Thermodynamic properties Proteins

The use of computer simulations to study internal motions and thermodynamic properties is receiving increased attention. One important use of the method is to provide a more fundamental understanding of the molecular information contained in various kinds of experiments on these complex systems. In the first part of this paper we review recent work in our laboratory concerned with the use of computer simulations for the interpretation of experimental probes of molecular structure and dynamics of proteins and nucleic acids. The interplay between computer simulations and three experimental techniques is emphasized (1) nuclear magnetic resonance relaxation spectroscopy, (2) refinement of macro-molecular x-ray structures, and (3) vibrational spectroscopy. The treatment of solvent effects in biopolymer simulations is a difficult problem. It is not possible to study systematically the effect of solvent conditions, e.g. added salt concentration, on biopolymer properties by means of simulations alone. In the last part of the paper we review a more analytical approach we have developed to study polyelectrolyte properties of solvated biopolymers. The results are compared with computer simulations. 

Folded and unfolded proteins in solution are dense materials characterized in large part by different degrees of conformational flexibility and solvent exposure. Thus, packing is a foundational issue for their solution thermodynamic properties. Although the developments above... 

The insertion of proteins into intracellular membranes has incising effects upon the kinetic and thermodynamic properties of the corresponding biological interactions. Although diffusion in membranes is approx. 100-fold slower than in aqueous solution the probability for two molecules to meet... 

We may illustrate this approach to the determination of the nuclear factor by the elegant studies performed by Gray and co-workers, who have determined the thermodynamic properties and the rate temperature dependence for the electron transfer between Ru(NH3) covalently bound to the histidine residues of some proteins, and the redox eenter of these proteins [110, 111, 112, 113]. The experimental results obtained for cytochrome c [110] and azurin [111, 112] are very similar. Using the thermodynamic data and the value or the upper limit of Ea reported in these studies, we deduce from Eq. (23) ... 

Powell, K.D., Fitzgerald, M.C. Accuracy and precision of a new H/D exchange- and mass spectrometry-based technique for measuring the thermodynamic properties of protein-peptide complexes. Biochemistry 2003, 42, 4962-4970. 

It has been known that adsorption kinetics and/or thermodynamics of proteins depend on the electric or electrochemical properties of solid supports on which the proteins are adsorbed. This has led us to elucidate the effects of electrode potential on the adsorption behavior of avidin on the electrode surface. For this purpose, the electrode potential of a Pt electrode was varied systematically in the range of -0.5-+2.0 V in an avidin solution (pH 7.4). Although the data was somewhat scattered, a general trend was observed that the adsorption of avidin is suppressed by the application of a positive potential (+1.0-+2.0 V). This may be originating from the fact that avidin is a basic protein and has net positive charges in the solution of neutral pH. In the potential range tested, no significant acceleration in the adsorption was induced. 

For those systems we have studied so far, many classical ligand field features are successfully captured by LFMM e.g., the double hump variation of structural and thermodynamic properties due to the LFSE (73), o- (36,58,78) and -type (77) Jahn-Teller effects, the trans influence (21), and spin state effects (18,33,59). LFMM is equally at home with small molecules and large proteins and potential future coordination chemistry applications are enormous. 

Nicholls A, Sharp KA, Honig B. Protein folding and association insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins 1991 11 281-296. 

Belyakova, L.E., Semenova, M.G., Antipova, A.S. (1999). Effect of small molecule surfactants on molecular parameters and thermodynamic properties of legumin in a bulk and at the air-water interface depending on a protein structure in an aqueous medium. Colloids and Surfaces B Biointerfaces, 12, 271-285. 

H189E <1> (<1> comparable to wild type enzyme [26] <1> thermodynamics [29] <1> mutant retains ability for phosphorylation [34]) [26, 29, 34] Additional information <1, 3, 6, 12> (<1,3,6> overview on mutants [19] <1> N-terminal domain, thermodynamic properties [25,29] <3,6,12> enzyme deletion mutants, virulence of [31] <6> enzyme deletion mutant, alternative pathways [36] <1> fusion protein of enzyme plus the remaining three subunits of glucose phosphotransferase system and Ala-Pro-rich linker sequences [32]) [19, 25, 29, 31, 32]... 

An increase of intracellular adenosine levels can also be achieved by inhibition of nucleoside transport proteins. Mammalian nucleoside transport processes can be classified into two types on the basis of their thermodynamic properties. These classes are the concentrative, Na+-dependent transport processes and the equilibrative, Na+-independent processes. The corresponding transporters are called CNTs (concentrative nucleoside transporters) and ENTs (equilibrative nucleoside transporters) (Pastor-Anglada and Baldwin, 2001). 

Because of the apparent power of exchange at equilibrium to measure fluctuations in structure, there have been many attempts to use the procedure to determine pathways. We know from section Cl that this is a futile activity equilibrium measurements just give the relative thermodynamic properties of intermediates and not the pathway between them.53 The value of A Gex, the equilibrium constant between particular open and closed states of a protein derived from hydrogen exchange at equilibrium, is just such a thermodynamic measurement and does not give information about when that state is formed on a pathway. For example, con-... 

There is a severe practical problem in looking for correlations between the rate constants for folding of small proteins and their structural or thermodynamic properties—specific structural features can dominate the rate of folding. For example, we know from the protein engineering studies on barnase and CI2 that specific mutations can slow down the rate of folding by several orders of... 

We now see that mitochondria contain a variety of molecules—cytochromes, flavins, ubiquinone, and iron-sulfur proteins—all of which can act as electron carriers. To discuss how these carriers cooperate to transport electrons from reduced substrates to 02, it is useful to have a measure of each molecule s tendency to release or accept electrons. The standard redox potential, E°, provides such a measure. Redox potentials are thermodynamic properties that depend on the differences in free energy between the oxidized and reduced forms of a molecule. Like the electric potentials that govern electron flow from one pole of a battery to another, E° values are specified in volts. Because electron-transfer reactions frequently involve protons also, an additional symbol is used to indicate that an E° value applies to a particular pH thus, E° refers to an E° at pH 7. 

Nemethy, G., and Scheraga, H. A. The structure of water and hydrophobic bonding in proteins. III. The thermodynamic properties of hydrophobic bonds in proteins. J, Phys. Chem. 66,1773-1789 (1962). 

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