Protein molecule

After completion of the human genome sequences in the year 2000, the challenge was immediately redirected to using these data to interpret the function of proteins. Nucleic acids and proteins are inseparable components of the process of life. Nucleic acids direct the production of proteins, but it is the proteins that carry out the body s functions. Today, research in nucleic acids is always deeply intertwined with research of proteins and vice versa. 

In Chapter 1, we introduced the concept of the protein. This chapter describes proteins in greater detail, including the fundamental principles that are emerging from post-human genome studies. The emphasis here is given to the sequence-structure relationship and how the protein is folded. 

The classical way to describe a protein is in terms of its primary structure, secondary stmcture, tertiary structure, and quaternary structure. All four types of structure are closely related. They are only four different ways to characterize the same protein. We begin with the classical way to describe a protein, starting with its primary stmcture. 

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The most familiar type of electrokinetic experiment consists of setting up a potential gradient in a solution containing charged particles and determining their rate of motion. If the particles are small molecular ions, the phenomenon is called ionic conductance, if they are larger units, such as protein molecules, or colloidal particles, it is called electrophoresis. 

In favourable contrast to molecular dynamics, BD allows molecular movements of realistically long duration to be simulated. Nevertheless, the practical number of protein molecules which can be simulated is only two since collective phenomena are often of crucial importance in detennining the course of interaction events, other simulation teclmiques, such as cellular automata [115], need to be used to capture the behaviour of large numbers of particles. 

Biological infonnation is also concerned witli tire analysis of biological messages and tlieir import. The fundamental premise of tire protein-folding problem section C2.14.2.2 is tliat tire full tliree-dimensional arrangement of tire protein molecule can be predicted, given only tire amino acid sequence, together witli tire solvent composition, temperature and pressure. One test of tire validity of tliis premise is to compare tire infonnation content of tire sequence witli tire infonnation contained in tire stmcture [169]. The fonner can be obtained from Shannon s fonnula ... 

Ermolina I V, Fedotov V D and Feldman Yu D 1998 Structure and dynamic behaviour of protein molecules in solution Physioa A 249 347-52... 

Kondo A, Oku S and FllgashItanI K 1991 Structural changes In protein molecules adsorbed on ultrafine silica particles J. Colloid Interfaoe Sc/. 143 214-21... 

Binding of Water in Cavities Inside Protein Molecules... 

The method described here becomes less suitable as the size of the ligand molecule increases. The problem of computing the cratic term for formation of complexes of two protein molecules have been discussed by others [34] [35]. 

The forces in a protein molecule are modeled by the gradient of the potential energy V(s, x) in dependence on a vector s encoding the amino acid sequence of the molecule and a vector x containing the Cartesian coordinates of all essential atoms of a molecule. In an equilibrium state x, the forces (s, x) vanish, so x is stationary and for stability reasons we must have a local minimizer. The most stable equilibrium state of a molecule is usually the... 

Therefore, modeling a protein molecule amounts to deciding on the atoms considered to be essential and to specifying the contribution of the various interactions to the potential. Since the work to find the global minimizer increases drastically (and possibly exponentially) with the dimension of x, it is customary to use for larger proteins a reduced description that treats only very few atoms in each amino acid as essential. 

Neural networks have been applied to IR spectrum interpreting systems in many variations and applications. Anand [108] introduced a neural network approach to analyze the presence of amino acids in protein molecules with a reliability of nearly 90%. Robb and Munk [109] used a linear neural network model for interpreting IR spectra for routine analysis purposes, with a similar performance. Ehrentreich et al. [110] used a counterpropagation network based on a strategy of Novic and Zupan [111] to model the correlation of structures and IR spectra. Penchev and co-workers [112] compared three types of spectral features derived from IR peak tables for their ability to be used in automatic classification of IR spectra. 

Eample For protein molecules with motions occurring at a frequency of about 1 cm the vibrational period is about 30 ps. Clearly, simulations of hundreds of picoseconds are necessary to probe adequately the motions of this system. 

Semi-empirical methods could thus treat the receptor portion of a single protein molecule as a quantum mechanical region but ab mdio methods cannot. However, both semi-empirical and ab initio methods could treat solvents as a perturbation on a quantum mechanical solute. In the future, HyperChem may have an algorithm for correctly treating the boundary between a classical region and an ab mdio quantum mechanical region in the same molecule. For the time being it does not. 

It is conventional to speak of three levels of structure in protein molecules ... 

Hydrogen bonding stabilizes some protein molecules in helical forms, and disulfide cross-links stabilize some protein molecules in globular forms. We shall consider helical structures in Sec. 1.11 and shall learn more about ellipsoidal globular proteins in the chapters concerned with the solution properties of polymers, especially Chap. 9. Both secondary and tertiary levels of structure are also influenced by the distribution of polar and nonpolar amino acid molecules relative to the aqueous environment of the protein molecules. Nonpolar amino acids are designated in Table 1.3. 

Figure 1.10 Helical conformations in polymer molecules, (a) A vinyl polymer with R substituents has three repeat units per turn, (b) The a helix of the protein molecule is stabilized by hydrogen bonding. [From R. B. Corey and L. Pauling,/ end. Inst. Lombardo Sci. 89 10 (1955).]...

Equation (8.97) shows that the second virial coefficient is a measure of the excluded volume of the solute according to the model we have considered. From the assumption that solute molecules come into surface contact in defining the excluded volume, it is apparent that this concept is easier to apply to, say, compact protein molecules in which hydrogen bonding and disulfide bridges maintain the tertiary structure (see Sec. 1.4) than to random coils. We shall return to the latter presently, but for now let us consider the application of Eq. (8.97) to a globular protein. This is the objective of the following example. 

Rigid, unsolvated spheres. Stokes law, Eq. (9.5), provides a relationship between f and the radius of the particle. Since this structure is a reasonable model for some protein molecules, experimental D values can be interpreted, via f, to yield values of R for such systems. Note that this application can also yield a value for M, since M = N pj [(4/3)ttR ], where pj is the density of the unsolvated material. 

Figure 9.4b shows a theoretical f/fQ contour for a value of this ratio equal to 1.45. As noted in the discussion of this figure in Sec. 9.3, the intersection of the f/fQ and [77] contours permits the state of solvation and ellipticity of such a protein molecule to be characterized uniquely. 

Protein molecules extracted from Escherichia coli ribosomes were examined by viscosity, sedimentation, and diffusion experiments for characterization with respect to molecular weight, hydration, and ellipticity. These dataf are examined in this and the following problem. Use Fig. 9.4a to estimate the axial ratio of the molecules, assuming a solvation of 0.26 g water (g protein)"V At 20°C, [r ] = 27.7 cm g" and P2 = 1.36 for aqueous solutions of this polymer. 

Hydroxylated amino acids (eg, 4-hydroxyproline, 5-hydroxylysine) and A/-methylated amino acids (eg, /V-methylhistidine) are obtained by the acid hydrolysis of proteins. y-Carboxyglutamic acid occurs as a component of some sections of protein molecules it decarboxylates spontaneously to L-glutamate at low pH. These examples are formed upon the nontranslational modification of protein and are often called secondary protein amino acids... 

Measuring Protein Sta.bihty, Protein stabihty is usually measured quantitatively as the difference in free energy between the folded and unfolded states of the protein. These states are most commonly measured using spectroscopic techniques, such as circular dichroic spectroscopy, fluorescence (generally tryptophan fluorescence) spectroscopy, nmr spectroscopy, and absorbance spectroscopy (10). For most monomeric proteins, the two-state model of protein folding can be invoked. This model states that under equihbrium conditions, the vast majority of the protein molecules in a solution exist in either the folded (native) or unfolded (denatured) state. Any kinetic intermediates that might exist on the pathway between folded and unfolded states do not accumulate to any significant extent under equihbrium conditions (39). In other words, under any set of solution conditions, at equihbrium the entire population of protein molecules can be accounted for by the mole fraction of denatured protein, and the mole fraction of native protein,, ie. 

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