Macromolecules functions

Albumin (50-60 mg/ml) Albumin, one of the most important proteins in human plasma, is able to bind copper(II) tightly and iron weakly. Copper(II) bound to albumin is still effective in generating radical species in the presence of hydrogen peroxide. Thus macromolecules functioning by this mechanism are called sacrificial antioxidants, since the hydroxyl radical is generated locally on the protein and reacts at the specific site (Halli-well, 1988). The binding of copper ions to albumin may represent a protective mechanism overall, since the damaged albumin can be quickly replaced. 

Probing biological macromolecule functions with extrinsic fluorescence... 

Acetylation is a very common metabolic reaction which occurs with amino, hydroxyl or sulfhydryl groups. The acetyl group is transferred from acetyl-coenzyme A 2ind the reaction is catalysed by acetyltransferases. An important aspect of this kind of substitution is the genetic polymorphism of one acetyltransferase in humans, who are divided into fast and slow acetylators. In a few cases, the conjugates are further metabolized to toxic compounds, as is seen with isoniazid. Some evidence exists that acetylation of the antitubercular isoniazid leads to enhanced hepatotoxicity of the drug. ° Acetylation followed by hydrolysis and cytochrome P-450-dependent oxidation yields free acetyl radicals or acylium cations which may acetylate the nucleophilic macromolecule functions (Fig. 32.16). 

The structures of SH2 domains in the context of other protein modules provided much information on how these modules function within the context of a larger protein. However, the availibility of structures is just the first step of many which are needed to understand how macromolecules function. In this section, we describe solution studies of SH2 domains placed in the context of either larger protein fragments or full-length proteins that have provided information about the various mechanisms by which SH2 domains regidate protein function. 

On the other hand, owing to the rising demand for specialty polymers with novel properties and characteristics designed for specific applications, hyperbranched polymers have attracted much investigation in the past decades [30]. The growing strategy uses the symmetrical nature of the molecules to construct macromolecules functionalized at each end [31]. 

Functional Macromolecules. Functional macromolecules bear chemical groups, which differ in composition from the main polymer chain. The functional groups lend to polymer chains some specific properties, for example certain reactivity. This property is especially important for oligomers. 

Stouffer J M and McCarthy T J 1988 Polymer monolayers prepared by the spontaneous adsorption of sulphur-functionalized polystyrene on gold surfaces Macromolecules 2 1204-8... 

Among the main theoretical methods of investigation of the dynamic properties of macromolecules are molecular dynamics (MD) simulations and harmonic analysis. MD simulation is a technique in which the classical equation of motion for all atoms of a molecule is integrated over a finite period of time. Harmonic analysis is a direct way of analyzing vibrational motions. Harmonicity of the potential function is a basic assumption in the normal mode approximation used in harmonic analysis. This is known to be inadequate in the case of biological macromolecules, such as proteins, because anharmonic effects, which MD has shown to be important in protein motion, are neglected [1, 2, 3]. 

For a given potential energy function, one may take a variety of approaches to study the dynamics of macromolecules. The most exact and detailed information is provided by MD simulations in which one solves the equations of motion for the atoms constituting the macromolecule and any surrounding environment. With currently available techniques and methods it is possible... 

Unconstrained optimization methods [W. H. Press, et. al.. Numerical Recipes The Art of Scientific Computing, Cambridge University Press, 1986, Chapter 10] can use values of only the objective function, or of first derivatives of the objective function, second derivatives of the objective function, etc. HyperChem uses first derivative information and, in the Block Diagonal Newton-Raphson case, second derivatives for one atom at a time. HyperChem does not use optimizers that compute the full set of second derivatives (the Hessian) because it is impractical to store the Hessian for macromolecules with thousands of atoms. A future release may make explicit-Hessian methods available for smaller molecules but at this release only methods that store the first derivative information, or the second derivatives of a single atom, are used. 

To understand the function of a protein at the molecular level, it is important to know its three-dimensional stmcture. The diversity in protein stmcture, as in many other macromolecules, results from the flexibiUty of rotation about single bonds between atoms. Each peptide unit is planar, ie, oJ = 180°, and has two rotational degrees of freedom, specified by the torsion angles ( ) and /, along the polypeptide backbone. The number of torsion angles associated with the side chains, R, varies from residue to residue. The allowed conformations of a protein are those that avoid atomic coUisions between nonbonded atoms. 

Enzymes Degrading Macromolecules. Enzymes that degrade macromolecules such as membrane polysaccharides, stmctural and functional proteins, or nucleic acids, have all shown oncolytic activity. Treatment strategies include the treatment of inoperable tumors with pepsin (1) antitumor activity of carboxypeptidase (44) cytotoxicity of ribonudease (45—47) oncolytic activity of neuraminidase (48—52) therapy with neuraminidase of patients with acute myeloid leukemia (53) antitumor activity of proteases (54) and hyaluronidase treatment in the management of human soHd tumors (55). 

The overall scope of this book is the implementation and application of available theoretical and computational methods toward understanding the structure, dynamics, and function of biological molecules, namely proteins, nucleic acids, carbohydrates, and membranes. The large number of computational tools already available in computational chemistry preclude covering all topics, as Schleyer et al. are doing in The Encyclopedia of Computational Chemistry [23]. Instead, we have attempted to create a book that covers currently available theoretical methods applicable to biomolecular research along with the appropriate computational applications. We have designed it to focus on the area of biomolecular computations with emphasis on the special requirements associated with the treatment of macromolecules. 

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