Protein, proteins folds

P. L. Privalov, Physical Basis ofi the Stability ofi the Folded Conformations ofi Proteins Protein Folding, Freeman, New York, 1992 K. A. DiU, Biochemistry 29, 7133 (1990). 

In introductory biochemistry, one becomes familiar with amino acids (aa) and how they combine (polymerize) to become peptides and proteins. Proteins fold into three-dimensional shapes and become enzymes, the catalysts of... 

As has been discussed here, the reactions that occur upon radiolysis of dilute solutions of proteins in water are very much dependent upon the amino acid composition of the protein, protein folding (i.e. residues that are surface exposed), the presence of metal catalytic centers and the particular radicals that are generated in solution. As has been illustrated in the last two examples, radiation chemistry can serve as a probe of the redox processes that occur upon catalysis and, under very specific systems, can also serve to generate the substrate for enzyme catalysis. 

The tertiary structure of a protein is the three-dimensional arrangement of all the atoms in the protein. Proteins fold spontaneously in solution in order to maximize their stability. Every time there is a stabilizing interaction between two atoms, free energy is released. The more free energy released (the more negative the AG°), the more stable the protein. So a protein tends to fold in a way that maximizes the number of stabilizing interactions (Figure 23.11). 

Similarly, l-anilinonaphthalene-8-sulfonic acid (ANS) only emits in a hydrophobic environment, being almost completely quenched in aqueous solution. ANS and some other dyes, including 6-(p-toluidinyl)naphthalene-2-sulfo-nate, pyrene, l,6-diphenyl-l,3,5-hexatriene, fluorescein, and rhodamine derivatives attached to long acyl chains or to fatty acids that localize in the cellular membranes were used as probes for hydrophobic sites in proteins, protein folding, imaging of membranes of the cell, and solvent polarity. Pyrene-labeled fatty acids were used to detect the fusion of two membranes. When present in a membrane at sufficiently high concentrations, pyrene excimers (excited-state dimers) are formed that emit at 470 nm. Upon fusion with other membranes, probe concentration decreases, and excimer fluorescence is replaced by monomer fluorescence at 400 nm. This process can be monitored by ratiometric detection of pyrene labels. 

HS-DSC can also be used to study the denaturation of proteins, protein folding, helix-helix transitions and the motion of side-chains. A comparison of the transition with strict two-state behaviour can be made by comparing the observed HS-DSC curve with the theoretical curve derived using the van t Hoff relationship... 

FIG. 2.2 The three threads of information and structure in life DNA, RNA, and protein. Proteins fold into three-dimensional structures that can carry out chemistry inside, outside, and on the surface of cells. 

In the sequel, we first outline the basics of the deterministic global optimization approach, aBB, which has been used extensively to study the protein structure prediction, dynamics of protein-protein folding, and protein docking problems. This is followed by a comprehensive study of ab initio modeling for structure prediction of single-chain polypeptides in Section III. An... 

Both the structural and kinetic aspects of the protein-folding problem are complicated by the fact that folding takes place within a bath of water molecules. In fact, hydrophobic interactions are almost certainly crucial for both the relation of the sequence and the native structure, and the process by which a good sequence folds to its native structure. 

Asher S A and Chi Z H 1998 UV resonance Raman studies of protein folding in myoglobin and other proteins Biophys. 

Plenary 4. George J Thomas Jr et at, e-mail address thomasgj ,cctr.mnkc.edu (RS). Protein folding and assembly into superstructures. (Slow) time resolved RS probing of virus construction via protein assembly into an icosahedral (capsid) shell. 

C2.5 Introducing protein folding using simple models... 

Most reactions in cells are carried out by enzymes [1], In many instances the rates of enzyme-catalysed reactions are enhanced by a factor of a million. A significantly large fraction of all known enzymes are proteins which are made from twenty naturally occurring amino acids. The amino acids are linked by peptide bonds to fonn polypeptide chains. The primary sequence of a protein specifies the linear order in which the amino acids are linked. To carry out the catalytic activity the linear sequence has to fold to a well defined tliree-dimensional (3D) stmcture. In cells only a relatively small fraction of proteins require assistance from chaperones (helper proteins) [2]. Even in the complicated cellular environment most proteins fold spontaneously upon synthesis. The detennination of the 3D folded stmcture from the one-dimensional primary sequence is the most popular protein folding problem. 

From our perspective there are four major problems that comprise the protein folding enterjDrise. They are ... 

How to design sequences tliat adopt a specified fold [9] This is tire inverse protein folding problem tliat is vital to the biotechnology industry. There are some proteins tliat do not spontaneously reach tire native confomiation. In tire cells tliese proteins fold witli tire assistance of helper molecules referred to as chaperonins. The chaperonin-mediated folding problem involves an understanding of tire interactions between proteins. 

MES)==10 These results suggest tliat C(MES) grows (in all likelihood) only as In N with N. Thus tlie restriction of compactness and low energy of tlie native states may impose an upper bound on tlie number of distinct protein folds. 

C2.5.3.4 EXPLORING THE PROTEIN FOLDING MECHANISM USING THE LATTICE MODEL... 

The examples of modelling discussed in section C2.5.2 and section C2.5.3 are meant to illustrate tlie ideas behind tlie tlieoretical and computational approaches to protein folding. It should be borne in mind tliat we have discussed only a very limited aspect of tlie rich field of protein folding. The computations described in section C2.5.3 can be carried out easily on a desktop computer. Such an exercise is, perhaps, tlie best of way of appreciating tlie simple approach to get at tlie principles tliat govern tlie folding of proteins. 

Lorimer G H 1996 A quantitative assessment of the role of the ohaperonin proteins in protein folding in vivo FASEB J. 10 5-9... 

Lansbury P T 1999 Evolution of amyloids What normal protein folding oan tell us about fibrillogenesis and disease Proc. Nati Acad. Sci. (USA) 96 3342-4... 

Onuohio J N, Luthey-Sohulten Z A and Wolynes P G 1997 Theory of protein folding An energy landsoape perspeotive Ann. Rev. Phys. Chem. 48 545-600... 

Thirumalai D and Klimov D K 1999 Deoiphering the timesoales and meohanisms of protein folding using minimal off-lattioe models Curr. Opin. Stmct. Bid. 9 197-207... 

Garel T, Orland H and Thirumalai D 1996 Analytical theories of protein folding New Developments in Theoretical Studies of Protein Folding e6 R Elber (Singapore World Scientific) pp 197-268... 

Bryngelson J D and Wolynes P G 1987 Spin glasses and the statistical mechanics of protein folding Proc. Natl Acad. Sci. (USA) 84 7524-8... 

Dill K A, Bromberg S, Yue K, Fiebig K M, Yee D P, Thomas P D and Chan H S 1995 Principles of protein folding—a perspective from simple exact models Protein Sci. 561-602... 

Taketomi H, Ueda Y and Go N 1975 Studies on protein folding, unfolding, and fluctuations by computer simulation Int. J. Pept. Protein Res. 7 445-59... 

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