Congrats to David Baker who just won the #nobelprize2024 "for computational protein design" with Demis Hassabis and John M. Jumper "for protein structure prediction!" We have several #iBiology talks by David Baker in addition to this one. Check them out on our website: www.ibiology.org/speakers/david-baker/
Congratulations! Anyone advancing theories and proving it for protein folding deserves plaudits. Just thinking about atomic attraction, seeking lowest level of energy till it's stable in its final form is truly amazing.
I remember your work so well early 2005 when I was finishing off my PhD in protein folding. Here we are in the days of youtube and myself playing with water clathrate structures and nanobubbles
Hi, Im currently working on a presentation for my studies about that exact theme. My Information’s are based on an article from the Nature magazine from the 15th September of 2016. In the article the scientists also use the Rosetta program to design proteins. In my understanding they first try to build the carbon backbone structure by finding the lowest energy state, and then they try to add the different sidechains for the tightest packing together with the lowest energy possible. Here is my question: Don’t alpha helices and ß sheets need specific amino acid residues to even exist, at least at some places? If so does the program calculate these specific amino acids into the primary structure to stabilize the secondary structure? Ps: The name of the article is: The Protein World
And I thought that the conformation that a protein adopts isn’t necessarily the global energy minimum, but rather a local energy minimum, where the protein would have to overcome a barrier to adopt the global energy minimum
how do you solve the problem with conformation distortion between bound and empty active centre. you probably need a certain deviation from minimal energy hole to allow flexibility and reactivity to substrates do you have a figure how much the predictive success when the in vivo folding matches to the in silico one?
@@rebeccakane8854 it is because interaction and ligand bindings cause different level of comformation changes and new interactions. so the new conformation most likely on a different energy level.
As a machine learning engineer without knowing anything about biology and protein, Can I be expert on it if I work hard? Im super ubber excited over this topic but a bit scared.
Best illustrations on drug efficacy, agonist, antagonist, protein design, and computational description of protein design ( Lineard potential, Hydrogen bonding model, and Monte Carlo Methods) and experimental methods particularly Nuclear magnetic resonance (NMR) and magnetic imaging. Thanks.
awesome, let's suppose sometime in the future we reach the level that we are capable of creating all essential elements in 3d all way down to electrons, program all laws of physics of the universe on a molecular level, start a virtual universe by launching the big bang in virtual reality and watch it as it evolves when all these elements randomly combine and interact with each other? will it evolve to produce intelligent 3D human beings capable of thinking and doing the same in their virtual reality? and.. are we the product of such achievement?
It is a theory that random processes randomly created the life(!) accidentally. Personally I do not support it, but saying that The God created the life does not help much. So we should try our best to learn the universe and life. The more we learn, the more we believe in God.
Fascinating. Designing, optimizing, implementing and integrating custom proteins. I had no idea this was possible. It's worth noting, however, that the discovery of the magnitude of intelligently-directed computer resources needed to make one protein is a strike against the possibility that undirected natural processes could have come up with any protein.
What's wrong, Ultimate? Wrong that there's too much complexity for proteins to have come about by chance? There are over 10^130 ways (permutations) to construct a small protein with 100 amino acids. But only a very small number of those will work for a particular function. How could any natural process select correctly against those odds?
@Ken Jackson I can suggest you one interesting book "The Selfish Gene" by Richard Dawkins. It talks quite a lot about evolution and other related stuff. I think what is false that you think that nature has to come up straight away with a protein out of nowhere, it actually does not work that way. Everything is build up step by step, if the step gives at least a minor advantage to the organism compared to the previous organisms, the organism will have a higher survival rate and more most likely more offspring. So, these minor changes add up and over millions of years new structures and proteins arise. Also, it is worth noting that nature usually uses previous proteins to build up new proteins (it does not create proteins from scratch), because lots of proteins share common domains and folds. I hope that helps!
Bootlee, what you have just recited is the dogma believed by the religion of Darwinism. The problem with this dogma is that new proteins CAN'T be built up step by step because they don't give any advantage at all until they're complete and correct. Proteins are totally dependent on their shape to do their job and the shape is totally dependent on the precise sequence of amino acids that comprise them. You can't get there a little at a time. Even if you start with an existing protein, there's no straightforward mutation path to get to another. The field of possible intermediate steps is too big to comprehend. As I mentioned, it's 10^130 for even a small protein. That's not a probability, it's the number of possible sequences. Remember the "correct" amino acids are just as likely to mutate as the "incorrect" ones. Any random random walk from functioning protein to functioning protein would take trillions of years during which there would be no functioning protein to fill the need.
I see what you mean, but nature reuses a lot of protein domains in various different proteins. I agree that protein dynamics, folding, de novo engineering does not answer all the questions yet, but do you have a better hypothesis to explain this phenomena?
Someone help me out here. If this scientists says he can design a protein by first designing the right DNA sequence to create it, but if some theologian agrees that sounds logical, and thus suggests that the first proteins (i.e., making up the first life) must have also required some great intelligence to design them (i.e., intelligent design), the man of God is considered an ignorant uneducated unscientific illiterate religious nutcase. How come he can teach intelligent design in the classroom, but such is forbidden to others?
Congrats to David Baker who just won the #nobelprize2024 "for computational protein design" with Demis Hassabis and John M. Jumper "for protein structure prediction!" We have several #iBiology talks by David Baker in addition to this one. Check them out on our website: www.ibiology.org/speakers/david-baker/
David Baker won the Nobel Prize today!
This guy is an amazing individual and I hope he goes far in life.
instaBlaster.
@@saulbraydon5010sounds like my ex wife!
He got the Nobel today
@@themrvims I came here just to comment this
This comment aged quite well
Congratulations! Anyone advancing theories and proving it for protein folding deserves plaudits. Just thinking about atomic attraction, seeking lowest level of energy till it's stable in its final form is truly amazing.
And here we're in the Alphafold/Rosettafold era. Kudos to these guys who worked hard to achieve the solutions.
David Baker was one of them. He's the best in the world at protein design and folding.
I'm about to get my bachelors degree in Biochem. Eng. down here in Mexico. People like Mr. Baker inspire me. Great content
I remember your work so well early 2005 when I was finishing off my PhD in protein folding. Here we are in the days of youtube and myself playing with water clathrate structures and nanobubbles
I literally cried during the protein folding sequence, such beautiful and inspiring work
He is one of my docs'. Believe me! He has/is!
Congratulations 🎉for winning the Noble Prize 🏆
Interesting info and challenge. Nice graphics and good explanations. Thanks. Do you ever think (or worry) about making prions?
Congratulations 🎉Mr David Baker for Winning the Noble prize 🥇 2024
So unique and motivated work. Thanks for sharing.
Hi,
Im currently working on a presentation for my studies about that exact theme. My Information’s are based on an article from the Nature magazine from the 15th September of 2016. In the article the scientists also use the Rosetta program to design proteins. In my understanding they first try to build the carbon backbone structure by finding the lowest energy state, and then they try to add the different sidechains for the tightest packing together with the lowest energy possible. Here is my question: Don’t alpha helices and ß sheets need specific amino acid residues to even exist, at least at some places? If so does the program calculate these specific amino acids into the primary structure to stabilize the secondary structure?
Ps: The name of the article is: The Protein World
I too have the same question have u got the answer
Answer?
And I thought that the conformation that a protein adopts isn’t necessarily the global energy minimum, but rather a local energy minimum, where the protein would have to overcome a barrier to adopt the global energy minimum
Very well paced and interesting
this man is a super super smart guy.
loved it, thank you so much for uploading this.
2024 Nobel prize in chemistry 🎉🎉🎉🎉🎉
how do you solve the problem with conformation distortion between bound and empty active centre. you probably need a certain deviation from minimal energy hole to allow flexibility and reactivity to substrates
do you have a figure how much the predictive success when the in vivo folding matches to the in silico one?
I am confused why would you need a deviation from minimal in order to allow for flexibility and reactivity to substrates?
@@rebeccakane8854 it is because interaction and ligand bindings cause different level of comformation changes and new interactions. so the new conformation most likely on a different energy level.
As a machine learning engineer without knowing anything about biology and protein, Can I be expert on it if I work hard? Im super ubber excited over this topic but a bit scared.
Best illustrations on drug efficacy, agonist, antagonist, protein design, and computational description of protein design ( Lineard potential, Hydrogen bonding model, and Monte Carlo Methods) and experimental methods particularly Nuclear magnetic resonance (NMR) and magnetic imaging. Thanks.
Great, will living things use these??? One wonders if there is an information differential between made in lab and made in cell??? Thanks
Protein structure is complex. (2:22)
10:30 Design principles.
How to send the design to the new protein?
Just awesome! I would like to join your team
This video keeps me PhD movitated
don't be demotivated
I thought each amino acid could take 10 different conformations.
Thank you for this great video.
awesome, let's suppose sometime in the future we reach the level that we are capable of creating all essential elements in 3d all way down to electrons, program all laws of physics of the universe on a molecular level, start a virtual universe by launching the big bang in virtual reality and watch it as it evolves when all these elements randomly combine and interact with each other?
will it evolve to produce intelligent 3D human beings capable of thinking and doing the same in their virtual reality? and..
are we the product of such achievement?
It is a theory that random processes randomly created the life(!) accidentally. Personally I do not support it, but saying that The God created the life does not help much. So we should try our best to learn the universe and life. The more we learn, the more we believe in God.
Truly Amazing, thank you!
WOW!!!!
Amazing!
18:50 "you see that the crystal structure is nearly identical to the design model"
doesn't look like it to me
...aah...
AYE YO YALE BIO 101 TURN UP
catch me watching this 1 am the night before section lmaooo
*Oh dear god*
Fascinating. Designing, optimizing, implementing and integrating custom proteins. I had no idea this was possible.
It's worth noting, however, that the discovery of the magnitude of intelligently-directed computer resources needed to make one protein is a strike against the possibility that undirected natural processes could have come up with any protein.
Wrong. False.
What's wrong, Ultimate? Wrong that there's too much complexity for proteins to have come about by chance? There are over 10^130 ways (permutations) to construct a small protein with 100 amino acids. But only a very small number of those will work for a particular function. How could any natural process select correctly against those odds?
@Ken Jackson I can suggest you one interesting book "The Selfish Gene" by Richard Dawkins. It talks quite a lot about evolution and other related stuff. I think what is false that you think that nature has to come up straight away with a protein out of nowhere, it actually does not work that way. Everything is build up step by step, if the step gives at least a minor advantage to the organism compared to the previous organisms, the organism will have a higher survival rate and more most likely more offspring. So, these minor changes add up and over millions of years new structures and proteins arise. Also, it is worth noting that nature usually uses previous proteins to build up new proteins (it does not create proteins from scratch), because lots of proteins share common domains and folds. I hope that helps!
Bootlee, what you have just recited is the dogma believed by the religion of Darwinism. The problem with this dogma is that new proteins CAN'T be built up step by step because they don't give any advantage at all until they're complete and correct.
Proteins are totally dependent on their shape to do their job and the shape is totally dependent on the precise sequence of amino acids that comprise them. You can't get there a little at a time.
Even if you start with an existing protein, there's no straightforward mutation path to get to another. The field of possible intermediate steps is too big to comprehend. As I mentioned, it's 10^130 for even a small protein. That's not a probability, it's the number of possible sequences. Remember the "correct" amino acids are just as likely to mutate as the "incorrect" ones. Any random random walk from functioning protein to functioning protein would take trillions of years during which there would be no functioning protein to fill the need.
I see what you mean, but nature reuses a lot of protein domains in various different proteins. I agree that protein dynamics, folding, de novo engineering does not answer all the questions yet, but do you have a better hypothesis to explain this phenomena?
Someone help me out here.
If this scientists says he can design a protein by first designing the right DNA sequence to create it, but if some theologian agrees that sounds logical, and thus suggests that the first proteins (i.e., making up the first life) must have also required some great intelligence to design them (i.e., intelligent design), the man of God is considered an ignorant uneducated unscientific illiterate religious nutcase.
How come he can teach intelligent design in the classroom, but such is forbidden to others?
and he's not even a real baker.. wow...
grrr