Animating the Invisible: Molecular Movies and the Science They Reveal--Dr. Steve Corcelli, University of Notre Dame

Movies tell stories – whether it’s a gritty historical drama or a teen vampire romance – there are few better ways to absorb content than by watching events unfold on the silver screen (or in the comfort of your home). Similarly, Steve Corcelli's molecular movies welcome viewers into a new world with cutting-edge visualizations that capture the motion of molecules in real time, allowing researchers to observe chemical and biological processes at the atomic level. Dr. Corcelli spoke at one of the "Town Talks" presented by Telluride Science and the session was moderated by veteran broadcast journalists Judy Muller and George Lewis. 

Transcript

     Science Straight Up

Season 6, Episode 3

“Animating the Invisible: Molecular Movies and the Science They Reveal”

Dr. Steve Corcelli, University of Notre Dame

Moderators: Judy Muller and George Lewis

Comments: Mark Kozak, Telluride Science Executive Director and CEO

Recorded June 17, 2025 at the Telluride Mountain Village Conference Center

(theme)

JUDY: From Telluride Science, it’s Science Straight Up.

GEORGE: And this time around…

STEVE: I make movies for a living,   using computers to really visualize molecules in a unique way that feeds into a lot of other exciting efforts in the community.

JUDY: Dr Steve Corcelli is the chair of the Department of Chemistry and Biochemistry at Notre Dame, and Interim Dean of the College of Science. He and his team make movies showing how molecules move and interact with substances, not an easy task, since we’re dealing with tiny objects that can’t be seen with the human eye.

(sound: “Steamboat Willie”)

GEORGE: First, let’s talk a bit about animation, And go back almost a century to 1928, to the dawn of animated movie cartoons, with Walt Disney’s “Steamboat Willie.” It marked the debut of Mickey Mouse on the silver screen, and was hailed as groundbreaking for its mix of animated characters with synchronized sound. 

(sound---mickey whistles)

GEORGE: The artists at Disney had to draw almost eleven thousand discrete images, one for each frame of film that went into that 7-minute cartoon.  A lot of heavy lifting.

JUDY: Steve Corcelli’s people have to do much more complicated work to come up with THEIR images of molecules on the move. And we’ll hear about that and why it’s important.

(sound crowd)

GEORGE: The groups of scientists who gather each spring and summer, courtesy of Telluride Science, are hardy perennials, like the Columbine flowers that cling to the Colorado mountainsides. They’ll hold 58 workshops this year, exchanging ideas, arguing, questioning, learning.

JUDY: Once a week, the scientists share their cutting-edge ideas with the wider community in what Telluride Science calls “Town Talks.”  Steve Corcelli spoke at the Telluride Mountain Village Conference center.

STEVE: It is such a privilege to be with you here tonight.  I’m a computational chemist, so we do all our chemistry on computers.  I make movies for a living, using computers to really visualize molecules in a unique way that feeds into a lot of other exciting efforts in the community.

GEORGE:  Movies that show how molecules move and gather and get things done. Helping researchers develop new materials and, in the life sciences, perhaps help people live longer, healthier lives.

STEVE: Chemists and biologists and other scientists are, you know, trying really hard to understand this at a fundamental level, so that we can understand it so well that we can do things like, you know, understand diseases and how to cure those diseases and things like that.

JUDY: And being able to visualize it in motion aids in the understanding.

STEVE: Structure plus dynamics equals function, and that's why these movies are helpful, because we're going to understand, we're going to have structures, we're going to have that dynamics, and hopefully we're going to understand something about function,

GEORGE :  In one example, he shows a disease fighting T-cell coupling to a human cell that might be infected with a virus. The cells dance on the screen, then finally…

STEVE: Oh, it's getting close. And so now it's going to wiggle around until it really forms a nice, tight connection.

JUDY: Sounds like “R” rated material to me. 

GEORGE: A couple blobs of Jell-O. A mating ritual, maybe.

JUDY: Eeeuuw!

GEORGE:   Returning to science now. In another one of Dr Corcelli’s clips, a strand of DNA is pictured by some of that advanced imaging as the cancer drug daunomycin interacts with it. We see the drug pulling ever closer to the DNA, causing it to change shape, bending and stretching. 

STEVE: I could watch this one all day long.

GEORGE: Daunomycin has been around a while, and science knows it binds to DNA, but seeing how it does that  is revealing.

STEVE: Here's this molecule bound within the DNA. So if you remember DNA, it's got this double helix structure, okay, it's like a ladder, though you got rungs in the ladder.   This molecule can slide its way in between the rungs of the ladder. this thing's going to dance its way over. Sorry, no music. I'm not going to even try. But, you know, the DNA kind of bends. It does. The DNA itself does something weird to allow this thing, you see, it slid right in.

JUDY: The daunomycin worms its way into the DNA and stops it from reproducing, halting the cancerous growth. All of this happens in billionths of a second. The action has been stretched out to thirty seconds. Ultra super slo-mo.

STEVE: So yeah, so we actually just watch that drug molecule find its target and bind in.

GEORGE: The powerful microscopes picking up the images give the computers information on the trajectories of the individual molecules and then the computers assemble this into the movie clips researchers can study. Now, the question is, can this inspire new and improved drugs that will last longer with fewer side effects. Medical science might get some important insights from watching these movies.

STEVE: So this is, this is work that was performed by by a really talented student that I had the pleasure of working with, Erin Brossard. She now has a PhD, so she's Dr Erin Brossard. Remarkable, remarkable young woman.

JUDY:  Dr. Brossard (BROSS-urd) created many the animations over a five-year stretch, all while working on her doctorate and also, while being pregnant with twins. Let’s give a shout-out to female scientists. 

STEVE: Remarkable, uh, remarkable young woman.

GEORGE: Dr Corcelli says you ain’t seen nothin’ yet with artificial intelligence beginning to enter the picture.

STEVE: We may see a situation where scientists the process of discovering new materials and new drugs can get accelerated. And when I say accelerated, convert that in your head to cheaper. Gets cheaper. To make these new things, it costs billions and billions of dollars to bring a new pharmaceutical to market. This could, it's not going to cut it all the way down. This kind of stuff could, could have a real impact on making that more efficient, and that'd be great.

GEORGE: And then there’s the tantalizing prospect of what quantum computing can do in a few years from now.

STEVE: Quantum computers have the potential to be absolutely transformatively game changing. This is something I kind of expect we'll start to really see come along the next 10 to 20 years. it's gonna basically increase the computing power by potentially orders of magnitude. So now, again, I'm saying, you know, already we're starting to be able to do really cool things. Now imagine throwing another 10, 100 or 1000 or a million times more computing power, in essence. I just can’t imagine the things that will come from us having quantum computers so.. fundamental research is, is very near and dear to my heart. Because the thing about fundamental research, and why it's so important that we invest in it, is that you don't know what you don't know. And fundamental research is all about, like seeing what we can discover, and you can't always predict how it's gonna lead to that better living, to those new materials, to those you know, nobody went when it was like, Oh, we're gonna go to the moon. The goal was to go to the moon. The goal wasn't to make an iPhone or the internet, but all those things came anyway, and that's actually my one little one second pitch for fundamental science. So with that, Thank you so much. I appreciate it. Bye.(applause)

JUDY: Thank you so much.  I still have questions…A few questions before we open it up. Just your plug for fundamental research and basic research, I'm wondering if that's because funders want to know, well, what's it good for, and how do you sell that? Is that difficult?

STEVE: It's a completely reasonable question. And then people, you know, of course, want to see a tangible impact of the of the money that they're investing. That makes sense. I appreciate that. But the reality is that you know the way that things work in science, that this idea that you know research is is truly an act of discovery. I mean, you almost have to imagine you're kind of exploring terra incognita, that you're an old school explorer, that you really, truly don't know what's over the next mountain pass, and so you got to go there and look and and sometimes there's something really great, and sometimes it's not, and you don't always know the answer, but if you don't invest some amount, you will fall behind in terms of all the knowledge that you need to be more targeted towards a specific application that you might want to go after. 

GEORGE: I wanted to know more about how watching these short clips of animated molecules can advance things like medicine.

STEVE: That's actually that's an outstanding question. And so the way that that feeds in is, is that a lot of times that next cancer medicine is you need the insights about what is the shape, the structure, the interactions you need to know, all of this information to feed and that feeds into folks who are specialists at discovering new new drug molecules. So it feeds into what is a drug discovery ecosystem, if you will. So, you know, this is the thing about science these days, is becoming tremendously interdisciplinary. What people what that really means? Okay, you may hear that interdisciplinary. So what that really means is that you need lots of different people bringing different skill sets to bear on hard problems. So discovering new drugs is a hard problem, so you need, maybe folks like me, who are advancing the fundamental knowledge about how drug molecules interact and actually find their targets and work their way in and actually bind to their targets. But you also need people who discover what the targets are in the first place. We're actually talking about the Human Genome Project, how that's kind of, kind of, kind of, actually, that was a fundamental problem that that then fed into many applications that we're enjoying right now. So you need folks like that. And then you need synthetic chemists who make the drug molecules. You need biological chemists who test the drug molecules. You need clinicians who then bring it to the clinic and then test it and and, etc, etc, etc. So that is the that is the approach, is that you need all sorts of different types of scientists with different skills coming to bear on a single problem, and so I am just sort of one piece of a much, much, much larger ecosystem.

GEORGE Do you have a sense of wonder when you see these things for the first time?

STEVE: Absolutely, I when I say, I can sit around and watch these things for a while that that that is real because they they're somewhat mesmerizing, especially when you're also looking at them with a little bit of a trained eye, where you're kind of looking for specific things. And so it does. It's quite mesmerizing. And you know, the whole Seeing is believing that, that that's a big part of this. By being able to watch the chemistry, as it happens, is sometimes more insightful than any amount of reading about it, or or other ways of thinking about the material.

JUDY: You mentioned to us when we were chatting with you that there's an impending crisis, that bacteria are becoming resistant… 

STEVE:That's right.

JUDY: …to antibiotics. I think everybody knows about this. 

STEVE: Yeah 

JUDY: What does this work do to help scientists studying that problem and that problems here, really,

STEVE: No, that problem, that problem is definitely here. We hear about all the time. It's real. There are, there are pathogens out there, bacteria that are resistant almost to all of the known antibiotics. So it's a very, it's a very scary scenario to imagine that we could revert actually, you know, it wasn't that long ago, before the 1920s ‘30s, when, when you could die of a paper cut. Just Yep, people get a cut, and it would you'd be unlucky, it would get infected, and that infection could cause sepsis, and you could die. That is not something that we are really familiar with and comfortable with here in modern times, that we do not hear about being well, I got my friend got a paper cotton. So that's a very scary scenario. So how is it? Okay, so how is this, this specific research, again, fundamentals. We're trying to understand what we don't understand, and try to just understand how biology works. If you don't understand how biology works, it's very hard to hypothesize new, entirely novel approaches to developing antibiotic now, a lot of new classes of antibiotics, they simply work very differently than previous classes. Basically, scientists are attacking bacteria with new in a new direction, if you will, generating those hypotheses. This sort of fundamental work can be very useful for generating those hypotheses that then the other folks can follow through on and try to actually develop therapeutically active compounds. Okay, well, should we open it up? 

GEORGE: Yeah, let's open it up the audience now.

JUDY: There are always a number of scientists in the audience and we caution them to try to use layman’s language in their questions.

JAMES: I’m James Gaynor from Northwestern University and I will do my best to talk like a normal person.

GEORGE: James was so eager to ask his question that he earlier interrupted Steve Corcelli’s talk. We asked him to hold off a bit.

JAMES: So Steve…and I apologize also, I was operating in the usual modality that we have in these workshops, which is just to interrupt as soon as you're excited by something and just ask so…

GEORGE: We don’t use words like “modality.” (laughter)

JAMES: Steve, my question for you is, first off, these videos are amazing, and I think they give a lot of insight. But could you give us a sense for how you know that those are reflective of what happens, you know, yeah, in our bodies, that they're real?

JUDY: (NEW NARR) Great question. We know computers are getting pretty good at faking images these days, so how do Steve Corcelli and his associates make sure their images are the real thing? He says his team spends a lot of time validating those images, often through old-fashioned lab work.

STEVE: The way that we validate..we have lots of ways to validate the simulation, but generally speaking, we are seeking to connect to an experiment. So one of my experimental colleagues will make a measurement in their lab, and that we know is real, because they got the real stuff in their lab and they've made a measurement. And what we're often trying to do is to actually calculate what they measure in our simulations, and then compare it. And when it compares Well, we know that, we know we're doing a pretty good job and that and that we can maybe believe a lot of what else is going on in the movie. And when it performs poorly compared to experiment, we know we have problems, and we have to, you know, sort of think hard about about how to circumvent those problems. So, so, yeah, we spend an enormous amount of time as on those sorts of things and and these things are not perfect. Please don't walk away thinking that we do these simulations and they're absolutely perfect, but they're getting better and better, and they're definitely good enough that we often can, can get really tremendous insights.

GEORGE  it was a great review from from Northwestern University. How does the greater scientific community react to these pretty much the same? Are they blown away by it?

STEVE: I think, you know, people, scientists are kind of built to be skeptical. We're actually trained. We're like, formally trained skeptics, right? Like we basically are wired to be skeptical and to ask questions and to not just believe what another colleague is, but we do this in, what I can say, extremely fun and respectful way. We have structures in place. So you mentioned the meeting. We have these actually very spirited discussions, debates, even that tend to be fun and respectful and but we're critical of one another, asking these tough questions all the time.

JUDY: Another questioner wanted to know about what guides the molecules as they bind with one another. How do they know where to go?

STEVE: We are using some fancy methodology that helps. Basically, the methodology has information about the target. It's got information about what the final state is, and it uses that information to help guide it in a gentle way towards that target. So we do actually have something going on that helps a little bit to guide things. I'm not going to say anything else about that, because if I say even one more word about one more word about things are going to get very technical very quickly. But, but you're again, you're right on. You're right on the periphery of some real challenges in the field. Very cool.

JUDY: We got another one back here.

QUESTION FROM AUDIENCE: There are only so many hours in a day. There's only so many dollars in a budget. And so I wonder, if you might comment a little bit on, how do we prioritize, what directions of research we should devote resources to, or should we even try?

STEVE: Society has to decide, what are the important problems that that that we want solved? You know, society drives that to some extent. And, you know, maybe I'm, maybe I'm just way too optimistic for my own good, but I have this belief, and there's some evidence, that when scientists are engaged, the entire scientific community is engaged around massive challenges, and they are properly resourced. In other words, there's proper investment that the scientific community can solve just about any problem. And so we've seen that you want to go to the moon. You give the scientific community enough money, we'll go to the moon. You need to win a particular war, and that requires a weapon that maybe should not have made in the first place, but you did anyway. I'm talking about the Manhattan Project. Of course, you throw an absolutely massive amount of money, and then the scientists show up and the engineers show up with, you know, a nuclear bomb. So imagine just taking that and just deciding what is, what is that you care about? Is it solving Alzheimer's disease, cancer, climate change? So society has to decide that. But I'm of the belief that that once we have that will and the proper investment that that we have a community of scientists who will go after that challenge, and I have a lot of confidence that we can get there, even on the hardest problems, but it's about having that will. And that's where the science meets the politics and things are strange right now, and that's all say on that topic. Thank you so much.

(applause) 

GEORGE: Before we go, If you want to see some of the cool equipment Steve Corcelli and his colleagues are using, go to YouTube and search for “The University of Notre Dame, Department of Chemistry and Biochemistry.” They’ve got an interesting promotional video there.

JUDY: Finally, a little plug for Telluride Science and what it does.  Here’s Executive Director and CEO Mark Kozak.

MARK: If some of you don't know anything about Telluride science, what we do is, our purpose is, is to advance scientific knowledge and bring together global thought leaders to address societal and planetary challenges. And we do this by enabling leading scientists in their field to quickly propose a meeting,  bring together their peers and talk about new ideas and common research challenges in an environment that facilitates communication, collaboration, creativity, and so while we have most of our town talks here this summer, you know, Thanks to those sponsors, we are in full swing down at the Telluride Innovation Center with workshops every week, and we actually the building has allowed us to expand our workshops by 20% we are hosting 58 workshops this year, so that's pretty awesome for us. In terms of our impact on the advancement of science and technology. We are still in the final phase of raising the final 1.8 million. And if anyone is interested and can help us, we would love that. So we are accepting checks if you want to get involved.

JUDY: That’s it for this edition of Science Straight Up. Our thanks to our sponsors, Alpine Bank and the Telluride Mountain Village Owners’ Association.

GEORGE: In addition to Mark Kozak, the people who keep Telluride Science running are Cindy Fusting, Managing Director and CFO. Sara Friedberg, Lodging and Operations Manager and Annie Carlson, Director of Donor Relations.

JUDY: If YOU want to donate to the cause, go to Telluride Science-dot-ORG. That’s also where you can find our podcasts. And on your podcast apps like Spotify or Apple, look for “Science Straight up.”

GEORGE: A special thank you to our recording engineer, Colin Casanova. I’m George Lewis.

JUDY: And I’m Judy Muller, inviting you to join us next time right here on Science Straight Up.