Learning about protein crystallography just makes me appreciate the power of maths. I mean without it, I don't think any protein would be visible to us like now. I just thought how crazy it is to mathematically convert a screen of dots into a beautiful stunning 3D picture of a molecule. Amazing!
I live in amazing time. Each video about progressive science makes me positive about our future. Even if you are not scientist, just pay attention to new inventions, look at micro and macro cosmos and explore yourself.
This is incredible but it's almost easier to understand how this works today versus how they did it 60 years ago. I can't begin to imagine "solving" these structures without computers or even graphing calculators.
Sublime video. How is it that large molecules such as ribosomes can even be crystallised? They seem so huge and unwieldy that they would just tend to slop together into whatever arrangement that happened to fall.
I'm not a crystallographer but from what I have come to understand after watching lots of lectures on this technology is that even large molecules will tend to naturally crystallize quite easily as long as a few conditions can be met. One thing that greatly helps the process is that the solution of proteins is as homogenous as possible, but apparently that isn't absolutely necessary. The main catalyst for crystallization is due to additives and precipitants (hope I spelled that right). However, I don't know enough about chemistry to know why those chemicals have such a properties. Anyways, I think I got that info from this same channel, different video.
fullyawakened Getting the ribosome to crystallise was far from easy but it had to be done in order to solve the structure by this approach. It took years of work in many different labs around the world, first to crack bacterial ribosomes which are smaller. The one shown in the film is from yeast, also a single-celled organism but nevertheless a member of the 'eukaryotes', the branch of the tree of life that contains all multi celled organisms, such as ourselves.
Stephen Curry Thanks for the videos, and clarification. This stuff is so incredibly fascinating! These videos have spurred me to look up all kinds of documentaries on crystallography in the last week or so.
I always used to wonder, back in the days that space-flight meant STS & Salyut.... why they were constantly trying to grow protein crystals.... "what are these crystals FOR???" I often asked... Space journalists didn't help much... probably because they didn't actually know.... Got the answer in the end, but it's taken me a long long long time to get here.
I'm very interested in the subject matter, but the musical soundtrack was so distracting I could hardly stand to keep the video running. I kept looking around my desk saying "WHAT'S THAT CLACKING SOUND??"
It just makes me so curios that if this amount of awesomeness is happening at the molecular level, what is happening at the macro level that we just cannot see yet?
The background music is absolutely unbearable for anyone who has any sensitivity to sound. I couldn't watch the whole video, had to stop halfway, which is a pity since this documentary is fascinating.
Are those Xray diffraction plates filled with dark dots 3D? I've seen it always in books Illustrator a but I can't imagine how to use that to translate it to atomic arrangements
I understand how you would get the skelet of the protein from that diffraction pattern but I still don't get it how the computer can tell you what kind of atom is where, guess I would need a deeper explanation as a chemist.
The computer doesn't tell you this. In most cases we know it in advance because the amino acid sequence is known and chemists long ago worked out the atomic structure (and chemical composition) of those. The tricky ones to figure out are where you have metal ions bound to your protein; in these cases one can sometimes use X-ray fluorescence to identify the chemical species.
Stephen Curry Thanks for the answer, I thought computer does it all. Well that explains. Out of curiosity, is NMR spectroscopy not suitable enough for structure determination of these biological macromolecules in solution? I think I've attended a lecture about that previous semester, but I didn't pay too much attention, I just thought it must be very complicated. This sure looks more convenient.
Ace0077 NMR is a very useful technique for structure determination, especially if you can't grow crystals (which is a common problem). It gives you the 3D structure but not in quite so much detail as crystallography; plus, it's pretty hard to use NMR to solve the structures of large proteins. On the positive side, it can give information on protein dynamics that you don't get with crystallography. In practice, many structural biology labs use both approaches.
I think that for this technique to work, the X-ray beam needs to be collimated. The collimator is a tube with lots of microtubes in it. The majority of the X-ray photons gets absorbed. Only the straightest path photons make it out of the tube, therefore you lose a lot of brightness. In the case of gamma rays, first you need some methods of producing them. The second problem is that gamma rays are hard to collimate since they are hard to absorb. The collimator would have to be very long.
I could be wrong but I think the longer the accelerator, the more energy have the x rays produced, and that means they have a shorter wavelength than x rays produced in smaller facilites. So in a way they are increasingly going into the path of producing gamma rays, but its use would be more to determine the internal structure of atoms since for molecules x rays this powerful seem enough.
In this case it's largely because I (who co-wrote the script & presented) am a structural biologist. I'm sure there are some great stories to tell about the physics, chemistry, materials science etc. that goes on at Diamond but I'll leave it to other experts to take up the challenge.
Stephen Curry Now I feel sheepish for venting my (minor) frustrations online! Nonetheless, I thought it was well-written and presented. Disseminating science at this level to the broader community will always be a challenge, and this (along with the recent IUCr videos) are the best I've seen yet. Plus, it's interesting to see how the other half of the synchrotron lives :)
Hugh Simons No worries! You are right in any case that there should be more effort made to cover the physics and chemistry research that comes from synchrotrons (and other particle accelerators). As someone who originally trained in physics, I'm desperate to see Particle Fever: particlefever.com
How do X-rays help us uncover the molecular basis of life? Stephen Curry heads to the UK's most expensive scientific facility to find out Understanding Crystallography - Part 2: From Crystals to Diamond
@@lemueljohnurbano4448 I got it from ChatGPT Determining the specific atoms within a crystal structure based solely on diffraction patterns is a complex process that involves several steps and relies on fundamental principles of crystallography, chemistry, and physics. Here's a simplified explanation: 1. **Phase Problem Resolution:** One of the most critical challenges in X-ray crystallography is solving the phase problem. The diffraction pattern only provides information about the amplitude (intensity) of the scattered X-rays, not their phase (relative position). To determine the positions of atoms accurately, scientists must find a way to recover the phase information from the diffraction data. 2. **Fourier Transform:** The diffraction pattern is essentially a Fourier transform of the electron density distribution within the crystal. By applying mathematical techniques, such as Fourier analysis, scientists can convert the diffraction data into an electron density map. 3. **Model Building:** Based on the electron density map, scientists can begin to build a molecular model by placing atoms in the positions that best fit the observed electron density. This process involves trial and error, as well as refinement techniques to improve the fit between the model and the experimental data. 4. **Iterative Refinement:** The initial molecular model is refined iteratively through computational methods to optimize the agreement between the model and the experimental diffraction data. This refinement process adjusts the positions, orientations, and thermal parameters (e.g., atomic displacement parameters) of atoms to minimize discrepancies. 5. **Chemical Constraints:** Chemical knowledge and constraints also play a crucial role in determining the identity and positions of atoms within the crystal structure. For example, the known chemical composition of the sample and the expected bonding patterns based on the molecular formula guide the interpretation of the electron density map and the placement of atoms. 6. **Validation:** The final refined model is subjected to rigorous validation procedures to ensure its accuracy and reliability. This includes checking for geometric consistency, chemical plausibility, and agreement with independent experimental data. Overall, solving the phase problem and determining the specific atoms within a crystal structure based on diffraction patterns involve a combination of experimental data analysis, computational modeling, and chemical reasoning. It requires expertise in crystallography, mathematics, and chemistry to interpret the diffraction data accurately and derive meaningful structural information about the sample.
Ha ha - well spotted. It's true there are no hydrogen atoms shown in the molecular model that appears at about 6:21. Crystallographers often leave them out because they have many fewer electrons that the main constituents of proteins (C, N, O) and so contribute only weakly to X-ray scattering. They do appear and are included in models constructed using very high resolution data. For example, you can see them emerging as 'bumps' in the photo in this only blogpost which is of an electron density map of the highest resolution structure ever produced in my lab (about 1.45 Å) - occamstypewriter.org/scurry/2008/12/10/come_and_see/ In contrast, protein structures solved by NMR always include H atoms since these contribute very substantially to the data that are recorded in such experiments.
Thank you for the link, interesting data. Actually it was not the model that draw my attention but only the inaccurate statement itself. These details are just something one picks up studying Chemistry and I would be lying if I said I don't enjoy pointing out such inaccuracies ;)
minj4ever Well, I guess what my slip shows is that crystallographers tend to dismiss hydrogens because it is relatively rare for us to have to deal with them. Although the resolution of our data means they are usually invisible, we know they are there and can fairly easily determine their positions from a knowledge of chemistry. However, we're in the habit of not doing that calculation (unless it is necessary for understanding enzyme mechanisms or ligand binding). Personally, I prefer to look at protein structures without the H atoms shown because I think the models look too messy with them included! Of course, NMR spectroscopists tend to take the opposite view.
I'm sorry, but what a weak explanation. That x-ray crystallography is done by shooting x-rays at crystals (that was all that was explained about the subject in the video!) is evident just by the term "x-ray crystallography." And that background "music" was headache-inducingly terrible.
Wow CGI is truly considered proof in the science world nowadays. I also like how mathematics is used to create an image that nobody will ever be able to verify its actual existence. Science has truly become a religion, because so much is based on beLIEf.
What? Are you even serious? I'm not even sure why I'm bothering to reply, but: it's a visualization tool. The proof comes from a concrete, mathematical understanding of how light diffracts. The structure is solved from the diffraction pattern by, basically, a inverse Fourier transform of all the diffraction patterns captured. But, most importantly, where do you feel you've gotten the understanding that would be necessary to actually criticize crystallography's position as science? From this short video?
This mixes all 3 sciences together, studying proteins relevant in biology and using physics to identify structures at a chemical level. Dope.
It´s called Biophysics and you can study that.
My boi Curry shootin 3s and shootin beams🔥
lol!
If i saw this video 10 years ago I would have had a different major.
Resonating with that comment. Showing young people science videos like this might be a means of reinvigorating STEM fields.
Bryan, that is a very deep.
Learning about protein crystallography just makes me appreciate the power of maths. I mean without it, I don't think any protein would be visible to us like now. I just thought how crazy it is to mathematically convert a screen of dots into a beautiful stunning 3D picture of a molecule. Amazing!
I live in amazing time. Each video about progressive science makes me positive about our future.
Even if you are not scientist, just pay attention to new inventions, look at micro and macro cosmos and explore yourself.
Didn't know Steph Curry knew so much about science!
Wow, it is a very clear representation of how X-ray crystallography works, and it helped a lot! Many thanks!
do u have any idea how they analyse the image of x-ray to a structure!!
696 views ... these videos need to be seen by 696,000 - fantastic technology - wonderful science.
subscribing to this channel was a great idea.. this is very interesting
This is incredible but it's almost easier to understand how this works today versus how they did it 60 years ago. I can't begin to imagine "solving" these structures without computers or even graphing calculators.
Loved the quality of this video. It does a great job of describing how it works, to someone that has no knowledge of X-ray crystallography.
Sublime video.
How is it that large molecules such as ribosomes can even be crystallised?
They seem so huge and unwieldy that they would just tend to slop together into whatever arrangement that happened to fall.
I'm not a crystallographer but from what I have come to understand after watching lots of lectures on this technology is that even large molecules will tend to naturally crystallize quite easily as long as a few conditions can be met. One thing that greatly helps the process is that the solution of proteins is as homogenous as possible, but apparently that isn't absolutely necessary. The main catalyst for crystallization is due to additives and precipitants (hope I spelled that right). However, I don't know enough about chemistry to know why those chemicals have such a properties. Anyways, I think I got that info from this same channel, different video.
fullyawakened Getting the ribosome to crystallise was far from easy but it had to be done in order to solve the structure by this approach. It took years of work in many different labs around the world, first to crack bacterial ribosomes which are smaller. The one shown in the film is from yeast, also a single-celled organism but nevertheless a member of the 'eukaryotes', the branch of the tree of life that contains all multi celled organisms, such as ourselves.
Stephen Curry
Thanks for the videos, and clarification. This stuff is so incredibly fascinating! These videos have spurred me to look up all kinds of documentaries on crystallography in the last week or so.
fullyawakened Really nice to hear that! I'm sure you'll have seen the RI's Crystallography Collection: www.richannel.org/celebrating-crystallography
@@scurryww The link you provided is now hosting a Trojan according to Malwarebytes.
Thank you , I understand the concept very clearly
Hey, tell the host I said thanks for explaining how you work backwards from the diffraction pattern to the model like he said he was going to.
My head is exploding….Awesome video!
This video was beneficial to me. Thanks a lot!
Really informative and inspiring. Thank you dearly.
ingenius.. protein is actually smaller than the wavelength of light, yet how complex they look
Lan Fang nothing ingenious about it.
Love this series :D
I love it
I enjoyed watching this
Thats really AWESOME!!!
this is perfectly executed. thanks a lot :)
Excellent documentary.
Thank you for your wonderfully inspiring work!
Science for the win
Very cool.
eagerly waiting for the next one!!!
2015? Checks out.
Very helpful!
omg this is so amazing !
Wow 🖤
Super
This is SO rad.
Wow, just wow!!
Great video :) Thanks a lot
Great video!
Amazing video....!!!
that was so beautiful
thanks!
wow this was great !
CURIOSITY MAKES ME HERE:)
So cool😩😩😩
I always used to wonder, back in the days that space-flight meant STS & Salyut.... why they were constantly trying to grow protein crystals.... "what are these crystals FOR???" I often asked... Space journalists didn't help much... probably because they didn't actually know.... Got the answer in the end, but it's taken me a long long long time to get here.
Keren banget 😎 jadi pengen belajar di sana 😭🙏
What are the qualifications that this professionals have to work in this kind of thing?
I'm very interested in the subject matter, but the musical soundtrack was so distracting I could hardly stand to keep the video running. I kept looking around my desk saying "WHAT'S THAT CLACKING SOUND??"
Amazing - further proof that humans DO create the world around them!
It just makes me so curios that if this amount of awesomeness is happening at the molecular level, what is happening at the macro level that we just cannot see yet?
your mom
The background music is absolutely unbearable for anyone who has any sensitivity to sound. I couldn't watch the whole video, had to stop halfway, which is a pity since this documentary is fascinating.
4:55 'cinematic' one might say
Hi..
If you see a video of structure if a roughstone you can know if a Diamond? Id like send one.
Are those Xray diffraction plates filled with dark dots 3D? I've seen it always in books Illustrator a but I can't imagine how to use that to translate it to atomic arrangements
Haha Professor Stephen Curry, just like the NBA player. What a coincidence!
can you tell me which methods are available to. make crystal
Can't they develop a software to collect the diffraction patterns and through algorithms make them viewable? Rather than manually measure the "dots"?
Nevermind. They do seem to have a 3d software that reconstructs it
I understand how you would get the skelet of the protein from that diffraction pattern but I still don't get it how the computer can tell you what kind of atom is where, guess I would need a deeper explanation as a chemist.
The computer doesn't tell you this. In most cases we know it in advance because the amino acid sequence is known and chemists long ago worked out the atomic structure (and chemical composition) of those. The tricky ones to figure out are where you have metal ions bound to your protein; in these cases one can sometimes use X-ray fluorescence to identify the chemical species.
Stephen Curry
Thanks for the answer, I thought computer does it all. Well that explains. Out of curiosity, is NMR spectroscopy not suitable enough for structure determination of these biological macromolecules in solution? I think I've attended a lecture about that previous semester, but I didn't pay too much attention, I just thought it must be very complicated. This sure looks more convenient.
Ace0077 NMR is a very useful technique for structure determination, especially if you can't grow crystals (which is a common problem). It gives you the 3D structure but not in quite so much detail as crystallography; plus, it's pretty hard to use NMR to solve the structures of large proteins. On the positive side, it can give information on protein dynamics that you don't get with crystallography. In practice, many structural biology labs use both approaches.
Would it be possible to use Gamma-rays in place of X-rays, would that help and be possible?
I think that for this technique to work, the X-ray beam needs to be collimated. The collimator is a tube with lots of microtubes in it. The majority of the X-ray photons gets absorbed. Only the straightest path photons make it out of the tube, therefore you lose a lot of brightness.
In the case of gamma rays, first you need some methods of producing them. The second problem is that gamma rays are hard to collimate since they are hard to absorb. The collimator would have to be very long.
louis tournas
Thank you for the information, this will keep me busy for a while. :)
I could be wrong but I think the longer the accelerator, the more energy have the x rays produced, and that means they have a shorter wavelength than x rays produced in smaller facilites. So in a way they are increasingly going into the path of producing gamma rays, but its use would be more to determine the internal structure of atoms since for molecules x rays this powerful seem enough.
GCHQ or Apple HQ
Will AI make techniques like crystallography obsolete ?
I need these songs...
Outro: Ghosts - Grief and Sleep
FOLDING@HOME!!!
What's the song playing between 0:26 and 1:15?
It's 'Porto' by LASERS - you can find it here: freemusicarchive.org/music/lasers/
Thanks
Pr Grumpy cat
It's surprising what over-gifted people manage to do. Let's hope they will someday find a protein to help the other less-gifted ones to do the same.
Why the constant bias towards structural biology? What about the other 50% of the Diamond users (i.e. soft & condensed matter)?
In this case it's largely because I (who co-wrote the script & presented) am a structural biologist. I'm sure there are some great stories to tell about the physics, chemistry, materials science etc. that goes on at Diamond but I'll leave it to other experts to take up the challenge.
Stephen Curry Now I feel sheepish for venting my (minor) frustrations online! Nonetheless, I thought it was well-written and presented. Disseminating science at this level to the broader community will always be a challenge, and this (along with the recent IUCr videos) are the best I've seen yet. Plus, it's interesting to see how the other half of the synchrotron lives :)
Hugh Simons No worries! You are right in any case that there should be more effort made to cover the physics and chemistry research that comes from synchrotrons (and other particle accelerators). As someone who originally trained in physics, I'm desperate to see Particle Fever: particlefever.com
@@scurryww what you up to nowadays
How do X-rays help us uncover the molecular basis of life? Stephen Curry heads to the UK's most expensive scientific facility to find out Understanding Crystallography - Part 2: From Crystals to Diamond
TY for teaching us. And ty for sharing your knowledge.
***** and?
***** so I followed your instructions and now I like country music.
But how do they know the specific atoms based only on the diffraction patterns?
@@lemueljohnurbano4448 I got it from ChatGPT
Determining the specific atoms within a crystal structure based solely on diffraction patterns is a complex process that involves several steps and relies on fundamental principles of crystallography, chemistry, and physics. Here's a simplified explanation:
1. **Phase Problem Resolution:** One of the most critical challenges in X-ray crystallography is solving the phase problem. The diffraction pattern only provides information about the amplitude (intensity) of the scattered X-rays, not their phase (relative position). To determine the positions of atoms accurately, scientists must find a way to recover the phase information from the diffraction data.
2. **Fourier Transform:** The diffraction pattern is essentially a Fourier transform of the electron density distribution within the crystal. By applying mathematical techniques, such as Fourier analysis, scientists can convert the diffraction data into an electron density map.
3. **Model Building:** Based on the electron density map, scientists can begin to build a molecular model by placing atoms in the positions that best fit the observed electron density. This process involves trial and error, as well as refinement techniques to improve the fit between the model and the experimental data.
4. **Iterative Refinement:** The initial molecular model is refined iteratively through computational methods to optimize the agreement between the model and the experimental diffraction data. This refinement process adjusts the positions, orientations, and thermal parameters (e.g., atomic displacement parameters) of atoms to minimize discrepancies.
5. **Chemical Constraints:** Chemical knowledge and constraints also play a crucial role in determining the identity and positions of atoms within the crystal structure. For example, the known chemical composition of the sample and the expected bonding patterns based on the molecular formula guide the interpretation of the electron density map and the placement of atoms.
6. **Validation:** The final refined model is subjected to rigorous validation procedures to ensure its accuracy and reliability. This includes checking for geometric consistency, chemical plausibility, and agreement with independent experimental data.
Overall, solving the phase problem and determining the specific atoms within a crystal structure based on diffraction patterns involve a combination of experimental data analysis, computational modeling, and chemical reasoning. It requires expertise in crystallography, mathematics, and chemistry to interpret the diffraction data accurately and derive meaningful structural information about the sample.
what is this guy's accent?
Academic English :P
Every atom... except hydrogen
Ha ha - well spotted. It's true there are no hydrogen atoms shown in the molecular model that appears at about 6:21. Crystallographers often leave them out because they have many fewer electrons that the main constituents of proteins (C, N, O) and so contribute only weakly to X-ray scattering. They do appear and are included in models constructed using very high resolution data. For example, you can see them emerging as 'bumps' in the photo in this only blogpost which is of an electron density map of the highest resolution structure ever produced in my lab (about 1.45 Å) - occamstypewriter.org/scurry/2008/12/10/come_and_see/
In contrast, protein structures solved by NMR always include H atoms since these contribute very substantially to the data that are recorded in such experiments.
Thank you for the link, interesting data. Actually it was not the model that draw my attention but only the inaccurate statement itself. These details are just something one picks up studying Chemistry and I would be lying if I said I don't enjoy pointing out such inaccuracies ;)
minj4ever Well, I guess what my slip shows is that crystallographers tend to dismiss hydrogens because it is relatively rare for us to have to deal with them. Although the resolution of our data means they are usually invisible, we know they are there and can fairly easily determine their positions from a knowledge of chemistry. However, we're in the habit of not doing that calculation (unless it is necessary for understanding enzyme mechanisms or ligand binding). Personally, I prefer to look at protein structures without the H atoms shown because I think the models look too messy with them included! Of course, NMR spectroscopists tend to take the opposite view.
I'm sorry, but what a weak explanation. That x-ray crystallography is done by shooting x-rays at crystals (that was all that was explained about the subject in the video!) is evident just by the term "x-ray crystallography." And that background "music" was headache-inducingly terrible.
Wow CGI is truly considered proof in the science world nowadays. I also like how mathematics is used to create an image that nobody will ever be able to verify its actual existence. Science has truly become a religion, because so much is based on beLIEf.
What? Are you even serious? I'm not even sure why I'm bothering to reply, but: it's a visualization tool. The proof comes from a concrete, mathematical understanding of how light diffracts. The structure is solved from the diffraction pattern by, basically, a inverse Fourier transform of all the diffraction patterns captured.
But, most importantly, where do you feel you've gotten the understanding that would be necessary to actually criticize crystallography's position as science? From this short video?
@@BinaryHistory the Babble