1 00:00:00,790 --> 00:00:07,320 [Music] 2 00:00:11,470 --> 00:00:09,120 [Applause] 3 00:00:14,260 --> 00:00:11,480 thank you guys for coming thanks for 4 00:00:15,880 --> 00:00:14,270 inviting me you guys I'd like to 5 00:00:19,030 --> 00:00:15,890 announce that the next apps icon is 6 00:00:20,710 --> 00:00:19,040 going to be at Georgia Tech and it's 7 00:00:23,530 --> 00:00:20,720 gonna save us a lot of money and air 8 00:00:26,019 --> 00:00:23,540 fares and hotels these are all the 9 00:00:29,940 --> 00:00:26,029 Georgia Tech people at this meeting or a 10 00:00:34,569 --> 00:00:32,109 okay I'm gonna talk about biopolymers 11 00:00:35,560 --> 00:00:34,579 and you guys my time doesn't start yet 12 00:00:40,150 --> 00:00:35,570 because it's kind of background 13 00:00:40,750 --> 00:00:40,160 information the the this this new 14 00:00:42,670 --> 00:00:40,760 mission 15 00:00:44,740 --> 00:00:42,680 you know the dragonfly this is like so 16 00:00:48,670 --> 00:00:44,750 good for us right this is we're going to 17 00:00:50,650 --> 00:00:48,680 a planet with polymers and organic 18 00:00:53,620 --> 00:00:50,660 chemistry this is going to be really 19 00:00:55,900 --> 00:00:53,630 exciting for all of us here okay so I 20 00:00:58,180 --> 00:00:55,910 want to talk about polymers you know 21 00:01:01,090 --> 00:00:58,190 like does biology actually need polymers 22 00:01:04,439 --> 00:01:01,100 and our biopolymers special among 23 00:01:07,270 --> 00:01:04,449 polymers and what can we learn about 24 00:01:08,770 --> 00:01:07,280 biopolymers you know about the origin of 25 00:01:10,450 --> 00:01:08,780 life what do biopolymers actually tell 26 00:01:12,010 --> 00:01:10,460 us about the origin of life and when you 27 00:01:14,649 --> 00:01:12,020 think about biopolymers of course this 28 00:01:16,570 --> 00:01:14,659 is sort of where we start which is 29 00:01:18,550 --> 00:01:16,580 really you know this is information flow 30 00:01:22,720 --> 00:01:18,560 in biology right there's sequences of 31 00:01:26,080 --> 00:01:22,730 DNA that's information is is transcribed 32 00:01:28,240 --> 00:01:26,090 to RNA it's translated to protein and 33 00:01:30,219 --> 00:01:28,250 then protein actually does things with 34 00:01:32,890 --> 00:01:30,229 that information so this is all about 35 00:01:36,250 --> 00:01:32,900 information and information is sequences 36 00:01:39,399 --> 00:01:36,260 of monomers that are linked that's 37 00:01:43,210 --> 00:01:39,409 really essentially what polymers are 38 00:01:45,370 --> 00:01:43,220 about so isn't it really important to me 39 00:01:48,090 --> 00:01:45,380 feature polymers is that they are all 40 00:01:50,920 --> 00:01:48,100 made by dehydration condensation okay 41 00:01:53,410 --> 00:01:50,930 everybody Universal bio polymer is made 42 00:01:55,240 --> 00:01:53,420 by essentially the same chemistry which 43 00:01:57,190 --> 00:01:55,250 is you take two monomers you put them 44 00:02:00,010 --> 00:01:57,200 together and a water molecule comes out 45 00:02:01,120 --> 00:02:00,020 and there's a lot of other things that 46 00:02:02,740 --> 00:02:01,130 are universal they all go through 47 00:02:04,570 --> 00:02:02,750 phosphorylated intermediates they're all 48 00:02:06,160 --> 00:02:04,580 made by possessives motors that use 49 00:02:08,380 --> 00:02:06,170 divalent cations there's a there's a 50 00:02:10,270 --> 00:02:08,390 whole lot of universalities in bio 51 00:02:15,789 --> 00:02:10,280 polymer synthesis but i want to focus on 52 00:02:17,949 --> 00:02:15,799 this water element here this is the way 53 00:02:20,770 --> 00:02:17,959 i think about it which i think you 54 00:02:21,760 --> 00:02:20,780 should think about it which is that you 55 00:02:24,340 --> 00:02:21,770 know I'm at AB 56 00:02:26,050 --> 00:02:24,350 is a small molecule that is either used 57 00:02:28,990 --> 00:02:26,060 as a substrate or a product in an 58 00:02:31,120 --> 00:02:29,000 enzymatic reaction and water is clearly 59 00:02:34,360 --> 00:02:31,130 the most abundant and frequent and 60 00:02:36,790 --> 00:02:34,370 universal metabolite in all biology you 61 00:02:40,210 --> 00:02:36,800 use over your body mass of water in 62 00:02:44,050 --> 00:02:40,220 chemical reactions every day so water is 63 00:02:46,960 --> 00:02:44,060 the primary metabolite of biology what 64 00:02:48,310 --> 00:02:46,970 does that mean if we think about the 65 00:02:51,340 --> 00:02:48,320 surface of the land now I'm talking 66 00:02:54,490 --> 00:02:51,350 about NIC HUD kind of ideas here that's 67 00:02:57,240 --> 00:02:54,500 so where they come from is the activity 68 00:03:01,240 --> 00:02:57,250 of water on so on the entire planet 69 00:03:03,910 --> 00:03:01,250 cycles every day so reactions that take 70 00:03:06,340 --> 00:03:03,920 up and and release water are pushed and 71 00:03:09,250 --> 00:03:06,350 pulled on the entire planet every day 72 00:03:11,620 --> 00:03:09,260 except in certain places and that's in 73 00:03:13,060 --> 00:03:11,630 large bodies of water that is that that 74 00:03:15,580 --> 00:03:13,070 is a place where the activity of water 75 00:03:17,170 --> 00:03:15,590 is constant and and we're not going to 76 00:03:20,500 --> 00:03:17,180 be able to push in pull reactions by 77 00:03:23,230 --> 00:03:20,510 this process so the abiotic synthesis of 78 00:03:26,500 --> 00:03:23,240 polymers by the cycling of water is a 79 00:03:27,850 --> 00:03:26,510 metabolic process and think about what 80 00:03:31,450 --> 00:03:27,860 Moran was saying if you were here for 81 00:03:33,880 --> 00:03:31,460 her talk early you take monomers you dry 82 00:03:35,680 --> 00:03:33,890 them down you make polymers and you 83 00:03:37,810 --> 00:03:35,690 bring them back up into solution and 84 00:03:39,550 --> 00:03:37,820 there kinetically trapped so what you've 85 00:03:41,650 --> 00:03:39,560 done is you've taken sunlight 86 00:03:44,350 --> 00:03:41,660 effectively and you have incorporated 87 00:03:46,030 --> 00:03:44,360 that energy into chemical bonds okay so 88 00:03:47,920 --> 00:03:46,040 that that is basically what the dry down 89 00:03:49,930 --> 00:03:47,930 root reaction does it's taking 90 00:03:51,610 --> 00:03:49,940 environmental energy and it's putting it 91 00:03:53,680 --> 00:03:51,620 into chemical bonds and you repeat this 92 00:03:55,900 --> 00:03:53,690 process and you can keep adding more and 93 00:03:58,930 --> 00:03:55,910 more energy into chemical bonds okay so 94 00:04:00,700 --> 00:03:58,940 this is this is metabolism to me and 95 00:04:03,130 --> 00:04:00,710 it's it's kind of funny I remember in 96 00:04:05,440 --> 00:04:03,140 the old days Steve and people would have 97 00:04:09,790 --> 00:04:05,450 these arguments about what was first 98 00:04:11,290 --> 00:04:09,800 nucleic acids or or metabolism and the 99 00:04:13,270 --> 00:04:11,300 problem with those discussions I think 100 00:04:16,330 --> 00:04:13,280 was that the way people were thinking 101 00:04:18,039 --> 00:04:16,340 about metabolism was in terms of the 102 00:04:19,360 --> 00:04:18,049 krebs cycle running in Reverse and 103 00:04:21,370 --> 00:04:19,370 things like that but if you think about 104 00:04:24,180 --> 00:04:21,380 metabolism in this way I think it 105 00:04:26,320 --> 00:04:24,190 changes the argument I think Steve might 106 00:04:28,570 --> 00:04:26,330 haven't talked to him about this but I 107 00:04:31,810 --> 00:04:28,580 think he might accept that metabolism 108 00:04:34,090 --> 00:04:31,820 could take a lead before biopolymers if 109 00:04:35,830 --> 00:04:34,100 we define metabolism like this 110 00:04:38,740 --> 00:04:35,840 you don't have to say anything I'll ask 111 00:04:40,870 --> 00:04:38,750 you later over beers okay so now let's 112 00:04:45,130 --> 00:04:40,880 talk about actually it's kind of ironic 113 00:04:46,900 --> 00:04:45,140 that the people who finally discovered 114 00:04:51,040 --> 00:04:46,910 this metabolic process where nucleic 115 00:04:53,020 --> 00:04:51,050 acid people they were naked and and ROM 116 00:04:54,820 --> 00:04:53,030 Krishnamurti and people like that so 117 00:04:57,550 --> 00:04:54,830 that the people who are focused on 118 00:04:59,560 --> 00:04:57,560 metabolism are really interested in the 119 00:05:00,310 --> 00:04:59,570 Krebs cycle and redox chemistry and 120 00:05:01,930 --> 00:05:00,320 things like that 121 00:05:04,600 --> 00:05:01,940 and they really weren't paying attention 122 00:05:06,580 --> 00:05:04,610 to simple chemistry which is hydration 123 00:05:08,920 --> 00:05:06,590 dehydration which is near equilibrium 124 00:05:10,540 --> 00:05:08,930 processes on the surface of the earth so 125 00:05:13,180 --> 00:05:10,550 if we look there then we can see that 126 00:05:16,650 --> 00:05:13,190 it's really easy to imagine metabolism 127 00:05:20,290 --> 00:05:16,660 and biopolymers you know coming together 128 00:05:23,170 --> 00:05:20,300 okay so this is a polymer polymers are 129 00:05:24,340 --> 00:05:23,180 amazing they're magic okay polymers are 130 00:05:28,090 --> 00:05:24,350 magic that's the thing you have to 131 00:05:30,100 --> 00:05:28,100 realize they're undescribable amazing so 132 00:05:31,990 --> 00:05:30,110 if you look inside those things what you 133 00:05:34,480 --> 00:05:32,000 can see this beautiful self 134 00:05:36,610 --> 00:05:34,490 complementarity all biopolymers our self 135 00:05:38,410 --> 00:05:36,620 complimentary if you look at cellulose 136 00:05:40,180 --> 00:05:38,420 all the donors donate and all the 137 00:05:42,310 --> 00:05:40,190 acceptors except if you look in the 138 00:05:44,410 --> 00:05:42,320 center of a protein the donors and 139 00:05:45,970 --> 00:05:44,420 acceptors are beautifully aligned and of 140 00:05:48,250 --> 00:05:45,980 course if you look in nucleic acids 141 00:05:50,020 --> 00:05:48,260 nucleic acid chemists are used to 142 00:05:51,490 --> 00:05:50,030 talking about complementarity but that 143 00:05:54,840 --> 00:05:51,500 complementarity extends to all 144 00:05:57,730 --> 00:05:54,850 biopolymers okay every biopolymer is 145 00:06:00,790 --> 00:05:57,740 itself complementary you can see a Alpha 146 00:06:03,250 --> 00:06:00,800 anti parallel beta sheets and parallel 147 00:06:05,710 --> 00:06:03,260 beta sheets and alpha helixes everything 148 00:06:08,020 --> 00:06:05,720 is beautiful everything is perfect okay 149 00:06:12,070 --> 00:06:08,030 the problem is the same thing is true in 150 00:06:13,090 --> 00:06:12,080 ice if we take a water molecule and we 151 00:06:15,580 --> 00:06:13,100 crystallize that you look in that 152 00:06:17,440 --> 00:06:15,590 crystal you'll see the same thing small 153 00:06:19,420 --> 00:06:17,450 molecules when they form crystals are 154 00:06:21,550 --> 00:06:19,430 also self complimentary all the donors 155 00:06:23,920 --> 00:06:21,560 donate and all the acceptors accept so 156 00:06:26,890 --> 00:06:23,930 the question is really what what is 157 00:06:30,100 --> 00:06:26,900 special about a polymer how is that how 158 00:06:31,540 --> 00:06:30,110 is an Ice Cube different from a polymer 159 00:06:34,650 --> 00:06:31,550 what is the fundamental difference 160 00:06:39,700 --> 00:06:37,720 okay this is this is the difference if I 161 00:06:43,990 --> 00:06:39,710 take I say I take a mixture of 20 amino 162 00:06:46,420 --> 00:06:44,000 acids and I very slowly cool it they 163 00:06:48,280 --> 00:06:46,430 will resolve okay this is called 164 00:06:49,930 --> 00:06:48,290 recrystallization people make money off 165 00:06:51,909 --> 00:06:49,940 of this right this is how you purify 166 00:06:54,460 --> 00:06:51,919 things you recrystallize them because 167 00:06:57,550 --> 00:06:54,470 monomers will resolve in two simple 168 00:06:59,980 --> 00:06:57,560 systems biology doesn't want that right 169 00:07:01,480 --> 00:06:59,990 biology wants enzymes informational 170 00:07:03,640 --> 00:07:01,490 molecules it wants to 171 00:07:05,890 --> 00:07:03,650 it wants to through evolutionary process 172 00:07:08,260 --> 00:07:05,900 put functional groups at specific places 173 00:07:09,400 --> 00:07:08,270 in three-dimensional space okay that is 174 00:07:12,070 --> 00:07:09,410 not allowed here everything is 175 00:07:14,320 --> 00:07:12,080 determined by this small molecule so 176 00:07:18,000 --> 00:07:14,330 there there's no control of that that 177 00:07:21,040 --> 00:07:18,010 biology requires so we want to do this 178 00:07:24,250 --> 00:07:21,050 but nature doesn't let us do that okay 179 00:07:26,620 --> 00:07:24,260 if I take 20 amino acids and I try to 180 00:07:28,540 --> 00:07:26,630 assemble them I can't do it if I take 181 00:07:31,840 --> 00:07:28,550 guanine and cytosine together in water 182 00:07:34,270 --> 00:07:31,850 they don't form base pairs unless 183 00:07:37,050 --> 00:07:34,280 they're polymerized okay the magic is in 184 00:07:41,170 --> 00:07:37,060 the polymerization so this doesn't work 185 00:07:43,300 --> 00:07:41,180 but this works okay with linking things 186 00:07:45,070 --> 00:07:43,310 together and the linkage is really 187 00:07:46,630 --> 00:07:45,080 important okay it does it two things 188 00:07:49,150 --> 00:07:46,640 first there's the proximity it keeps 189 00:07:51,310 --> 00:07:49,160 things close together so the entropy is 190 00:07:53,890 --> 00:07:51,320 much less forming this thing because 191 00:07:55,270 --> 00:07:53,900 these things are already constrained to 192 00:07:57,070 --> 00:07:55,280 be close together in space so there's a 193 00:07:59,440 --> 00:07:57,080 big entropy argument but the other thing 194 00:08:01,690 --> 00:07:59,450 is this you know in biopolymers these 195 00:08:03,900 --> 00:08:01,700 are not flexible strings right these are 196 00:08:07,630 --> 00:08:03,910 very specific for example a peptide 197 00:08:09,969 --> 00:08:07,640 highly restrained pre-organized and and 198 00:08:13,900 --> 00:08:09,979 really already pushing very hard for 199 00:08:15,700 --> 00:08:13,910 this assemble thing in fact any RNA you 200 00:08:17,740 --> 00:08:15,710 make any sequence of RNA except for a 201 00:08:20,350 --> 00:08:17,750 homo polymer and it will assemble right 202 00:08:22,420 --> 00:08:20,360 RNA just wants to assemble so bad you 203 00:08:24,880 --> 00:08:22,430 can't stop it and any sequence of 204 00:08:26,650 --> 00:08:24,890 polypeptide will form beta structures 205 00:08:29,560 --> 00:08:26,660 right so the assembly of these molecules 206 00:08:31,960 --> 00:08:29,570 is built into the backbone in many ways 207 00:08:34,240 --> 00:08:31,970 and it's just totally inescapable um 208 00:08:36,610 --> 00:08:34,250 people complain that they make random 209 00:08:38,709 --> 00:08:36,620 sequences of polypeptide and it always 210 00:08:41,290 --> 00:08:38,719 comes out of solution the reason is that 211 00:08:42,760 --> 00:08:41,300 it forms beautiful beta structures right 212 00:08:44,890 --> 00:08:42,770 those aren't just random precipitates 213 00:08:47,140 --> 00:08:44,900 right those are those are assemblies 214 00:08:51,450 --> 00:08:47,150 that have been designed by Nature over 215 00:08:55,620 --> 00:08:51,460 long evolution how much time do I got oh 216 00:08:58,000 --> 00:08:55,630 okay good so we talked about proteins 217 00:09:00,370 --> 00:08:58,010 spontaneously folding right you take a 218 00:09:03,010 --> 00:09:00,380 protein in solution and it will 219 00:09:05,350 --> 00:09:03,020 spontaneously fold but the only reason 220 00:09:07,810 --> 00:09:05,360 for that is that you're cheating on the 221 00:09:09,760 --> 00:09:07,820 accounting if you really add everything 222 00:09:12,880 --> 00:09:09,770 up like how much did it cost to make the 223 00:09:14,769 --> 00:09:12,890 amino acids how much did you invest in 224 00:09:17,470 --> 00:09:14,779 selecting for the right sequence and 225 00:09:20,200 --> 00:09:17,480 then of course for making the bonds in 226 00:09:22,269 --> 00:09:20,210 an aqueous media proteins do not 227 00:09:23,920 --> 00:09:22,279 spontaneously fold right they only 228 00:09:27,670 --> 00:09:23,930 spontaneously fold is because you're 229 00:09:28,690 --> 00:09:27,680 starting with the polymer okay so and 230 00:09:33,070 --> 00:09:28,700 that's kind of cheating 231 00:09:34,560 --> 00:09:33,080 thermodynamically so this is I think the 232 00:09:37,300 --> 00:09:34,570 way to think about it 233 00:09:40,269 --> 00:09:37,310 this is what nature can do really easily 234 00:09:42,460 --> 00:09:40,279 and what nature has done is it has 235 00:09:44,829 --> 00:09:42,470 separated the cost of the assembly 236 00:09:47,260 --> 00:09:44,839 Nature wants complex assemblies it wants 237 00:09:51,010 --> 00:09:47,270 informational biopolymers it wants 238 00:09:53,949 --> 00:09:51,020 catalytic sites and it has separated the 239 00:09:56,769 --> 00:09:53,959 cost of that assembly from the making of 240 00:09:59,250 --> 00:09:56,779 the assembly so the sequence of this 241 00:10:02,050 --> 00:09:59,260 thing and the backbone has been designed 242 00:10:04,600 --> 00:10:02,060 by billions of years of evolution right 243 00:10:07,540 --> 00:10:04,610 that is an investment that Nature has 244 00:10:09,340 --> 00:10:07,550 made in this polymer it has selected the 245 00:10:10,750 --> 00:10:09,350 side chains it has selected the sequence 246 00:10:13,120 --> 00:10:10,760 and then what it actually does the 247 00:10:14,769 --> 00:10:13,130 polymerization of course it uses ATP and 248 00:10:16,900 --> 00:10:14,779 high-blood so there's an enormous amount 249 00:10:20,530 --> 00:10:16,910 of energy that is put and the reason 250 00:10:22,960 --> 00:10:20,540 that energy is invested is in order to 251 00:10:28,810 --> 00:10:22,970 make assemblies and so this is this is 252 00:10:30,250 --> 00:10:28,820 the analogy I use money if you don't 253 00:10:32,710 --> 00:10:30,260 have to pay for stuff you can have 254 00:10:36,010 --> 00:10:32,720 everything right and that's what Nature 255 00:10:39,610 --> 00:10:36,020 has done it has invested so much in the 256 00:10:40,930 --> 00:10:39,620 past that assemblies are free and so the 257 00:10:44,230 --> 00:10:40,940 way to think about it is if you have 258 00:10:46,420 --> 00:10:44,240 saved your whole life for your kid to go 259 00:10:47,710 --> 00:10:46,430 to college then you can send your 260 00:10:49,720 --> 00:10:47,720 college to your kid to college 261 00:10:51,880 --> 00:10:49,730 essentially free because you have that 262 00:10:53,160 --> 00:10:51,890 account and you're not you don't have to 263 00:10:55,900 --> 00:10:53,170 pay for it in real time 264 00:10:58,840 --> 00:10:55,910 that's what biology has done biology has 265 00:10:59,980 --> 00:10:58,850 been investing in in assemblies for 266 00:11:02,110 --> 00:10:59,990 billions of years 267 00:11:04,810 --> 00:11:02,120 and has made them spontaneous and it and 268 00:11:07,030 --> 00:11:04,820 free right this is why nature does such 269 00:11:09,130 --> 00:11:07,040 crazy things because it really doesn't 270 00:11:11,110 --> 00:11:09,140 have to pay for it right it's it's 271 00:11:13,600 --> 00:11:11,120 already paid that investment is a done 272 00:11:18,220 --> 00:11:13,610 deal and and everything it wants to do 273 00:11:23,530 --> 00:11:18,230 is essentially free so thank you guys 274 00:11:25,330 --> 00:11:23,540 this is my group and actually I have 275 00:11:27,700 --> 00:11:25,340 this is Moran who has done a lot of work 276 00:11:29,170 --> 00:11:27,710 on the DEP c-peptide stuff this is Anton 277 00:11:29,680 --> 00:11:29,180 who talks to me about these things all 278 00:11:31,240 --> 00:11:29,690 the time 279 00:11:39,520 --> 00:11:31,250 and the other member of my group are 280 00:11:41,260 --> 00:11:39,530 here thank you guys okay we can only do 281 00:11:43,660 --> 00:11:41,270 one quick one because I've been informed 282 00:11:46,900 --> 00:11:43,670 that we have another group coming in 283 00:11:48,700 --> 00:11:46,910 right after us okay so yeah usually 284 00:11:50,320 --> 00:11:48,710 disagree with Lawrence I hope you're 285 00:11:53,770 --> 00:11:50,330 going does he didn't say anything about 286 00:11:54,940 --> 00:11:53,780 human beings so it's I thought an 287 00:11:56,800 --> 00:11:54,950 interesting idea about the water 288 00:11:58,900 --> 00:11:56,810 activity being like the first metabolism 289 00:12:01,870 --> 00:11:58,910 when I talked to RNA world people they 290 00:12:04,210 --> 00:12:01,880 usually don't talk about metabolism in 291 00:12:06,970 --> 00:12:04,220 that world so you but you need some type 292 00:12:09,220 --> 00:12:06,980 of energy to replicate yourself so is 293 00:12:11,050 --> 00:12:09,230 that is water activity variation a 294 00:12:14,170 --> 00:12:11,060 candidate for the metabolism in an RNA 295 00:12:16,180 --> 00:12:14,180 world I would say no because RNA is so 296 00:12:18,580 --> 00:12:16,190 far from equilibrium that these 297 00:12:21,310 --> 00:12:18,590 processes in fact I would say RNA is a 298 00:12:23,200 --> 00:12:21,320 very derived polymer that comes from a 299 00:12:25,000 --> 00:12:23,210 lot of chemical evolution or if you look 300 00:12:25,720 --> 00:12:25,010 at peptides and sugars and other things 301 00:12:27,160 --> 00:12:25,730 you polymerize 302 00:12:29,410 --> 00:12:27,170 you can do them near equilibrium by 303 00:12:31,150 --> 00:12:29,420 dehydration it's very simple RNA because 304 00:12:32,770 --> 00:12:31,160 it's so far from equilibrium with that 305 00:12:34,930 --> 00:12:32,780 phosphate that's the only polymer that 306 00:12:36,460 --> 00:12:34,940 it doesn't work so I would I would argue 307 00:12:38,470 --> 00:12:36,470 based on that and some other things that 308 00:12:40,240 --> 00:12:38,480 already has a very derived polymer and 309 00:12:42,400 --> 00:12:40,250 it of the polymers we have it's the one 310 00:12:46,330 --> 00:12:42,410 that is farthest away from the sort of 311 00:12:49,129 --> 00:12:46,340 origins of chemical evolution alright