Assistente AI
Trascrizione
00:00:11I contenuti dei topic
00:00:16and giusto the mind and communication actually just to.
00:00:24Do it so that I can you to the student sheet.
00:00:30Okay, so.
00:00:48So. So. Uhm, identica to the last time, except last.
00:00:59Adesso per molti di quelli di.
00:01:07AM so if you take notes on
00:01:11the slide download them again so last time.
00:01:16We started to di the problem of prediction di identici what is
00:01:23di information about this what is what is information and?
00:01:32Essential there are concept is
00:01:37the information is what so it's defined configuration
00:01:43so starting from the sequence always only one possible solution
00:01:48that is the codec solution with looking for and that
00:01:53di energy of the molecular so the Combination
00:01:57of interaction core energy that's possible for
00:02:03specific configuration some exception is that
00:02:09functional configuration natural configuration for I configuration
00:02:18is the functional that the conditions which proteins can
00:02:23adapt functional configuration and
00:02:27they were they often corrisponde to.
00:02:31Specific patologi is so with defined problems,
00:02:35so what is the function that it was di coordinate
00:02:42single atom belong to
00:02:45this sequence of assets in the three dimensional space.
00:02:50This is again just representation,
00:02:53you are not looking at the atom surface is not the position
00:02:58of the alpha carbon so the carbon tax,
00:03:04so this is presentation that is the place of carbon and
00:03:09how they are connected and
00:03:11organized space so the problem of folding.
00:03:15This is an example again so it's about finding a sequence of moves,
00:03:25that's from palline da objectives e
00:03:29a final cut solution is not the same proteins is a difference,
00:03:36especially we see the unique set
00:03:41of moves that is the final solution,
00:03:45many and also we this about so that
00:03:53proteins spot sta dando
00:03:57luogo a long all possible moves and all possible solution
00:04:03you get the proteins in
00:04:06reasonable time so if you think about six possible information
00:04:11for one and long so meaning that
00:04:14every could make six different moves and you test of them.
00:04:21This is the amount of a moves
00:04:24that you should trust and this is about time that would
00:04:28like to sample consider
00:04:30a second for every single moves so this is in
00:04:36the observer experiment where proteins
00:04:39actually fall in less than one second so
00:04:44this time to one second something
00:04:48that should explain with paradox is not Eh?
00:04:55So what is we started looking at local information of proteins.
00:04:59This is something need to introduce to each and talking about
00:05:05we so that proteins are organized in Alfa Ellis and vita sheets.
00:05:13There is difference between the two in the name
00:05:17actually indicate is that difference about so here.
00:05:22We are not for this is that actually dropdown,
00:05:27which is online di orientation of the Alex Orbit sheets.
00:05:34You have this elements representatives
00:05:37about also hear this is yet another presentation
00:05:42of their still many looking at
00:05:46the connection between alfa carbon, but the Felici.
00:05:51Sheets you see. So you are you you
00:05:56see what is this is in the other configuration,
00:06:01you may not where is it is not really
00:06:04liked and this is that the presentation and you see the bit a bit.
00:06:11IT is actually a combination of
00:06:14multiple bits streams so every of this is the strand.
00:06:25Context. Is one of
00:06:30DNA molecole one is strand combination of these are you and.
00:06:38So what is an about this second factors part and how they are.
00:06:47You see that.
00:06:51You have a specific pattern of bonds that especially for analysis,
00:06:59especially for alpha analysis.
00:07:02You have one survey for so this nitrogen year of
00:07:12change is connected with the oxygen bond with the oxygen
00:07:20of time and that is
00:07:23the way and this is specific type of course, of course.
00:07:30We observer sperimentali that is
00:07:35one those that are either bonds or those that it is.
00:07:43The way less stable,
00:07:46of course the shape and the.
00:07:48the side of the change a little bit.
00:07:52And. The last but not for the state,
00:07:59of course for you also have
00:08:04bonding and that the structure and you see in in this case,
00:08:10you don't have actually and that you you and after
00:08:16even number of this is that they can form
00:08:19bound between far away in sequence.
00:08:23You have to type of the types of
00:08:27sheets until parallel and parallel sheets and
00:08:34parameters you can be
00:08:40because you actually know what is the direction of
00:08:45the Constraint instance this one goes from end to end as
00:08:51this orientation and other one does di
00:08:55the other way so there is difference,
00:08:59this one is more stable.
00:09:01This is an orientation of the is more linear year.
00:09:08They are and also in proteins you
00:09:13can have most of proteins sheets and
00:09:18sheets sheets or just two streams for usually
00:09:25you you see at least four five streams
00:09:30always structure is not stable.
00:09:32So much more frequent to see this structures.
00:09:39Okay, we started about the degree of
00:09:43freedom of protein And this is also useful to this
00:09:46about energetic consideration system am
00:09:52again year you have the man in
00:09:55the night of a carbon and carbon carbon plastic,
00:09:59oxygen and di bond e
00:10:02actually year you you know how to the molecular and other authors
00:10:09can take am in the other
00:10:13molecular and you have to make am english for the main chain.
00:10:19They are you see you can create angels consider the planes.
00:10:26Previous for the di the upstream
00:10:29for life and the downstream for slides
00:10:33because this for our aim fix on the planet year.
00:10:40You don't see you from this is that you have a Double bond
00:10:43So this for atom are not their fixed,
00:10:47but they can of the year and so on the alpha carbon.
00:10:51You have this to bonds that are single bonds and.
00:10:55Of course this is to also for
00:10:58the side chains so there is one man of
00:11:01freedom that is KEE year except
00:11:06of force for were falling
00:11:09as is a cicliche acid and its connected with the main science of
00:11:15its it also block think one of the single so
00:11:22for the other side of free to
00:11:26move that the impact
00:11:30on the overall structure of the movement of side,
00:11:33of course is less critical to the fine side.
00:11:38If you think about that it is
00:11:41just a sequence of one of the other if you make a move year.
00:11:46You are actually the configuration
00:11:49of the rest of the model for all di.
00:11:54After the.
00:11:58Change so this is just presentation of the two planes.
00:12:05I was talking about before and by side
00:12:09where where they are and how they can effect the structure,
00:12:14of course this is a way to look at the structure network.
00:12:19Los angeles course cares about energy,
00:12:23but this is very interesting because you can
00:12:27compare proteins or analysis analyse proteins blotting.
00:12:31This is the combination of this is for every of
00:12:35carbon is to this two di presentation
00:12:39where you have by side on
00:12:42the plot and what you know when you analyse TALAPRO-2 with
00:12:48the state of presentation is that most of assets lines
00:12:54in specific areas corrispondente to
00:12:56specific what is it mean it means that.
00:13:04IT means that time for instance elites are
00:13:09always form by a minoranze always on the specific.
00:13:16Of Annals of management and you can not actually aim
00:13:23and that is form by combination of a different orientation.
00:13:29So you can find
00:13:30sort of the current patterns of
00:13:33the current angle and probability of
00:13:36observer Values of angle in specific vision of this plot.
00:13:45What you can also notice is that for some aminoacidi,
00:13:49you have outliers and often this outliers to
00:13:54functional reasons of this players here for instance.
00:13:58They are aim in the middle of
00:14:02this protein and information that is very flavor is
00:14:08highly energetic so it's like they are trigger to be ready to
00:14:15change information when we the day have
00:14:19to to modify order questions of war,
00:14:24we just di degree of freedom proteins
00:14:28di dogs and another way to the present proteins to Film.
00:14:39Su The other we look at least time is
00:14:44the third party is about the energy so there is one of the energy,
00:14:49so right to explain,
00:14:51why protein is stable and configuration is not
00:14:57a spaghetti live structure
00:15:00and and other thing is about the process of holding.
00:15:06So the planet of the process and its fast and doesn't
00:15:11take off the years and this is this actually applied to all.
00:15:17He he reactions.
00:15:20So what is.
00:15:23The space we about the chemistry.
00:15:30It's used to this and about the energy of the system and the.
00:15:34news describe states functions describe
00:15:40the state of system without saying how is that state
00:15:45is that useful because this you about am
00:15:51a reaction news and if
00:15:56action is it doesn't mean it will have been in this amount of time.
00:16:01IT just means that is not totally
00:16:04caring and even it can be super energetic.
00:16:09IT doesn't mean it I will happen and you can also tell you about
00:16:14something about if the system is at the equilibrium
00:16:18or not and of course of energy,
00:16:22which is the for.
00:16:27Example of functions are pressure temperature Consentire.
00:16:35We have to define what is a system?
00:16:38What is an what is a showdown?
00:16:41And you can have different type of systems.
00:16:44We can have open close.
00:16:48And isolate system where the can exchange energy matter what.
00:17:01And we started to introduce to this one is what is called
00:17:08internal energy and essential you measure and the end of process.
00:17:15So you can easily what is the end of
00:17:19the process just looking at what is the exchange of
00:17:23it in the process so you just between
00:17:29the final state to
00:17:31chiudi Initial state and internal Previous slide
00:17:35The first slide is a state function.
00:17:41Of course. This is a special case and
00:17:46this supplies very well in the context of chemical reactions,
00:17:50where we are the pressure is constant,
00:17:54of course it's different when you with
00:17:57different use of systems like classes or of things
00:18:01that really this is just about
00:18:04the exchange of it so you have to situations,
00:18:09of course you can have and reactions so you are reactions
00:18:14your system your system think about your molecular transformation.
00:18:21Reactions your molecular and you will be it from the sounding.
00:18:31Reaction so.
00:18:34Reaction is using health and think about compassion actually
00:18:41making know how with oxygen the product is carbon oxide.
00:18:47Plus keep it can be considered as a product or
00:18:51reactions actually be button reaction to
00:18:55to balance so and that is the end of compassion year di design of
00:19:05di in this case is negative
00:19:09for migration and you can have the formation
00:19:13so di case in which you are
00:19:17more interaction and so it
00:19:20is so every time you form a new interaction,
00:19:24a chemical bond is like you are.
00:19:28Accumulate in energy so making bond as
00:19:33a cost at the slide that you want what is the end
00:19:38of bond exactly energy that by the process to form
00:19:46this chemical bonds can be ADCs effect do not ebraica he operation.
00:19:57And we introduce another and other concept
00:20:01that you have seen in other contest.
00:20:05This entropy entropia simply measure what is.
00:20:12The energy so is not something that is exchange as
00:20:16it is that measure of the number of micro states.
00:20:21Simple can am adopt so,
00:20:26of course air entropy means that system can be more makes
00:20:31states loved and means that lower number of micro states,
00:20:38of course and is a function am to the temperature so if
00:20:48you is the system of using the number
00:20:53of a di of the system in via di think about water.
00:21:00When you is for the end of this is lower to the end of water,
00:21:08many more states so all things and of course it.
00:21:17Is not that's connected to the second long term dynamics and
00:21:21I the last something about nato da transformation They
00:21:25are considered they are black
00:21:28and so everything that actually increase
00:21:32di total entropy is a spontaneo reaction to.
00:21:41Dynamic our universe things to increase di di Entropy.
00:21:48IT is not the end of our process
00:21:54negative di process is and not
00:21:58continuous if total entropia is zero.
00:22:01IT is that we are equilibrium so this is sort of the beginning.
00:22:10We also play a little bit about
00:22:14this exercise and we finish years so I think last time.
00:22:19There was a mistake here it was in A insultarmi o endotermico
00:22:24Was so just is my mistake so.
00:22:32Can you explain again.
00:22:34Why the Last example is now.
00:22:38Because the number of molecular they are so you are you have
00:22:42molecular acting with molecular.
00:22:49And you are actually form to
00:22:52molecular di asset so essential the number of molecular is
00:22:57same so you are not you can not say that
00:23:01the configuration of the system
00:23:05is different from this one because the number of this is the same,
00:23:08we have one one and to the problem
00:23:13is what are the space that this to
00:23:18modules individuali cannot be to
00:23:21the Marco e sia Willy at this level should look at the aim.
00:23:28Electronic distribution of how they flood so
00:23:32it's difficult to to evaluate since.
00:23:39As well as he was the seventh group so it needs one to.
00:23:52The stability is about the number of configuration so stability is
00:23:59about admin how it's more related to the stability because this.
00:24:08Is reactions. There is now a connection stability
00:24:14of this is just about so to the stability
00:24:19ITS whether this actions the speed
00:24:24of this reaction so di the mayor doesn't that you
00:24:29anything about what is the aim
00:24:33di equilibrium of this reaction what concentration feeling
00:24:39al puls equilibrium That's
00:24:43probably that's it to the stability and internal configuration
00:24:49of the bones between elements and we will see that in
00:24:54a start talking about the end of the actions,
00:25:00but in terms of entropy is very difficult to
00:25:04do it's not non because this is are different,
00:25:10but it is very close to
00:25:12see so there is not much difference and is not something
00:25:15you can just looking for
00:25:17the Actions here is more because of the times.
00:25:23We are more molecular or and indeed if the number
00:25:30of this is changing when you. Are not.
00:25:39So the entropy is is not about stability.
00:25:46No is not di energy of the bones is about
00:25:50the number of configuration of the system weather in the reaction.
00:25:54IT is increase or it has decrease.
00:25:57Because that is the energy so I thought that
00:26:04if and combined configuration that is
00:26:11less energy then di entropy di cose.
00:26:19Di Entropy This is
00:26:24this is it because is not the energy is this number
00:26:29of this is the energy that you can not measure as it or
00:26:33as is the energy is the contribution of the energy of the system,
00:26:39that's di energy, that's not as it.
00:26:48Is. But think about this is the number of sales,
00:26:57that's make science and that will explain within at the end.
00:27:03To if they have if they are both in
00:27:05the same state and the number of this is the same.
00:27:10Then you may Deming.
00:27:14gas. Serra di status System configuration.
00:27:27Energy accounts for both things
00:27:31so it can actually tell you something
00:27:33about something more about your reaction and especially it all us.
00:27:38If its spontaneo reaction to you have.
00:27:43You you know if reaction or and other on weather accumulate,
00:27:51please heat on the surround and
00:27:56combined with the change in entropy you can also
00:28:01know if the action or
00:28:04not so all spontaneo reactions are ADCs effect and you see.
00:28:13here when you have an reaction and di.
00:28:20Andy. Ehm. Ehm. Difference in.
00:28:28Inglese Do you do you have?
00:28:33You think about an example of such a reaction.
00:28:51Okay. Combustione. Spontanea di ossigeno in.
00:29:01The number of.
00:29:06Entropy usually increase because usually A model of carbon
00:29:13made of many carbon on the same molecular and during the molecular.
00:29:20So you have more molecular foundations so also
00:29:24di ECM di Enzo in crisis and
00:29:29containers so question its reaction
00:29:34we are made of carbon why we are not burning that now.
00:29:40Because this is the actions actually we are
00:29:44burning that spontaneo reaction it doesn't mean that is fast.
00:29:49This is simply tells you that the è spontaneo so
00:29:54if you have it will or if you hit the system a little bit.
00:30:00Maybe you can trigger see what are the molecular exploration why
00:30:06spontaneo Actually means that reactions occorre to the other cases,
00:30:15when the first of all you see the formula you have.
00:30:21Minus this temperature multiply by the entropy.
00:30:29You have another case you have an reaction
00:30:33again something that is it,
00:30:37but the entropy for
00:30:38some this decrease you
00:30:41are not for instance di the amount of modules
00:30:45that are not the sign of the energy can
00:30:49be both negative o positive it on the temperature.
00:30:54So if the contribution of temperature is not to
00:30:57balance the changing of course
00:31:02it becomes am not any more spontanee so
00:31:08a new year when this is smile.
00:31:16You have a lessons and to cases are
00:31:21the reason is is the same so why? Yes.
00:31:29We can. In realtà.
00:31:43We are not burning because this is the last,
00:31:47but not force, but actually in inside out.
00:31:53There are processes where oxygen situation or of course is
00:31:59super control and that take off this Is to have to read creating,
00:32:09but indeed, if you think about with
00:32:12carbon carbon and we breathe oxygen and we
00:32:18produced carbon oxide so if you think about
00:32:21the product reaction is actually a combustione produce energy,
00:32:27of course, di trick for our body is not to eat,
00:32:32so di the product of nations is not in our case,
00:32:37but not which is energetic.
00:32:42And indeed our system we evolve to develop am a system
00:32:49or a pathway of actions that actually can
00:32:53transform combination in the new energetic modules.
00:32:58So why we were talking about
00:33:02this things because we want to think about proteins
00:33:06so see what we describe here we are funded so the fact that the
00:33:14folding process process after explain why process is fast so.
00:33:23We can think about folding as
00:33:27a chemical reactions so we can have am he leggi of folding
00:33:34is actually the difference between
00:33:37the old state and the native configuration and measure what is
00:33:42this experiment is what we can find
00:33:45sperimentali is that the overall energy of protein,
00:33:50including the system so including the end of the solvente
00:33:55so against the system
00:33:58is not the protein isolation without anything,
00:34:01but is the protein with water protein with water is
00:34:05a system measure energy protein think about
00:34:10protein plus solver and that
00:34:13the only way you can make science of water.
00:34:17So if you measure default and process of
00:34:20protein is spontaneo reactions.
00:34:24Our energy is close to zero so think
00:34:29about the member energy single bond is
00:34:34about the local essentials protein
00:34:39is its folder because of a novel to one two,
00:34:47but that is for instance.
00:34:52So am.
00:34:55I don't understand why it's so low.
00:34:59Slides And its soft law and indeed,
00:35:06what happens that if you with
00:35:08the temperature bit you can actually break the folding protein.
00:35:14Think about when you cook for you make
00:35:17it when you go to become solid because actually you are the things,
00:35:23they becomes linear and they
00:35:26can start up on top of the other so they become some more
00:35:30than to instead of having spears you will start dating lines that.
00:35:39IT on top of the other and that's it.
00:35:44Process that's happening all the times that you can all
00:35:47the time to you also for instance when you.
00:35:53Do it in English you do
00:35:56permanente on your Io voglio Keep it dem you are
00:36:02actually breaking hydrogen bonds hydrogen bonds are
00:36:05making years are you can also use
00:36:08chemical agents longer dei
00:36:11brake sul file system connections o bonds.
00:36:17So and process have are made
00:36:22proteins so connection so their marginal stable.
00:36:29Despite i look at what are the contributions di the energy,
00:36:37of course is the combination of health and again.
00:36:43So you have a positive contribution of the enterprise that you
00:36:48see the sign is negative because it is an endotermico reactions.
00:36:52We are from the new interaction in bones.
00:36:58Introduction to everything is
00:37:02new interaction so the process is actually accumulate in energy,
00:37:09but of course we have a big penalty given by
00:37:14di loss venduti su the system is move one its.
00:37:22LINEAR for and of course when
00:37:26you need to the group of freedom is very close to zero
00:37:30is not able to move and more and so we have
00:37:34a big sampling in entropy from the golden state.
00:37:41If you look at this diagram is in
00:37:44scale so essential di the Lost Entropy is
00:37:48larger than the game
00:37:51of energy provided by the formation of new actions.
00:37:56So the must be something else so we need a little bit more.
00:38:03AM. AM a contribution of
00:38:08something the other contribution is
00:38:11the contribution of the soul and so.
00:38:15The soul is the water
00:38:18molecular and the proteins actually undergoing
00:38:22a change in the entrambi change in the number of configuration.
00:38:28So what is very special again.
00:38:32Water air force because liquid is not
00:38:38gas in this theological conditions or our body.
00:38:43Temperature, of course, and so it happens a weird fact,
00:38:47which is cold idrofobiche that we actually the entropy of the.
00:38:53AM the soul is.
00:38:58What is that is this situation here so think about
00:39:03the time is it the big model.
00:39:08So am this is very simple example is
00:39:14not even think about it is a sides time
00:39:19or molecular of a fat where you just it carbon and its well water
00:39:26to to stay at the like this forms a cake like this one.
00:39:33So it increase is the number of.
00:39:36IT decrease the degree of freedom so it is the orient is specific
00:39:43around the other so you are
00:39:47reduce the degree of freedom of
00:39:49water so down in the state of modules.
00:39:52So when you you for the protein actually you
00:39:57are exclusion those reasons idrofobi reasons think
00:40:02about your mind inside the spear
00:40:06and so you are using the surface or the amount of exposed for
00:40:12change the public size to
00:40:14the water servant and you are reduce the amount of
00:40:18water modules that are in
00:40:20a fixed configuration may be this is more clear and the next slide.
00:40:25So you see the number of cases or fact that we have to
00:40:29form a cage for every single minor asset and
00:40:33when you combined them you see some of the water molecular
00:40:38are not Nesli am am in
00:40:44contact and more with the public positions modules and
00:40:48even year when you form a you were on
00:40:53the surface you have the polar or interact in
00:40:59water and you see you including al piano di sopra.
00:41:07This is the contributions that balance di the loss of of
00:41:14the also the question time to your league who is so not so stable
00:41:24despite for the lot of actions
00:41:26actually the combination of
00:41:28the interaction internal connections to have
00:41:30as so it's actually for lot of internal connections,
00:41:38but there is the loss of
00:41:41it's really the main factor that actually would prevent in
00:41:47normal conditions without water to protein
00:41:50holding to the place of fundamental role in
00:41:54the folding and balance
00:41:58of the system and without water of course never fold,
00:42:03we explain year with termodinamiche while tennis
00:42:09stable that protein says this is stable,
00:42:16but marginal stable so it's really easy to make
00:42:20the folding some how we know what
00:42:25has been found as logical exploration while proteins can
00:42:30folding in in seconds or cycles other questions.
00:42:38Yes different.
00:42:41Soltanto nei.
00:42:44Piani superiori,
00:42:46ma also hiding Champion's solution
00:42:50cannot make the time is over structures,
00:42:54you can also see proteins that the way when
00:42:58you should you see the folding and other way and
00:43:02some proteins are designed to switch
00:43:04information on the conditions for instance protein inside
00:43:08a cell and then it export side
00:43:12where the conditions like the different you can see information.
00:43:26And the rules that the Nike free ADCs effect.
00:43:36There are some proteins that foods,
00:43:42this is for most of proteins.
00:43:45So you can eat And.
00:43:49Conditions like when you so you don't only break folding,
00:43:55but also break the things to you you have
00:43:59it also some of the rules the chemical bonds.
00:44:05There are cases where proteins are not folding directly in the
00:44:11final confirmation da helper proteins their chaperon.
00:44:17That's sometimes then brake for instance.
00:44:19This is it that is not protect
00:44:23food and so you have a second chance to form folding.
00:44:27So dei dei, dei, dei, dei proteins,
00:44:30dei file bonds and dei leaf protein,
00:44:36folding and society of course,
00:44:39which is functions of.
00:44:43The Tende con forza all questions.
00:44:49Some said that it is back to water has
00:44:55less freedom because it has to say this is.
00:45:03That is the game of the soul,
00:45:08but we have less is.
00:45:11More because of think about think about
00:45:14the fold structure as a combination of this models of
00:45:20course year you have single molecular think about they are
00:45:23connected like it is connected with this one think about this.
00:45:28This is the main change actually are you
00:45:31have three cases so the amount of order of
00:45:34this is more to this one where the number of us that is to form,
00:45:41this organized KEE is and even less.
00:45:45If you forma so the exposed surface
00:45:50from a linear object object of course
00:45:55that surface is not idrofobico is less is
00:46:01just the number of water rules that
00:46:04are in contact with idrofobiche.
00:46:07So so science and think about this is these are the size changes.
00:46:14Yellow means idrofobiche means.
00:46:26He di entropy gain it means that water that are not
00:46:32directly encounter with the surface of protein
00:46:35are free to move at the day.
00:46:38They move more compared to the modules that are here if they
00:46:42are here they need to say no configuration.
00:46:50States that we are.
00:46:54Microsoft means move. System.
00:47:10Discovery has been found years ago.
00:47:19Okay, so am just an example of
00:47:23a albumin albumin is also
00:47:26a special case because albumin is designed
00:47:29to to a number of us in our blood stream
00:47:34so it contains a lot of
00:47:38idrofobiche based on the surface to this is a special place,
00:47:42which I think thank you have to see their many on the surface,
00:47:50they're many on the surface.
00:47:52Most of things that are soluble they are that mini.
00:47:58Service folding patterns exploitation.
00:48:04Actions like folding.
00:48:09So what about the dynamics so we reason about.
00:48:17If reaction is containers or not an negative.
00:48:24Reaction. So if you think about
00:48:29the energy action think about this is the initial manage.
00:48:34This is the final energy of
00:48:36the products data diagnosi
00:48:40is negative so this is containers reactions,
00:48:43but it doesn't anything about the end di speed to the speed
00:48:48actually the pants on the intermediate states of the reaction.
00:48:55So this is my actions.
00:48:58So in this case you see you have this is
00:49:01that it is the final States to this case you see.
00:49:06This is this oxygen is transfer
00:49:10to this year you have to this what is the transition state
00:49:16where where all the atom are connected to each other da
00:49:23very short time and
00:49:26also the transition States higher energy to you.
00:49:31This is an energy,
00:49:33of course its process do
00:49:37this configuration means that you have to this time to collide
00:49:43with the energy with the half speed
00:49:46actually and they have also to collide
00:49:49in correct orientation so
00:49:52if you want to transfer oxygen to the carbon,
00:49:56this is this carbon and
00:49:59not this oxygen so if I think about that in this is
00:50:05the temperature increase di energy of
00:50:08the increase di possibility of making
00:50:14a. Collision so that's
00:50:20the vision temperature place in speed up to process so
00:50:25when you you are
00:50:28you and you increase the possibility matchmaking good conditions
00:50:35and you actually increase the possibility of being
00:50:39this transitions with the transition state of
00:50:45course this direction actions and if this is lower
00:50:51and its more likely that you go this actually this is actually,
00:50:57this is not to you can do ways that you
00:51:01are here you see to actually get back to the transition,
00:51:06stay state takes more energy so it's less likely
00:51:11that you transition states state peer to peer.
00:51:20Engines actually works on on this concept and
00:51:28actually the crisis di energy of transition states
00:51:34because this place the state in position or in the city.
00:51:39This is for instance in close and I can quickly place.
00:51:48To. So. Spontaneo reaction
00:51:56can by the slowly if the activation is to.
00:52:04This transition state that's on the way.
00:52:10Jules interrupt and if they have enough energy, of course.
00:52:18You have to break this bound and form another
00:52:22bound here so you need to sort of transfer.
00:52:30Energy is the one from
00:52:34the beginning to the transition
00:52:36from the end to the transition or both.
00:52:39You have actually two different activation one this is one and.
00:52:46Energy, that's the activation
00:52:51and you have the energy of the transition States,
00:52:54which is actually results
00:52:56some of the activation plus energy of the.
00:53:01Products so the city.
00:53:06Is the mind by the power of energy di the temperature, of course,
00:53:16and he activation I'm not supporting all the types of the actions,
00:53:23but actually measuring the speed or the date at
00:53:29the product form to
00:53:32be the change of concentration of di the agents.
00:53:36You can actually determined type of the actions
00:53:40how many conditions states are the and
00:53:44that out of the out, of course.
00:53:49Ehm, okay, so what happens for proteins,
00:53:55so and other consideration.
00:53:57Sorry is the type of the year.
00:54:01See you later so on the way,
00:54:05always have the energy to education and energy on the axis
00:54:10or the axis usually its presented di coordinate di reaction so.
00:54:18In this case we have for nations breathing of bones for proteins,
00:54:25of course that they are formation as kings
00:54:28of interaction they are not chemical bands,
00:54:32but think about di this dimension here or to dimensions in corso.
00:54:39Two dimensions presents the different configuration different
00:54:43shapes different combination of interaction or for a specific.
00:54:50Configuration so presentation like this is the energy and one two
00:55:01are just coordinate you can not present
00:55:04energy with dimensional coordinate that is just indicate
00:55:08that every point in
00:55:10this three dimensional space present a configuration of
00:55:13protein specific and specific energy so
00:55:18the paradox shows something like this what
00:55:22we have number of configuration similar
00:55:26to something that is not for an equal energy
00:55:30so sampling a flat surface so.
00:55:36All this configuration the surface are
00:55:40the air or I so folding or fold proteins.
00:55:46Jumping one. And then
00:55:50once single configuration the one which is at the lower energy
00:55:56and this is the paradox so you have
00:55:59proteins that sample of possible configuration and
00:56:03certain point a very new year in the energy energy landscape
00:56:10very path to the configuration
00:56:15so it's like this is just one specific set of
00:56:19moves over very large settled moves that lead to di nati morti.
00:56:27Solution. To some options
00:56:34approach all possible information
00:56:37here information of this independent of the last,
00:56:42but not only to see.
00:56:48A video year.
00:56:54Simulation of art and other hypothesis is that along this.
00:57:05Last surface was last golf landscape
00:57:11another option purpose proposal was there was
00:57:16a year as like for chemical reactions where you have
00:57:19specific intermediate states and we have to follow
00:57:22this pacific To the two to get to the configuration.
00:57:29That is a problem for proteins
00:57:32because having force which think about
00:57:34the formation a single and balance of interaction is breaking it.
00:57:42Easy it can be just the result of
00:57:47random change in configuration and
00:57:53its many form by driven by
00:57:58the interaction so really it doesn't explain why
00:58:03di protein folding so di
00:58:08the fact that is good by interaction the means that
00:58:13the day for protein to the final state is
00:58:19always possible so it's not true that there
00:58:23is a place where the protein can just fold pattern.
00:58:29Something that should happen every starting positions of protein
00:58:35so their something different is
00:58:37the final solution is that the energy landscape.
00:58:42Is something like this where you have a final shape and essential.
00:58:51What is that starting
00:58:55any point any possible configuration every move that you do
00:59:01for a new interaction is actually the using
00:59:05the energy and is actually leading within the process towards the.
00:59:14Dexter basin explain why that the nation is that
00:59:20proteins not just designed to go to adopt information.
00:59:26They are designed to fold in a time meaning
00:59:30that they farm a new interaction that
00:59:34interaction is actually you can consider
00:59:37it has native interaction so di energy of
00:59:40the system is going towards natives structure.
00:59:49So the probability of going to the United States.
00:59:56So the bottom is very high.
01:00:04So actual the real case for proteins
01:00:09is a dag panel is more realistic in which you see
01:00:15you have the beginning in which Immediately from
01:00:19any possible untold Staten Island States you jump into something
01:00:25that humble state that you could have a number of
01:00:29local minimum so number
01:00:34of intermediate information that are not the minimum,
01:00:38but can be simple and where you can do you can
01:00:44jump towards the minimum and this is
01:00:47actually what is this is actually the world.
01:00:50We so before the questions of your league.
01:00:54Let it to the facts that we can fall of food and said on the same.
01:01:04Information after being.
01:01:10There is one other concepts concept
01:01:14of this is connected, of course.
01:01:18so proteins are not random is the sequence.
01:01:23Satispay old school the principal station to their
01:01:27selected of course does billion of years to to
01:01:32select these consequences and
01:01:36scoring function is not to have just a stable structured,
01:01:42but to each the stable configuration.
01:01:45In this time.
01:01:48So again this is the final this is the future.
01:01:56This is the di the situation here what you see is more than it's
01:02:04a state protein sample the final structures this is that the
01:02:09last that needs to be defined configuration is to be a. Ok,
01:02:17so minimal illustration concept,
01:02:21natural minimal conflicts most introduction to the same goal.
01:02:29Of the panel that is what is this is for stations,
01:02:36they are not perfect smooth.
01:02:41Was explain before and its also connected that the
01:02:46last station so this local.
01:02:51Minima sometimes are functional so sometimes
01:02:55proteins switch between two configuration
01:03:00where they need to a perform different functions on
01:03:03the configuration that they are adapt and this
01:03:08is the summary of explain before and
01:03:12questions So this is the United States,
01:03:16so this is the healthy.
01:03:19And landscape for hate speech to see you
01:03:27can have cases in which is
01:03:30the protein goes in the wrong, he configuration.
01:03:36Is not that law and does
01:03:40proteins called that actually break this structure and
01:03:45the print di the configuration and so on
01:03:48the other chance too big to fail to to follow
01:03:54the pathway and you have other cases where
01:03:58for happens don't work or the state
01:04:04in which you can form what are call a MorphOS or
01:04:09even work situation in which you So
01:04:14di which a configuration which you see it's almost linear and
01:04:21then multiple copy of the same proteins can
01:04:24start on top of the other and the case of Alzheimer.
01:04:29For instance they can grow slowly until they break
01:04:32di the brain of di neural science and you development.
01:04:39And sometimes this process is very slow time years.
01:04:46Questions. So the way it falls in seconds is
01:04:57because nature natural actions did not select
01:05:01only the configuration but selected the landscape
01:05:07with selected that every New interaction local level
01:05:13with your mind is actually moving the energy of the system towards.
01:05:22End, of course this is.
01:05:33This is not to do at the beginning so this
01:05:37is this point here you have configuration of
01:05:42things that are all that you start something that is
01:05:47actually am a new interaction stores configuration immediately.
01:05:54Diagnosi will drop an number of new interaction form and.
01:05:59I want to you the simulation of.
01:06:21Questo Smart.
01:06:23City. Presentation site changes form.
01:06:33Immediati non for some options that are highlights has fears here.
01:06:49Se is not the configuration you see that the first form.
01:06:57Inside number of configuration configuration
01:07:02is that is simple before.
01:07:05The final final.
01:07:24Final final si muove actually something
01:07:30moving year to actually change complete the structure of the.
01:07:38Final final Relations.
01:07:42This simulation think was the beginning is Microsoft.
01:07:53To its long if you think about one starting can be on.
01:08:02The road Tu tu simulate
01:08:06The folding is not something that's possible in with.
01:08:11Standard computer amount of
01:08:15time especially for large large process.
01:08:19Ma molto pathos.
01:08:26Okay, sono andato al question time think that's the last slide.
01:08:33AM you think about
01:08:38different ways proteins good folding process,
01:08:44especially for what the gods di intermediate States.
01:08:48You can think about that
01:08:50first second picture elements are
01:08:52form you can think about the first that is
01:08:56the eye of meaning
01:08:58that it first what you from the event Or you can think about
01:09:06this there's a few positions that are
01:09:09always mission interacting for sort of
01:09:13nuclear regions and from the rest of the stars.
01:09:20So this is the assembly year
01:09:25is means that you for the year and then you have.
01:09:32And on the second on the first options you
01:09:36di second stars form and then you need to assemble.
01:09:43Difficult to say what is the actual process from the simulation,
01:09:49you can not take the simulation as actually
01:09:52the examples so real time and
01:09:57Asti for our cases for sure alpha is
01:10:02are something that is the combination of the.
01:10:10Other questions.
01:10:13Yes. Bottom. Line creations means that we have
01:10:21just a few pool of contacts
01:10:25and thanks to that because you are also other resources
01:10:30nei form because and you always have the same initial contacts and
01:10:38only after those are you can from the rest
01:10:42of this is actually true for specific class of things.
01:10:46You an example year old proteins
01:10:51where you have things they are organizing
01:10:53modules and usually that's
01:10:56always some modules that is first and then to Intenso.
01:11:03Continuo di forex.
01:11:09Options to get out of this local minimum.
01:11:15By example external or something
01:11:19if you it up the system your breaking the little bit di di,
01:11:24di di also and ipotesi about
01:11:28why we the developed use of so actually
01:11:34increase a body and the idea is
01:11:37that you are of course acting our proteins by or also at
01:11:41the protein patterns so the hope is to take or make
01:11:48the more exposed to
01:11:51our new system for instance that is controversa.
01:12:02Or you can change
01:12:06the meaning or solution
01:12:10that of course change also static potential of software.
01:12:15Operations. Okay, so I
01:12:21don't have others slides about di The concept I hope that is
01:12:26that was clear the new set of
01:12:30slides is about present what are the resources
01:12:37that contains information about structures
01:12:40and also slide that where to explain are
01:12:46you can get information
01:12:48about the coordinate of protein so what are di
01:12:51experiment techniques that you can used
01:12:53to get the coordinate of the atom.
01:12:56That's not it's interesting,
01:12:58it's not that simple so to seconds.
01:13:28Okay, so.
01:13:33It's interesting story because this.
01:13:39Was really a big.
01:13:45Navigator from the community to make
01:13:49natural data open source for the beginning so is one of
01:13:54the Big Sacks in biology to make information and coordinate of
01:14:02logical modules available for everyone for free and thanks to
01:14:07data for the world or not
01:14:13to that and that that is possible to build an able to
01:14:20product structures in accurate so what you can do with your data.
01:14:28Coordinate e coordinate Spazio prediction see various levels of.
01:14:39What you can actually tackle
01:14:41problem structural competition and evaluation classification.
01:14:46This is also very important because give us ideas about what is
01:14:52the That we have
01:14:55year old many different projects
01:14:58so many different shapes and also very helpful.
01:15:00If you want to design your proteins.
01:15:04Prediction of protein interaction assembly force
01:15:08If you have to structures one to do is
01:15:12to see the interaction for
01:15:14interaction form that stable protein dynamics.
01:15:19This is super complicate with its difficult
01:15:24to take a picture of things about
01:15:29outcomes moving so all the experiments
01:15:34testing protein dynamics are almost indirect evidence
01:15:39of reason moving things and
01:15:43di di di open problem is the mechanism interaction with
01:15:47legal are small molecular vitamins Gratis proprio da qui.
01:15:57Water proteins that actually
01:16:00have designed to interact with water for instance.
01:16:03If then about how is possible water enter
01:16:06the sell out that form parts and the brain and water
01:16:12inside out of specific velocity
01:16:17and this is an open problem so methods that
01:16:22product how small modules
01:16:25interact with protein services are not really
01:16:29super because it's also complicate
01:16:32to think about the solution space for a simple sequence.
01:16:37The solution space in the possible ways you can can be
01:16:44combined options to force molecular it is this way More.
01:16:51This way larger than the number of
01:16:54you can have or for so think about you want to
01:16:57find a new small modules that beans
01:17:00specific pocket in the service and protein.
01:17:06AM so another thing that they just
01:17:10mansion some is an design so now.
01:17:14There are methods and techniques to design progress for instance.
01:17:20We want to proteins that is the specific site,
01:17:24you can input the politics sites.
01:17:29And then it generated the the state of
01:17:34the protein that should keep that site stable enough to
01:17:39be functional for this or Maybe you want
01:17:42protein with the specific surface on one side you may
01:17:46designed use a soft protein that in
01:17:51this position is specific shape specific surface.
01:17:56This is novel being seems like methods are promises
01:18:04on the front so just to give you the year of death of death of.
01:18:14This you can on from the directions on
01:18:19the smaller layer smaller level you are
01:18:24functional group chemical entities
01:18:27you have definition of molecular.
01:18:29Not only proteins, but also others us can define
01:18:33changes so single jeans how
01:18:38it is translated and into a tridimensionale protein chain.
01:18:47you for complex complex so combination of multiple changes
01:18:52to form a protein protein complex that stable and.
01:18:59You can have assembly so they are
01:19:02large structures where you have hundred of changes
01:19:06think about virus and that it is the envelope or di
01:19:13the container of a material of
01:19:17various is not just made this combination of proteins.
01:19:23And this is the individual components on the surface of virus.
01:19:29You can have take pictures videos,
01:19:31you can have pictures of sex and the use of course.
01:19:36This is more about imaging so it's
01:19:40about taking pictures and processing to
01:19:44dimensional Il biological material thinking more about
01:19:52dimensional dimensions and so you have
01:19:56demographic force for example
01:20:00so you can identifying shape of proteins.
01:20:03If they are very large using electron
01:20:07microscopi at this level you need
01:20:11other techniques because you need the solutions able to capture
01:20:14position outcomes a very small see.
01:20:20How is possible so there was an effort and effort is called
01:20:27protein data bank of PDB and actually
01:20:31its world wide effort is made of three major entities.
01:20:36There is a PDB in the U.S. PDB in Europe,
01:20:41PDB in Japan you see the world
01:20:44is the three main areas and essential II.
01:20:49If you work a generator information about dimensional coordinate.
01:20:57Protein you expected to
01:21:03summit the coordinate in one of tree Davis and.
01:21:11Their synchronized daily.
01:21:14So. What is not so generation?
01:21:24PDB is a process di coordinate code can
01:21:33take years of work so is very important that
01:21:37this project has started successful successful forum.
01:21:43Some years this is number one B this is only.
01:21:48Ehm. Uhm. No. Le coordinate
01:21:55second di detta presence information about
01:21:58properties of some positions for instance collections
01:22:04on constraints about this is
01:22:06this is based on other types of techniques,
01:22:09which is called and more in this
01:22:12is actually you can do experiments for once upon
01:22:17a time distance when you can not actually a get di
01:22:22coordinate of the entire is that the case.
01:22:30So di the way you summit is to this there is single entry point.
01:22:37This is one that it
01:22:40Il PDB Consortium of the three entities if you search for PDB.
01:22:48Documentation about the format are you should summit things are you
01:22:54should what's up to you should use to
01:22:57the process or to the metadata for your antisenso.
01:23:02Okay, so am the other keys is that there is
01:23:08number huge number of other database is that use PDB data source.
01:23:16This is a statistics not very updated in there
01:23:23is journal of
01:23:24clinical asset research Prestigioso journal It's actually.
01:23:31Publish or special issue every hear about
01:23:34new biological database is or updates to biological Databases in
01:23:39general and you see twenty sixteen more than two databases used
01:23:49DB data database database
01:23:55database sample important DB hits US hits,
01:24:04best of US news plus a number of
01:24:08other second resource sources use DB data as
01:24:13a network so what is the point of
01:24:18this database di idea is that we di coordinate
01:24:24they just provide information what is the shape of course to give
01:24:30a biological value or meaning to this coordinate you have
01:24:34to integrate the state of data with Information.
01:24:40Act that mutation can disruptive functional time and so on
01:24:47association of diseases and so so PDB is just about coordinate,
01:24:54of course or every entry you usually also have a companion.
01:25:04And the functional protein,
01:25:07but also have integrated information from
01:25:12other resources and other type
01:25:14of experimental like for instance association,
01:25:17which is it's not the best for for the state of information.
01:25:21The main goal is to describe the structure
01:25:24and the quality of the structures you are you are not.
01:25:29Last slide there is a number of sources
01:25:34directly Contributo integrativo BDB and
01:25:40Slab Milan contribute this resources in
01:25:46the aim in the biological system place,
01:25:52which mountain is to database.
01:25:55There is no one of this they are connected with.
01:26:02All stop year to model right to
01:26:07explain something about X-Ray Crystal orafi and.
01:26:12Open four for questions. Thank you.