sodium and chloride. One of them has a positive charge, one of them is a negative charge. That's why they arrange themselves into these crystals that you see in your, in your salt applier. I don't know how to translate that. Um, but they make these nice crystals, however, these positive and negative balls, they can also interact very well with water. These hydrogen bonds that I mentioned, they can form that with the negative chloride ions. They have similar strong interactions with the positive cations. So, even though these crystals, these salt crystals are super stable, once you bring them into water may dissolve because the interactions that these ions can make the water are even stronger, so that's that's that's one important important piece, and once these ions are there, the interactions between water molecules are totally different, and these water media interactions are changing as well.

AUDIENCE MEMBER: Who funds your research?

MATTHIAS: Currently? It's the National Institutes of Health and the National Science Foundation.

JUDY: And how is that going?

MATTHIAS: So far, actually pretty good. I have no complaints. I didn't suffer any cuts or anything like this, so that's something. When I came to the US, I had to learn how to define proposals and write them a way that people understand me. Our German system is a little bit different here. You have to really kind of nail the point very early on in what you write, and it took me a few years to learn that, but since then it's been doing quite well, and I'm very generous, very grateful for the support.

(SNEAK THEME UNDER)

GEORGE: And here’s hoping that support for Dr Heyden’s fascinating and important research continues.  That’s about all the time we have for this edition of Science Straight up.

JUDY: We’d like to thank our sponsors, Alpine Bank and the Telluride Mountain Village Owners’ Association.

GEORGE: Mark Kozak is the Executive Director and CEO of Telluride Science and Cindy Fusting is the managing director and CFO.

JUDY: Sarah Friedberg is Lodging and Operations Manager and Annie Carlson is in charge of donor relations.

GEORGE: If you’d like to donate to the cause, go to telluridescience-dot-O-R-G. You can also find our postcasts there or search for “Science Straight Up” on your podcast apps.  This is probably too much information, since you’re already listening to our podcast.

JUDY: If you think George is being too redundant or if you have other comments or questions for us, you can email us. That’s sciencestraightup at telluridescience-dot-o-r-g. This podcast was recorded by Colin Casanova. I’m Judy Muller.

GEORGE: And I’m George Lewis, inviting you to join us next time on Science Straight Up.

THEME UP AND UNDER:

GEORGE: And we’ll give you a little moment of Zen at the end…the San Miguel River.

RIVER SOUNDS UP FOR A FEW SECONDS AND FADE OUT