 The protein design community here is actually growing pretty fast now and we are at the point that we can design protein structures. The challenge is now people are facing is to design the proteins with the embedded functions like if you want to design enzyme to do the enzymatic thing like to cut peptide bond or to stage peptide together if you want to design that that's hard that's real hard because protein function when protein function it's a dynamic process it's not like a solid rock right it's not just sit there and do nothing it actually moves around and do things but how you design this dynamic thing it's really hard to be able to develop that kind of therapeutics you can't get away from making the mirror image protein molecules you want to make that how do you make that you need new technologies that's what we're doing for us we will collaborate with the people like life science school of science at wrestling university and other people's too other people too and we will see like which molecule which target is the most relevant like therapeutic target or it's the most like medically unmet like needs for the patients we focus we identify that first and then we use all the approaches we have no someone's opinion may contradict yours where's my friend allen it's all about your perspective who are we and what is the nature of this reality five four three two what's up everyone welcome to simulation i'm your host alan sakein we are on site at the beautiful west lake university in hangzhou china we are now going to be talking about protein technologies we have dr bobo dong joining us on the show hi bobo hi thank you so much for coming on the show sure really appreciate it i'm so excited to have you for those who don't know bobo's background he's an assistant professor and principal investigator at west lake university focused on protein synthesis and engineering and you can find his links in the bio below okay but let's start things off by asking one of our favorite questions what are your thoughts on the direction of our world yeah i mean the world is moving forward for sure and then i think i think the meaning of the world is just like it needs to provide opportunity for every single human being to explore the unknown nature of like science maybe territory to the unknown world but then to do that you have to have a like healthy lifespan to to to enable yourself to do that like for example myself if i got an injury i can't go up and do things right so we do have the maybe the health system or maybe the technologies to enable the society can ensure or provide the like stage for everybody to do that and then for us like working in the like protein science or like health biotechnologies or pharmacologies like and other things we are the people to do that like to to come up with strategies or like different ways like to repair people to treat people when they really don't have like the healthy body so i think i'll be dedicated in my career to like to this goal like to people who wants to explore the world and then to make sure like these people are like in the healthy states and then they can do that i think i think that will be my angle actually so how to do that how to do that of course there are different ways like we take different approaches like you can either develop like technologies like like surgery and they do surgeries right they they they fix people and then people like me like we develop like protein therapeutics which is like the leading like technology in the 21st century like to to treat patients like to fight cancer to like and other diseases so i'll be working on that too yeah there's two thoughts there one of them is increasing the basic needs for everyone around the world to be able to actualize their unique gift and potential i love that and then the other one is the the ability to be able to make targeted therapeutics for tackling some of the biggest complex diseases that we have to prevent pathologies from developing in the first place to stay healthy longer so we can be more creative pass more time with our families find more meaning all this kind of cool stuff yeah how about your journey who were you as a kid growing up how did you get interested in science and proteins yeah i think for me myself i think it's all it's always about like curiosity like like growing up i think i'm pretty curious about like different things like i mean i go out in the field i look at things like i wonder why p what what things why burst fly like what something you can see the color like the fairfly right how does it work i mean i'm always curious about these things like i mean i go to a school of course i love science and then i do pretty good on science too and especially i was attracted to chemistry so that's what i love the most and like pretty much since since like undergrad i took the chemistry at my major and then in undergrad i think i developed interest you know like especially in peptides and proteins because i mean these are the things that made up the human body like made up like pretty much the living living world so i was really into these things and trying to figure out how these things work and then maybe if we can if people can do something with that like some interest things maybe at that time i i wasn't really sure like well i can well i can contribute to this like proteins are so big like if you can how do you like make therapeutics using protein molecules how do you like even manipulate things like maybe maybe you like create life like doesn't exist in the world i mean back then i wasn't sure right but then gradually i developed the interest and then i tried to study more and more like after my undergrad i felt i really love protein so i want to make protein molecules just like organic chemistry make like small molecules right so i went to chicago and joined the steve kent's lab okay right before we get to chicago yeah okay so i love this young bobo that i'm envisioning right now that's constantly going and finding the why is it birds fly why is it that this is this way that is that way how do i you know ask these questions so you can understand the reality that you were in and then it was this this understanding that you know if maybe if you can understand proteins which proteins make up is it all of life's functioning most of it most of it's functioning right that's so interesting and so we'll be breaking that down and so then you that was kind of a big like ultimate why is like you know why is that and then how can i be an engineer in that space of proteins okay i like that and then um now uh yeah so then okay after doing um nanjing university was where you did your bachelors then you decided to move this is a big move to the university of chicago so i want you to explain to us um you were there until you did your phd in chemistry there um and we'll talk about what you were doing but first let's talk about how did you decide to move to the united states and also what was it like when you first arrived yeah i think the nature of myself is just like i like to explore things like i mean i could i'd like to go out nature and explore like things too like for the science aspect it's the same like i was i mean i was studying china but like it's it's not too much advanced back then i think the leading the leading the leading force is still in the us so i i wanted to go to the us and see what's up there and just see like if i find like things getting more interesting or not so i decided to go to the us and then i also face my personal interest because i like to explore different things i want to see the world right and see like what are the people doing what are the cultures like so i went to the us and then i joined the lab the lab was actually really good because the the p i was like was really like close to people so and then like it's the people also don't like really tell people what to do so you adjust the like it's just like you have a lab and then you explore yourself to do to see what what what you are interested in then decide what to do and when i first got it got to the us so the lab was actually really good apart from the lab like in the in the in my personal life it it was a little bit difficult i will see because my english was not this good back then i can't really quite talk to people like all the time so that took me some time so i tried to i mean i just i like to go out and talk to people and then have fun with people so that's how i tried to like merge into the society and merge like just making your friends and then and then grow like gradually see like gradually like developing like like relationships with the different people and then eventually with the society and i feel like i'm i'm actually pretty comfortable in there yeah because like the the us i think in the spirit of many us like in the spirit of the of the nation like they actually go explore the world i think that's actually rooted in us i like that too so i'm like the same so i like that and i i mean i like the life personal life i like lab too so it's actually a perfect fit for me yes yes and then when you're there what does this mean protein ion channel like ligands oh right yeah so that's uh that's a mouthful yeah there are not many things in there so first i can actually give you some introduction let's do the introduction for us yeah yeah or some animals yeah like we're all familiar with like animals like spiders scorpions right and these are like i mean we see them all the time and then we know that dangerous because if you got bitten or if you got stung by these things you'll get hurt some people get killed by those things but what really happens for these things is that these animals they make some like pretty small protein molecules and these molecules they can actually interact with the like ion channels which are membrane proteins by yourself so this protein when the animal bites you or stuns you they inject these like little like missiles into your body and these small proteins go out and find these like ion channels and then they either block the ion channels then you cannot feel anything so you become numb some of them become really like really nasty like they stop they block the ion channel they modulate the function eventually like people might lose the lose the hand or lose the legs so those are actually like really interesting molecules they could they could be really dangerous but because the these molecules they function against these like ion channels or like other cell membrane receptors so they were actually harassed by like scientists to study these like receptors or ion channels because traditionally you don't have any ways to study those right only when you have a tool to like change the function or alter the function of these proteins you can study them so people have been like actually trying to make these molecules or even like isolate them and then try to probe how these like different ion channel work and then like I mean until today people are doing that and these things because the the function against these like receptors they can actually be developed as therapeutics and there's one kind of toxin I think it's like anagisia anagisic agents like people use that to treat pain like up until today actually there are like a big group of people like including many from 30 companies they're trying to develop like like molecules including like small molecules also these kind of small protein molecules to target the specific like sodium channels to treat pain and it's like there are some I think there are some clinical trials going on and I expect there will be there will be future therapeutic for that damn so there's biology biology evolved a snakes scorpion spiders all those stuff to have some of them have a most of them have it most of them have most of them has it yeah a protein molecule that many different ones that the many different ones not just one across them they're just wow and and uh and it's so it evolves so that they themselves could um once they bit a mammal like like a rodent like a like a rat or like a something like that yeah um that works against all mammals I guess it works against all potential mammals yeah and then as soon as it but then that would paralyze it or something along those lines and then they could then eat it uh and whoa so okay so then we have the potential to take that out of the creature and then begin doing tests on exactly where how that um causes the harm to us and then we can then um engineer strategies to prevent that from uh working and so I do believe there was another company that at Indie bio that I was um helping as well in one of the batches of the nomics that was doing some uh interesting assisting for people especially in parts of the world that have these venomous uh creatures um to prevent them from getting the the venom uh issues arise I think that's because there's there's I believe it was in the millions of people worldwide because there's all different types of venomous um yeah yeah yeah yeah and so okay then it was um this is great you came to San Francisco yeah yeah to UCSF for his postdoc yeah he came over to Silicon Valley and that was for four years doing computational protein design for new protein structures yeah okay so teach us about this so also like computers are now able to do protein design yeah so yeah so after I did my phd I learned like all the technologies of protein molecules right there's there's just like you can name a protein I can synthesize it any any maybe not any but most of them most of them yeah so I got the technologies to synthesize many of the proteins right and how many proteins I synthesized are there or yeah are there yeah so in human body there are about 20 000 genes that encode like 20 000 proteins in human body is it a one-to-one ratio uh the genes means like open reading firms means one gene to one protein about some of the different cells like some of the protein got expressed other proteins may not be expressed but in total people have these many proteins that that could be expressed in human body but each specific cell I'm not sure I'm not sure yeah but total amount like that and maybe even before we do the computational protein design yeah we're starting a venture into this and I think it would be helpful to to also like break this down a little bit more so okay people are pretty familiar with at least they understand DNA most people at least get the DNA and then we have the nucleotides in the DNA AST season G's and then this acts as a code within us that can then be used to make amino acids which then make proteins and amino acids are in chains right and those amino acids then fold into the proteins okay and the body is all all there's like never so there's literally never a moment your whole life your body's constantly reading these letters of DNA uh making amino acids putting them into chains make having those fold into proteins to do things for you yeah all the time all the time every minute every second every second yeah it just keeps going like I mean protein as a eventually the functional functional players are like all human activities let's list yeah list some of these functional activities that proteins do with the human body yeah right like like the ion channel is just talked about like when the neuron we have the like when I move my hand right the new your brain needs to send a signal to my muscle to the muscle and then the muscle receive the signal then like my hand can move I can see you these all function like at the protein that like in the neurons there are like these ion channels and when you give a stimulus of the ion channel the ion channel opens and then it gives you like like an electronic signal and this is an electronic signal passed down through the through the neurons through the axons and they eventually pass to your muscles and then like your muscle can move so proteins are a massive part of our nervous system they're in every single one of our cells of our brain of course every cell yeah every cell in our body has every so many proteins are in every cell of our body like thousands of proteins more of course more more than thousands of proteins in every cell I think more than millions oh my god I'm not sure like how many but it's it's full of like it's full of proteins like if you think about if you think about a couple couple water right like the water filled up the cup and then it's all with like these water molecules in the cell it's like similar situation whoa all these different proteins they pretty much filled up you're like your cell yeah so a so a filled up cup of water has H2O molecules just all around yeah and then the cell also has filled with different biological components right it's filled in it's all filled up it's not it's not like there are empty space here like the room you get some empty space in the cell there's no empty space technically this is also like I mean right yeah yeah so technically there is no empty space there is no empty space what I mean yeah yeah if you think us like like proteins yeah if you think of this room like a cell right yeah and us like these cameras there's been protein molecules it will not be this situation in the in the cell it's what we feel the impact yeah it will be filled up like you and me and these stairs and everything yeah yeah I mean interact with each other all the time yeah yeah so so this is interesting so the just like there's an encoded sequences in our DNA to then make the amino acids which again there are encoded sequences of amino acids which make specific proteins there's somehow proteins are smart themselves and then the cell is smart itself people think okay well it makes sense that a cell is smart at least you know it that one we've had some episodes where we've talked about the intelligence of the cells but yeah but the protein inside the cell is intelligent it knows what's happening in the cell outside like yeah I don't I mean this if you really think hard and then if you really think deep it goes to it goes to back the original life right heart of life got evolved heart of life become possible like all these protein molecules it got I mean from evolution it's it's it's all get evolved to like up until today but then like how they start in the beginning I'm not sure if people know that like it starts in the beginning there's only this like as molecules like there's no life there's maybe there's no there's no proteins and then somehow it got it gets evolved and then like bonds make bonds and then you come up with these like small maybe smaller segments and then somehow these smaller segments assemble together and then at one point you form cell but then how why why things work like this like how did protein go evolved like to have this function like now we have like so many proteins have so many different functions but why why I don't know I don't know I don't know if we can come up with a solution to that how we ended up with 20,000 yeah how are you like how we end up being like what we are yeah yeah I don't know I don't know about I don't know how to figure that out but like I mean people have been doing research like to see like how the simple things become like complicated things and there's lots of people working on the simplicity evolving to complexity and simulating that process yeah which is so fascinating yeah and then we ourselves could potentially launch another simplicity again and watch it evolve and trillions of them just watch them evolve yeah it's such a beautiful beautiful creation yeah maybe yeah if we understand enough of this system right if if eventually if eventually we can understand the system maybe like you have isolated bugs you give the basic elements and then you feed the information that you know that you learned from all the system maybe in this isolated box you can evolve a life form that'll be so cool right yeah exactly yeah yeah okay now that's that's far away from the topic this is it's right there with the biology and evolution and how proteins were so so now how how how did we let's let's also let's also hit this one along the way how did we figure out the individual components of the cell as well how many years ago was that oh that started a long time ago 50 years ago more than 50 more than 100 100 yeah must be 100 and and i'm not a cell biologist like i can't i can't tell you two specific things on that but it's been a long time and and i mean like yeah 50 60 years ago people figured out the DNA code exactly Francis and Crick yes but before that people know there are people know there are DNA there are proteins people knew there was there are DNA's i mean people can actually DNA and proteins but they just don't know how it works it's understanding the mechanism is different than knowing the molecule exists right oh so we figured out the molecule existed we knew that for a while but we didn't know how the mechanism yeah i mean i mean Francis and Crick they solved the DNA structure that's how we know how DNA how how DNA work but before that i mean people how i said it's the DNA's otherwise they can't have the DNA to get the structures so that goes now now i'm back yeah and then so then most recently then we figured out that that proteins in a sense are kind of like building blocks there there are different proteins that couldn't that do different things within our bodies that are critical to the functioning of life and then then there's launching the computational capacities now of silicon and chips to be able to to do design to designs yeah okay so is this mean like there's like a natural biological does like there's 20 000 protein designs that uh for for for all of biology or for just humans no for humans it's 20 000 but other lives maybe maybe bacteria they have different number of proteins have different yeah because that's where we that's where we find crisper cas9 yeah yeah so we can still find really cool things and like bacteria so bacteria bacteria might have maybe more like tens of thousands more you think i mean some of the protein will be similar they might be homologed but there are different ones i mean many of the like biotechnology were actually like intrigued or like partially contributed by these algorithms like the PCR reaction the DG polymerase the design that the the the real pc the real DG polymerase that make PCR work were isolated from i think archaeos it's not from human human polymerase doesn't work like that yeah yeah well yeah yeah okay and then then now there's a natural let's say in both microbial plus human right etc more evolved life earlier life and later evolved life there's an array of proteins that exist and then there's ones that we make that are not found in biology right yeah yeah because like for to make the like the truly normal one that's not found in nature i mean it's possible to do that now at this moment because we have the competition of power to design proteins like to design the structures that we want like if you have a protein structure that you want to design you need pure computational approaches you can do that now it's totally possible and you were doing this at UCSF we did that at UCSF for molecule like we designed a protein molecule that has an unnatural component to the protein we designed that to have the unnatural component and then after we did the design we actually we actually did the experiment to validate if the design works successful or not so eventually determine the structure and turn out to be like pretty much the same as we designed so the protein design community is actually growing pretty fast now and we are at the point that we can design protein structures like if you want to design structure we can do that but the problem the challenge is now people are facing is to design the proteins with the embedded functions like if you want to design to do the enzymatic thing like to cut peptide bond or to stage peptide together if you want to design that that's hard that's real hard because protein function when protein function it's a dynamic process it's not like a solid rock right it's not just sit there and do nothing it actually moves around and do things but how you design this dynamic thing it's really hard but that's the that's the thing the scientists are doing at this moment so okay so then you got your understandings of computational protein design and chemical synthesis you got your footing in those and then you were like okay i'm going to take this opportunity to come to west lake right okay so now tell us about the transition to west lake how did that come up after the postdoc and why did you take the opportunity and what are you guys doing now in the lab yeah so we had to go to postdocs at some point you realize you have too many ideas to the point that you just have too many ideas you can't work on the work on every single one of them right at that point you know maybe it's time to move on maybe it's time to just start your own lab and get people and work on those things right so that's pretty much how I felt when I was finishing up my postdoc and looking for academic jobs and then for me I thought I mean the reason why I go back to China is one thing is because I'm Chinese I grew up in here I like the things here I mean I like the US too but I thought eventually I probably won't go back to China so that's one reason another really is like China is investing a lot in science so attract like global talents not just Chinese like across all nations so I saw the opportunities so I took it and I thought with the resources we have here I will be able to do the things that I want to do so at west lake my research group has a few different components one will be like on the protein chemical proteins in these parts because there are I mean people have been working on this for like a about a century all the way back from like imeficial make that that peptide bond to like octetosine synthesis to like solid phase peptides and then lithium chemicalization to make proteins but at this moment it's still hard to make it's still hard challenging to make real protein molecules that's like a big size like the biggest one we made up until today it's like less than 400 amino acids now the peptide chain less than 400 amino acid that will take years to do okay well let explain this to is a is a peptide in an amino acid an amino acid is a peptide no a peptide is a chain of amino acids okay so so a peptide is a chain of amino acids and you are giving this example earlier where it's hard to make a synthesize a protein that can cut a peptide no to to make a protein that's like 400 that's now I thought I was mentioning earlier but okay yes yes so so currently most of the proteins that are made by our bodies are made with amino acid chains peptide chains of 200 300 no so the if you think about so proteins could some proteins they have just one function domain which means just one thing any function so that size will be around maybe 200 300 amino acids if they have one function if they have one function a domain some proteins they have a bunch of these things wow so they become really big yeah like our channels we talked about yeah it's over a thousand amino acids now like the DNA palm trees we talked about the people using the lab pcr it's over a thousand amino acids now wow I mean those are those that beyond beyond the technology we have at this moment but we are synthesizing to 300 we are yeah chain amino acids and in they're folding into proteins yeah they will fall into protein with high efficiency right now with high efficiency right but it still takes time like if you want to synthesize a protein of like 300 amino acids it's not the thing that you can do in a week or month it probably takes a year or even longer to do it takes a year yeah why it's just like I mean it's just like you need to I mean when you think about protein synthesis you are starting from the individual component you start one amino acid you do the second you do the third you make a peptide chain which may be like now 50 amino acids now but that's not big enough right proteins like 200 300 you're only making like 50 40 yeah so the the technology to do that is just you make the bunch of them and you make the individual pieces right you we can't can we computationally make those can I like assign a robot to make that we have robots yes we have robots I mean we got the robot here they make the chains for you but then you need to stitch the chains together oh there's no humans still have to stitch the chains yeah we have to do the reactions and then doing the purifications why can't robots do the change stitch the chains and do the purification right we haven't I mean we do have a knot we just don't have it like we don't have one yet that stitches like there are things there are things you need to think about when you do this can it's all chemistry but you need to think about how to do this chemistry it requires a lot of engineering I think it will come up yeah yeah I might spend some time on that that's an interesting one yeah but uh I mean but there are there are other ways to go around that okay yeah and like how to how do you fish how to efficiently make the proteins like a big size beyond 300 amino acids and you have to stitch the peptide chain so they actually they actually make the natural natural bonds natural bonds right how do they bond how do the peptide chains bond so it's it's amide bonds it's amide bond between peptide but the the the reaction we do now it's actually emitted by my phd divisor so we call it native chemical ligation so right you have a you have one amino acids on the antennas which is we call cysteine the other side you have a because our ester so just develop them together in water and then they just come together wow that's it pretty simple but how do you if you want to have like seven eight pieces of all those things stitching together there are a lot of it it become complicated yeah so that's why it takes time and that's that was for one protein now okay one yeah right okay so and now we we want um proteins that have like a thousand amino acids because they do like five or they do more things yeah there's like like for example in this in this community people are trying to synthesize the mirror image version of the proteins like why we do that one thing is that if you want if you make the mirror image versions maybe you can explore maybe the just a different universe of life i mean people from xinhua university did they did excellent work on that and more there are more people i believe are working on that too like eventually if you can make if i'm chemically synthesis this mirror image proteins even like creating a mirror image life i don't know i don't know how relevant that is to the thing we're doing now but i thought it's really cool yes you come up with that you maybe you can see how that interacts with like the natural things probably pretty that'd be pretty fun i think another reason is there's one direction people are doing is we try to make mirror image protein therapeutics which is totally unnatural like the human human body never saw we're trying to make a protein the human body's never seen never seen and use that as a therapeutic right okay yeah yeah it's like uh you know okay i mean longitudinal testing yeah yeah yeah i mean they might just just go into the body and do the thing and then just don't cause anything but we have to make sure it does the thing of course of course you of course need to go through like a early development and then doing some animal studies yeah eventually maybe doing clinical trials and people including like my peer advisor they've done some other work but still it's still going up this field is there a chemical that's is there a is there a protein that's been chemically synthesized that is already being used in the FDA no not yet this is like a new thing this is a really new wow that will be very profound for the first one that gets approved yeah it will be really it will be really cool yeah yeah whoa so if you think about that if you want to develop that kind of protein therapeutics you have to it gets a little bit complicated you have to actually make the mirror image version of the natural proteins to do that i can't explain two details but it's actually a requirement you need to make the natural protein target at the mirror image version to for you to be able to develop that kind of therapeutics so you can't get away from making the mirror image protein molecules if you want to make that how do you make that you need new technologies that's what we're doing and so then is it that even the the the chemically synthesized protein would still need to have the mirror image of the one that's inside of our body because it would need to potentially do the effect it wants to do through that protein yeah so so the mirror image therapeutic we eventually come up with right it will interact interact with people so they will interact with the natural things yeah yeah okay yeah how does your lab figure out what proteins it wants to chemically synthesize there's obviously so many unlimited options so yeah how do you guys figure this out yeah so we have to work with the biologist like that's also the reason why i joined the school life sciences at west thick universities so most of the like for most of the therapeutic developments i think the biology most of the time of the biology goes first like i mean especially for the targeted approaches you have one you need to develop the maybe a signaling pathway like or like a therapeutic target you have the target right and then you try to develop molecules to work on the target like targeted therapeutics like now like immune checkpoint inhibitors like those are focused on the specific targets so you have do you have this target and then maybe you work on this target for us we'll collaborate with the people at the life science like life science school of science at west thick university and other people's too other people too and we will see like which molecule which target is the most irrelevant like therapeutic target or it's the most like medically unmet like needs for the patients before we identify that first and then we use other approaches we have do you have any ideas what those targets might be i mean our channel is a big one for sure iron channel yeah our channel is a big one i've been working on channels like for a long time so our channels obviously like pain management is only one thing epilepsy other things too okay iron channels related to pain management epilepsy a lot of things and like autoimmune disease there are a lot of these related to our channels like in immune cells there are channels there are channels to regulating the immune cell okay so so uh chemical protein synthesis could be used for immunotherapy they well it can develop the molecules that's used for immunotherapy because for immunotherapy now for the immune track points it's antibodies antibodies attract the most attention but i mean there are other ways too like to go around antibodies and i think like the current situation with antibodies is just it's too hot like everybody's working on antibodies i mean of course it's great so many drugs who so many antibodies have been like approved but i think people also needs to focus on other classes of protein molecules to try to come up with different ways to treat the disease right if everybody's working on this one thing like eventually i don't think you can fix anything so i mean disease cancer it's all it's all a complicated process you have to have multiple ways or multiple strategies to come up with one thing with to come up this and then and then come up with strategies to treat the disease so i don't think i think people need to brought out yeah so let's so then let's talk about then the tools so then let's say that you identify your ideal targets then you come with your suite of tools right what's in the suite of tools yeah so now there are there are different approaches we can do these approaches all in our lab see if you have a target you can do computational design actually to design the protein molecules to to like bind to the target or inhibit the target and you start from protein design or you can start you can just do protein selections high throughput protein selection which involves protein evolution you just do the evolution using different systems to come up with the lead molecules right oftentimes the things you have in the beginning like the things you design or the first thing you evolved it's not it's not the perfect one maybe the selectivity is not that high which will give you set effects or maybe it's not stable enough so that way it requires further engineering and then the chemistry can come together come along so the chemistry that we are working on can help you to mix the protein molecule more stable more selective it's just a combination of these all the things and hopefully in the end you come with this lead molecule that's like selective potent and what's that so what would it look like if we were behind the screen right now and you were showing us how you use a computer design to make yeah proteins yeah yeah so to design I mean it's called structurally based design you have the structure of the target protein right oftentimes you figure out the active site like the surface which part of the protein surface like like like us like this part works on or use the arm works on work maybe you'll figure out the arm of the protein and that's the function part and then you see the shape of that you try to come up with complement surfaces like my hands it wraps around this here right so I have to come up with the structure that has the hand shape to bind to here and then you can hold your arm so we use maybe we come up with the finger finger finger different fingers we have a palm and they roughly place them in there right and then you use the computational approaches to just to stitch these different things together and then they hold up together eventually you did that hand and they grabbed there they don't let go yeah yeah that's that computationally that's the basic concept is is there a is there parts on the surface of proteins that are harder to design for sure than others yeah for sure yeah so traditionally for small molecule drug discovery we have to they require the protein surface to have a pocket pocket means like I don't know like you have a dense oh just a pocket right here right and then the small can go in there and go in there if it goes in there it has a better chance to fit in there and then don't let go but now like for many many more targets we identify today it's just like here it's flat it's a flat surface so the small molecule it doesn't have enough of a surface area to interact so it doesn't bind yeah so you can't come up with therapeutics with small molecules but with proteins because you can design these things like have a really big surface area so each part of the interaction might be weak but if you integrate all these things together it becomes really strong it will bind and previously we were trying to get molecules to bind and if it was a region that didn't really have that dent or that area for it to go to plus it has to be so precisely targeted that it goes to that exact dent that area so do proteins kind of have like a more rugged like it could have different shapes it can be smooth it can be smooth it can be really smooth it can be rough some of them we can have like pocket because they bind the different things to function if they have a pocket you can just go to the pocket and then you hit the protein activity but other times just the surface there's no pocket how do you how do you work on that you just have to have like big protein molecules like antibodies and to do that okay okay oh antibodies are big protein molecules huge huge antibodies are huge huge yeah like how many times bigger than the protein well antibody uh let's see antibody has roughly 1,000 and uh maybe 1,200 or between 1,200 amino acids to 1,500 1,200 to 1,500 a small molecule maybe just a few amino acids size so it's a hundred times bigger whoa yeah yeah and around the size of our biggest proteins no oh well protein there are bigger ones we have like 5,000 amino acid proteins yeah there are some of those but some of those they are not just individual proteins they form complex to work yeah but antibodies are pretty big antibodies are not just a single chain either it has different components different component chains yeah yeah and um the antibodies role within our body is immune system right yes yeah it's to identify pathologies yeah as they're bind to those and bind to the oh bind to the pathologies yeah so they so they cannot trigger any like inflammation or like immune response or whatever oh yeah and antibodies originate from what part of our body B cells T cells B B cells B cells so T cells go and hunt for the right and B uh huh these cells it's a little bit complicated like you have if you have an antigen right i'm not immune immunologist if so i don't see too much yeah yeah just even a little bit yeah so like like my antigen got inside the body like they're like dendritic cells like they just uh they just uh swallow these antigens and then they present these cells on the surface of these dendritic cells yeah and the T cells will interact with dendritic cell and then maybe they can get activated B cell will be involved the two during the process launching antibodies but eventually the B cells will secret the antibodies interesting yeah what an incredible machinery the body is okay and then let's talk about um like is there one software that is the best for protein design right now yeah there's one it's uh it's called Rosetta from DBB Collab at University of Washington this is your advisor your no no he wasn't your advisor we collaborated we well the work i talked about we we collaborated with him okay okay yeah okay but Rosetta has been really powerful Rosetta is the best by far right now of well i mean it's the most popular one it's the most popular it's the most popular yeah okay yeah and so is it kind of like Legos like it's kind of like click and drag little a little amino acids well it's a little bit more complicated than that because i know it's not a five-year-old playing Legos on the table yeah yeah they're just different pieces i mean like like i said we want design protein right you have like these fingers palm you have this you need to have some component to start with yeah and then you can try to see how to place these components yes yes and then eventually how what kind of shape you want to make yes yes so based on that you try to collect them and then maybe you have other things to to to make sure they go to this shape but then like for the software it's like it's different modules just try to use different modules okay so this modular yeah yeah people don't need to write all the codes for that you just need to learn to use the modules so it's a little bit like click and drag in that sense but then you still have to shape it the exact way you want it you always need to see what the outcome of that right you have a design you run the you need to run simulations yeah and then you see you you can see the result of the simulation and then if that makes sense okay so you've imaged the target protein and you know where you want your your computer designed protein to go and target that specific area on the target protein and then you design via the computer software the program right and then you then you basically run the simulation of did it work no it didn't work okay you can simulate that and then you go okay let's adjust it like this way and then it's like did it work yeah ah it worked better yeah and then uh so is it literally like that it's like that yeah you just keep tweaking this you have to go you can do a well I mean oftentimes you need to do a few rounds yeah I mean each single time it's not just one output you have thousands of like tens of thousands outputs you just need to you have to come up with strategies to rank different things and then evaluate the results so yeah I'm making such an interesting connection right now from another um simulation software it's used in engineering like in manufacturing yeah they have like a specific part in like a car or a plane or whatever and they they they designate like the parameters that it needs to that it needs to be able to hold a certain amount of force all this kind of stuff it's made of a certain material right yeah yeah and then the engineering simulation will go through just billions of permutations so fast and come up with the best possible solution for that limited space I think it's comparable yeah I think it's comparable customer design we actually I mean we roughly know these modules right we don't we in the beginning we we don't name it we don't we're not sure which amulet which specific amulet to put on there so while trying to go through this whole process to see which amulet is the best what's the best choice at this spot at that sequence and then how to make these connections so you have to go through all the possibilities to to to eventually like make this work it's so fascinating thinking about being able to leverage really powerful biotech simulation to find the most optimal chemical protein synthesis that gives you the exact function that you want it to do within a therapeutic effect on the body yeah I mean like yeah you design that then you design that you probably you might need to evolve that too and you also you can also synthesize that in the year that too it's it's all complementary so it's it's just a complementary approach that it might help another and then so part of the biosimulation is that you make the ideally chemically synthesized protein and that it ideally targets the exact location it's supposed to in the body so like you have to run the biosimulation on that part and then you have to if you could it would be ideal that I could literally run you I have would have your exact yeah tens of trillions of cells of your body put together you know into this is you know a digital twin of bubble dung and then I can deploy my chemically synthesized protein into your body and see digitally right on the digital twin version before we do it on the physical version and then see if it does the exact therapeutic effect that we want it to do and we can run that billions of times to make sure it's safe or fast forward 20 years see if anything bad has happened you know that's like science fantasy yeah science fiction yeah I mean if you can if you can do the simulation at the cell level I'd be so amazing so amazing yes because it's it's just so complicated because like when you do simulations or like designs you have to consider every single atom the movement of every single atom yeah like think about how many atoms are there are in one protein molecule one protein molecule like think about how many proteins in one cell and it's not just the proteins they're all things too yeah but people can simulate that it's so funny looking back 100 years like it in 100 years if you look back at this video content and you go look at them talking about how hard it was to make a simulation of a cell exactly like if you think about like like 100 years ago when people start to make peptides yeah even make like peptide like four five amino acids long 100 years ago it's not possible like maybe 60 70 years ago it takes so much effort like the first though first the chemically synthesized insulin that was made it roughly 50 60 years ago that took maybe 100 people like five five years or maybe even longer to make that and now we brew insulin just now myself if I want to make that I can make that in like one two one two weeks just me myself just you by yourself can make insulin one or two weeks in one or two weeks yeah yeah exactly the whole brewing insulin market yeah yeah but the insulin in the market it's it's already coming to express that it's not chemically synthesized it's not chemically it's not chemically synthesized because insulin is actually a little bit a little bit tricky has two different chains but two different chains have like they have they need to be linked to correctly together yeah to function yeah so I mean for the production cost view I think it's actually people are doing that recombinantly because people insulin it's like it's one part of the human so we can we can express that pretty efficiently I love the points about like both democratizing chemical protein synthesis so that we can let people be creative and use their creative talents and try and solve these big health um challenges uh but also ethically evolving and consciously spiritually evolving so that we don't put chemical protein synthesis into the hands of people that can cause bad protein synthesis yeah that could that that actually could happen if people want to do that yeah this is very important yeah yeah because it's I mean the technology it's not if you want to something if you want to make something bad it's it's not that hard yeah yeah you said you could make insulin in one to two weeks yeah you know and it used to take uh team hundred people and you know all this stuff before and so like look at how much faster it's going down and down and down and yeah yeah I'm just going to be able to download the the bad thing from the internet in the future and just have it be made by a robot you know yeah I mean the societies have just needs to have regulations on these things like I mean we can't control the individual behaviors of every human being but then like we have regulations we have laws people follow the rules if you don't then you get published but uh it's I mean you kind of somebody can actually take these technologies to do something but uh I like to think about it like needing to evolve ourselves consciously faster so that we don't have those oops moments and then we don't need these extremely strict regulations and laws also that yeah that sometimes can hinder creativity maybe people just need to educate education is a big part of it is a big big part of it yeah yeah let's do a couple quick questions on the way out that we like asking our guests what would you say is the overall meaning or purpose of life hmm overall meaning of life I think it's about explore the unknown territory in every aspect could be in science could be in nature could be like consciousness like people want to know what the basis of memory what's the basis of consciousness I think I think the meaning of life is just is to understand these things and then maybe know where where where where we come from it's hard to figure out where we're going because but figuring out where we come from maybe it helps learn from the learn from the past but it's it's it's I think it's all about exploration like you need to have the people need to have the spirit to go out and do things I mean need to they actually need to believe in the things that they might be able to do I mean you may not necessarily be able to do that in your lifetime but I think it's actually important to have the belief that you can do something you can achieve something through this life I think that's that's actually key I like I mean I'm a big fan for all climate I'll climb a lot like the spirit is it's it's the same like you have to go explore and then explore the limits of yourself maybe that will partially explore the limits of the human race I think for people if people all have this mind side and then it will be the life for I mean the society will be more diverse like and we need to love these these behaviors people need to support each other on this so I mean myself like I I just like the spirit so I'm heading to all that yeah pushing the boundaries of what is known pushing the edge of knowledge further and further going into the unknown venturing out there yeah life become more interesting if you do that otherwise it's so boring it could be really boring for life so yeah what about a skill that young people should know going into the exponential technology age the skill it's hard to see the one single specific skill I think it's more maybe it's more about the mindset you have to you have to cope you have to keep your mind open like things are changing all the time you know you can't just rely on that you can you acquire this single skill and then you can just you can just like you can just go out and then like do everything it's not possible you just you need to keep the mind open and then see what's happening in the world and then see maybe how you can contribute to this world by doing the things that you can do or maybe pushing it further to explore the things you haven't thought about so I think the mindset is actually more important than skills and how can we inspire more people around our world to collaborate yeah I like collaboration for myself I just like to work with people and especially if you're happy we work with people and then make things work how to educate I mean it's a long process like maybe the whole society needs to make the effort in there like like through schools and then through the working with people I just think people need to be more open and then eventually if the openness will will leads to trust in people then I think that will that will definitely help with that but like how to how to get people more open it's it's it's like a society behavior like I mean people just need to talk with other people support that support people so if you do I mean if you see things differently I like that like the things in the U.S. don't judge right so you have to keep your mind open then we need to share with people share the knowledge to share the skills educate other people and if everybody makes a little effort on that end I think eventually people will have more trust in each other and then maybe collaborate together yeah I think that's my thought yeah what do you think is the role of love in our world it's critical apparently yeah I mean human I mean not just human all life forms essentially eventually it's reproduction that's like I mean that's the driving force if there's no reproduction there's no driving force for the for the for human or for life form so love love could be like lovely just like I mean reproduction is a direct result from from love I mean love can be other things too like love can mean like just like you go out on the street like talk to people like encourage people encourage people to explore the underworld it's encourage people to do the things they can't do or maybe encourage people like they have difficulties in life so it's critical people used to have love for yourself for other people for the world do you think that this is a simulation I think about that actually sometimes like you go back home right how can you tell like how can I tell the things that the world we are living in is not it's not a dream right I mean we feel everything right we talk to people the thing is different but then I mean it could be a dream when you dream when you when you're living your dream it's like the same you feel you don't know you're dreaming right sometimes you wake up and then you feel oh I was dreaming but maybe this whole thing is a dream it could be but it doesn't matter right whether it's dreaming or not you still do the thing you want to do you still explore all the things you want to explore you're still trying to push the people you want to push educate the people you want you want to educate and then love the people you want to love so I think it doesn't matter and what do you think is the most beautiful thing in the world the most beautiful thing in the world I feel it's like I feel like the people have the spirit to do the things that they were not sure if they can do and sometimes you they are actually willing to sacrifice for that I don't know why people want to do that but people can do that and there are people doing that I think that's so incredible you can't explain right I mean if you want to if you want to if you want to live if you want to live just just keep you keep alive there are so many ways and then it's also a basic instinct to keep yourself alive but then there are so many people trying to push the boundaries and then sometimes it costs it costs the life even but then people still have the spirit to do that I don't I mean it's hard to explain but that thing I think that thing actually makes you feel your life is fulfilling you are teaming you are you're you're you're not proving to you're not proving to you're proving to other people that you're worth it it's just like it's just a matter of yourself like I want to do that and I feel happy doing that so that's the that's the reason I want to do that and I will do that and I think that's the thing yeah we really love calling it like the burden of genius that you take on this amount of responsibility and you just go and bring this unique gift to the world and it's just such a gorgeous feeling and experience to go through that journey and to bring value yeah yeah yeah sometimes you may not know clearly you're you're creating some value but you are so people need to do that yeah and encourage encourage others yes for sure yeah but this has been such a pleasure thank you so much for talking with him on our show really appreciate it thanks for all your great work yeah good job thanks everyone for tuning in we greatly appreciate it we'd love to hear your thoughts in the comments below on the episode let us know what you're thinking have more conversations with your 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