Hydrophobic And Hydrophilic Interaction In Protein Folding Biology Essay

Hydrophobic And Hydrophilic moveion In Protein Folding Biology EssayReview the mechanism of protein bend dexterModule Enzyme Technology and BiocatalystsModule leader Prof. Steve ForsytheProteins atomic play 18 the bio molecules which play pivotal role in this living world. They atomic number 18 creditworthy for prospect of authorized characters in various types of prison cells and constitute around 50% of the total cell dried mass. Proteins be the chain of aminic bitings which binds with polypeptide gumptionb angiotensin-converting enzyme and then fold in a unique 3D ( inbred) view by which protein carriage rails break through. Various forces and factors are responsible for protein sheep pen .If right expression of the protein f tout ensemble(prenominal) non take place, it ordain cause disorders in human body. numerous indispositions uniform Alzheimers Parkinson, cystic fibrosis etcetera(Baldwin 2007) is caused receivable to improper plica of prote ins. For proper expression of protein, the amino acid chain should be in its unique 3D social organisation. Some measures proteins require sponsor in sheepcote, molecules which service in the plica are k straight as chaperones. These molecules benefactor in the faithful of the veritable protein molecules and also prevent the un crimp of the molecules.In this assignment, I deal assay to describe the mechanism of the protein congregation and effect of various factors which influence protein fold by taking into consideration the present increments in our understanding of thermodynamics and kinetics of protein.INTRODUCTIONProtein folding refers to the march by which a protein assumes its characteristic organize, cognize as the native render. Protein folding is genuinely complex mechanism and bulky development in its understanding has been achieved in last 20years due to the development and use of virtually sophisticated modern techniques like X balance beam Crys tallography, N.M.R, and Mass Spectrometry etc. In the last few decades, we convey managed to find the 3D social organisation of various proteins and how actually protein folding takes place. In the complex process of protein folding, various factors act together to construct item 3D bodily social organize of a protein. Protein folding is a very prompt process taking milliseconds to seconds.Due to high(prenominal) gear speed of folding, it is not likely to find each and every possible con fundamental law in fractions of time. Levinthal state that each protein elicit possibly make millions of pathway modality by which a desired 3D pattern can be achieved. By orbit of ordinarys we can understand the mechanism or pattern on which protein folding works. But it is impossible to find bring out(a) all possible organize of protein molecules.Protein folding study uses denaturants which help to denature the protein. The logic is to use denaturing conditions videlicet high pH, Temp, Pressure etc to stop folding at intermediate stages (Stop coalesce technique) to study these intermediates, thereby generating an overview of the whole process. Fully folded social system is also k immediatelyn as native complex body part. Protein folding studies have also been done in in-vivo and in-vitro conditions. In in- vivo protein folding, some metal ions act as cofactors. These cofactors stabilise and speed up protein folding and finally help to achieve native stage .Macromolecules like chaperones initiate protein folding, helping the protein molecule to retain its folded validation and making it unchanging. In-vitro engrossment of macromolecules is very less, around 1% of what is originally present in the cell. So inside cell, these molecules also affect protein perceptual constancy and make them more stable than in vitro (Rumfeldt et al. 2008)Protein folding can be a two stages or multistage process, depending upon the type of rank. A single point mutati on can alter folding from two stages to multistage and vice-versa .Some previous studies show that protein sequences of less than 80 amino acids prefer two stage folding and large protein sequences having more than cxxx amino acids prefer multi stage folding. Later studies have shown that sequences rich in F and G amino acids prefer two stages folding where as sequences rich in C, H, L and R amino acids prefer multistage folding (Ma, Chen Zhang 2007)PROTEINS FOLDINGHydrophobic and deliquescent interactionProteins are do of amino acids and joined by polypeptide bonds leads to formation of polypeptide backbone. We have only 20 type of the amino acids .whose combinations code for much(prenominal) complex twist and folding .These amino acids can be divide in two groups one is hydrophilic or opposite group and other(a) is aquaphobic or non paired group and their interaction with the cytoplasm make them folded(Trevino, Scholtz grounds 2007) arctic OR HYDROPHILIC amino ACIDNON -POLAR OR HYDROPHOBIC AMINO ACIDASPARTIC ACID DALANINE AGLUTAMIC ACID Egenus Glycine GARGNIN RVALINE VLYSINE KLEUCINE LHISTIDINE HISOLEUCINE IASPARAGINE NPROLINE PGLUTAMINE QPHENYLALANINE FSERINE SMETHIONINE MTHREONINE Ttryptophane WTYROSENE YCYSTEINE CIn the early stages of research, problem was wherefore protein folds to a specific social structure and which part of the protein carried information for the folding and afterwards on this was find that primary structure of the protein code for the final 3D structure. Hydrophilic and hydrophobic interactions of the amino acids adjust protein it such a counselling that it suffers minimum repulsion and problem from the surrounding. In folded state of protein all hydrophilic amino acid molecules pursue at the other side and interact with weewee in the cytoplasm and hydrophobic molecule come at the inner side of the molecule and dont show all reaction and attractive feature with water molecules and finally protein folding take pl ace in such a way that suffer minimum repulsion (Baldwin 2007)All amino acids have different energetic in secondary structure. There are many chameleon sequences in protein structure which can be interpreted as of import curl or beta sheets depending upon the tertiary structure of protein. These chameleon are stabilised by hydrophobic forces (Chen et al. 2008)Fig.a shows yel clinical depression warp hydrophobic molecules inner side of structureFig.b shows folding takes place and keeps hydrophobic molecules in inner side(Chen et al. 2008)Apart from these interactions atomic number 1 adhere is very strategic in the protein folding.Hydrogen attach takes place between hydrogen and electronegative atomsIn the maintenance of the native structure hydrogen bonding present in between the polypeptide amino acid chain which implemental in the formation of the secondary, tertiary and quaternary structure of the proteins. Hydrogen bonding also interacts between polar and side chain resi dues with the surrounding water molecules. During the denaturing of the protein hydrogen bond between protein molecules break and native structure of protein dotty (Djikaev, Ruckenstein 2010) Hydrophobic interactions are also responsible for the protein folding. During hydrophobic interactions amino acids which are non polar or hydrophobic they align themselves in such a way that all hydrophobic come together and all hydrophilic molecules make hydrogen bonds with water molecules, all hydrophobic amino acid come in to inner side of the protein molecules and formation of the nuclei take place which is hydrophobic these interaction further helpful in the secondary, tertiary structure and due to this protein stabilise and help to achieve native structure because hydrophobic molecules will not interact with water and evermore have hideous attitude toward water and let the protein in the folded form and finally such type of the folding take place in which molecule have hydrophobic core and all hydrophilic molecules in outer boundary of the folded structure(Berezovsky et al. 2001) innocuous energy and due south (G, E)Gibbs disengage energy (G) is also define as the amount of the energy which is free and this can also be defined as the pass judgment of unstableness and this measured by fair equatingG= H-TSG=free energy, H=enthalpy, S=entropy, T= temperature stochasticity (S) is defined as degree of randomness in any transcription, in terms of protein folding this can be define as the measure of the possible structure in the protein molecule at that take to be of the entropy. reciprocal ohm is responsible for the possible out come of protein as much high would be entropy as much high number of the confirmation would form. To minimise the entropy in the protein folding various force come in play like hydrogen bonds, salt bridges, disulphide bonds etc. these bonds help to reduce the entropy and favour protein folding(Brady, Sharp 1997)BOLTZMANN worked on the e ntropy and give us a very useful relation between atomic theory and entropy. Boltzmann proposed an equating which shows that entropy in any go arounded protein structure is tally to the product of his unending(KB) and natural log of number of all possible states which any protein can adopt(S)S = KB * NATURAL LOG (S)KB=Boltzmann constantProtein folding prefers low judge of entropy and follows that smallest path in which pass judgment of entropy is low. At different value of the entropy different number of structure could be present and finally all structure will vanished and one structure would be present at the minimum value of entropy, which is our native structure (Weikl, Dill 2003)Enthalpy (H) is also responsible for protein folding. This is also known as the measure of the total energy of the system including ingrained energy (U). P and V are the pressure and volume of systemH= U+P*VSo, we should search for such structure which have low value of enthalpy then the free ener gy, because which structure have low value of enthalpy that will have low value of free energy too(Brockwell, Smith Radford 2000)Gibbs free energy equation is the single solution for all protein folding problem. Gibbs equation shows that in outcome of protein folding, stable state will have minimum value of G. unfolded state have higher free energy then the folded one and protein folding have many intermediates, This stage is less populated stage and have maximum energy in the whole system, all above point of reference factor in the Gibbs equation adjust and finally erect such folded state in which value of G is minimum and this is known as fully folded and stable confirmation(Finkelstein, Badretdinov 1997)(www.biology-online.org/articles/statistical_thermodynamics_taking_walk.html)ChaperonesChaperones are bio molecules which participate in the protein folding. Proteins need swear outance in the folding and binds with cofactors .which allow them to fold properly .these cofacto r known as chaperones. These chaperones bind with the protein as N terminus of the protein formed and leave ribosome and until and unless protein learn his fully active 3D state and become functional(Tomala, Korona 2008) Chaperones are not only helping in the enlighten protein folding but they also help protein to maintain its correct 3D structure and prevent them to unfold .these molecules comes in to play when cell is under stress due to well-to-do conditions are not present and they also known as the H.S.P (heat daze protein).these molecular chaperones are HSP40(Dnaj), HSP60(GroEl), HSP70(Dnak) etc.(Rikhvanov, Romanova Chernoff 2007)Copied from Yon, Betton 1991Mode of actionChaperones recognise non native protein structure by their exposed hydrophobic regionsChaperones action is driven by adenosine triphosphate and for the activity of the chaperones assistance protein folding need of energy, which is provided by the ATP. These chaperones bind with the intermediate and unfold ed protein structure by the utilisation of the ATP intermediates or random curl up structure are unfolded and again they are fold in the correct 3D structure (NATIVE structure).Chaperones molecules are task specific that are different molecules perform different functions. For exampleHSP70/40They prevent aggregation and misfolding of impertinently synthesised protein molecules.HSP60They unfold intermediate and then fold them properly in to native structureChaperones are like catalyst, they enhance wander of protein folding and assist protein folding to native structure and after the formation of the native structure they separated. As like catalyst they take energy for the initiation of the processChaperones activity is much specialised, in stress condition protein get mutated, denature, and aggregate. Which whitethorn cause some wrong expression and code for some disease .In such situations they are enough capable to provide personalised discussion to different protein (Yon, Betton 1991)They can easily point out that which protein intermediate structure need to be degraded and which protein intermediate to be stabilise in the native structure and path should be follow for this process. In some mutation destabilise protein can be easily stabilized by HSP70 and some over expression of the specific chaperones. For example In bacterium HSP70 bind with the protein polypeptide chain during translation after the synthesis some protein released for expression and some may attached for some specialised folding and al intimately destabilise polypeptide chain degraded by chaperones (Tomala, Korona 2008)Chaperones activity is not simple they have multiple steps in their folding mechanism. Some chaperones required some other chaperones intermediate as substrate and then they provide native structure.Hsp90/70 mechanism chainSome chaperones may responsible for disease. it has been found that HSP90 enhance crabby person development because many mutated protein matur e in the figurehead of the HSP90 and cause cancer , repressing HSP90 such type of cancer can be able to prevent but problem associated with this is due to this action some non mutagenic protein will be degrade and not express and cause problem. But on other side HSP70 acts as grievous repressor in neurodegenerative disease and prevent this disease in the fruit flies (Tomala, Korona 2008)Models of protein homunculusling and structure predictionPlaxco and co-worker modelThis model shows that high degree of correlation between folding rate and structural properties of protein explain on the priming coat of pass order (CO). This can be cross validated from various experiments that folding rate and contact order are dependent to each other., Lis the sequence spaceNis the total number of inter-residue atomic contactsLijis the sequence separation of contacting residuesiandjKuznetsov and rackovsky showed that structural found determinants can serve as good determinants of folding rat e and many other researchers searching for which structural and sequence based determinants can serve as unique predictor of folding rate (Shakhnovich 2006)Dokholyan and co-workers modelThey use simple protein model and find out transition state of src homology 3(SH3) to find out contribution of each amino acid in transition state. They calculate value and on this basis they find high correlation between simulation and experimental value .in the end of their experimental model they conclude that L24 and G24 are two most important residues in the folding of proteinsPhysics and bioinformatics based modelsPhysics models are very helpful to understand protein folding rate and route to folding. These physical science based models help to understand the various forces and their dynamics in protein folding. These models help to understandConformational changes in proteinMechanism of folding, enzyme catalysis, mode of action proteinResponse to ph salt and denaturants(Brockwell, Smith Ra dford 2000)Bioinformatics is very important tool to find out the structure and folding pattern of the protein molecules. In this we add our computer based program along with these physics model and within the fraction of time provide us 3D structure of protein. Various databases on tissue are present which contain information regarding proteins only like NCBI, PUBMED etc. these databases contain all information about proteins by the comparison of our alien sequence using bioinformatics tools with these databases we can find out possible structure and folding pattern and helpful in drug discovery, possible lighten against disease etc. in a flash, how collectively these factors worksAfter having the knowledge of these factors now we can easily understand how they act and result to the fully folded 3D structure. Primary structure of protein code for 3D structure and all above factors participate to provide a functional unit. initially primary structure of protein are made of differe nt type of amino acids on the poly peptide back bone and just after the production of the N-terminus protein folding starts and secondary structures alpha helix and beta sheets are formed.In alpha helix all amino acid chain remain in the periphery of the helix and this structure formed due to hydrogen bonding and di-sulphide bonding (Trevino, Scholtz Pace 2007)After the formation of secondary structure, tertiary structure these hydrophobic interaction, hydrogen bonding and charge on the molecule come it to the play now this protein molecule structure fold in such a way to minimise all these forces and try to give an stable confirmation to protein(Chen et al. 2008) still energy and entropy act simultaneously. After attachment of these secondary structures stability is not uniform in the whole tertiary structure. There may be possibility that two stable structures are joining by unstable and less stable strands and in that subject field folding take place in such a way to minimise t he free energy of the system. This type of stage is known as the intermediate stage. In this stage all amino acids are attached in the structure but the entropy of the system is high and due to which this show high presence of free energy and may have the millions of the possibilities of the intermediate structure. Now protein starts folding from intermediate to the stable or native structure by minimising the interaction between the molecules. Due to which all the hydrophobic or non polar amino acid come in the centre of the structure and the formation of hydrophobic core take place of 3D structure and all polar or hydrophilic molecules come at the periphery of the 3D structure(Chen et al. 2008). Out of millions of the possibilities there are many path which favour this folding in term of having minimum energy and protein molecule select that path which is shortest and this may contain several steps in folding and ultimately leads to the formation of native 3D structureCopied from Ma, Chen Zhang 2007There is always some equilibrium in some folded and intermediates state and molecules may be aggregate. this depend upon the pH, Temp, Pressure and denaturation agents and the protein structure destabilise it start affecting other native protein structure in this stage chaperones act as cofactors and help in the and maintaining native structure of protein(Ma, Chen Zhang 2007)SUMMARYIn the protein folding 3D structure of protein plays an important role in the protein expression and their function. education regarding protein folding is present in the primary structure of the protein which bioenergetics can be determined by bound amino acid. Hydrophobic forces play an important role. They all concentrate at the centre of the molecules and hydrophilic at the periphery of the structure. Hydrogen bonding plays an important role due to which all polar molecules bound with the surrounding medium in cell and makes protein molecule structure rigid and compressed.Protein folding is a spontaneous process in which entropy of the molecule is decreasing and finally provides a folded structure. Protein native structure must have low value of Gibbs free energy, entropy, and enthalpy and lower the value, higher will be the degree of protein stability. Protein may unfold due to the presence of the unfavourable condition like temp, pressure, pH, and denaturing agent. In such a case special type of molecules help in the folding known as chaperones and helpful in maintaining native structure of protein.