Macromolecule biological

H ACTIVE FIGURE 1.B Informational macromolecules. Biological macromolecules are informational. The sequence of monomeric units in a biological polymer has the potential to contain information if the order of units is not overly repetitive. Nucleic acids and proteins are informational macromolecules polysaccharides are not. Sign in atwww.thomsonedu.com/login to explore an interactive version of this figure. 

R. Langer, D. Lund, K. Leong, J. Folkman, Controlled release of macromolecules biological smdies, J. Control. Release 2 (1985) 331-341. 

Danger, R., Lund, D., Leong, K., Folkman, J., 1985. Controlled release of macromolecules biological studies. Journal of Controlled Release 2, 331—341. 

Structural alerts or chemical motifs known to be associated with toxicity through either the parent compound or reactive metabolites have also been used to predict potential toxicity from chemical structures. These expert algorithms appear in commercial software programs and in onhne open access sites. For instance, there are seven chemical domains that are used to define and predict the covalent interaction between a chemical and a macromolecule (biological target) that leads to an initiating event at the beginning of an AOP [34]. These include Michael addition, acylation, Schiff base formation, aromatic nucleophilic substitution, unimolecular... 

Many complex systems have been spread on liquid interfaces for a variety of reasons. We begin this chapter with a discussion of the behavior of synthetic polymers at the liquid-air interface. Most of these systems are linear macromolecules however, rigid-rod polymers and more complex structures are of interest for potential optoelectronic applications. Biological macromolecules are spread at the liquid-vapor interface to fabricate sensors and other biomedical devices. In addition, the study of proteins at the air-water interface yields important information on enzymatic recognition, and membrane protein behavior. We touch on other biological systems, namely, phospholipids and cholesterol monolayers. These systems are so widely and routinely studied these days that they were also mentioned in some detail in Chapter IV. The closely related matter of bilayers and vesicles is also briefly addressed. 

An experimental teclmique that is usefiil for structure studies of biological macromolecules and other crystals with large unit cells uses neither the broad, white , spectrum characteristic of Lane methods nor a sharp, monocliromatic spectrum, but rather a spectral band with AX/X 20%. Because of its relation to the Lane method, this teclmique is called quasi-Laue. It was believed for many years diat the Lane method was not usefiil for structure studies because reflections of different orders would be superposed on the same point of a film or an image plate. It was realized recently, however, that, if there is a definite minimum wavelengdi in the spectral band, more than 80% of all reflections would contain only a single order. Quasi-Laue methods are now used with both neutrons and x-rays, particularly x-rays from synclirotron sources, which give an intense, white spectrum. 

Wuthrich K 1996 Biological macromolecules structural determination in solution Encyclopedia of NMR yo 2, ed D M Grant and R K Harris (Chichester Wiley) pp 932-9... 

Interactions between macromolecules (protems, lipids, DNA,.. . ) or biological structures (e.g. membranes) are considerably more complex than the interactions described m the two preceding paragraphs. The sum of all biological mteractions at the molecular level is the basis of the complex mechanisms of life. In addition to computer simulations, direct force measurements [98], especially the surface forces apparatus, represent an invaluable tool to help understand the molecular interactions in biological systems. 

Most biological catalysts are enzymes, i.e., proteins, which are macromolecules (polypeptides) fonned by biopolymerization of amino acids (with elimination of water) some enzymes are huge, with hundreds of monomer units. The 20 amino acid monomers occurring in nature. 

Much of tire science of biocompatibility can be reduced to tire principles of how to detennine tire interfacial energies between biopolymer and surface. The biopolymer is considered to be large enough to behave as bulk material witli a surface since (for example) a water cluster containing only 15 molecules and witli a diameter of 0.5 nm already behaves as a bulk liquid [132] it appears tliat most biological macromolecules can be considered to... 

Guntert P 1998 Structure calculation of biological macromolecules from nmr data 1998 Q. Rev. Biophys. 31 145-237... 

Fig. 1. Structure adapted hierarchical description of Coulomb interactions in biological macromolecules. Filled circles (level 0) represent atoms, structural units (li vel 1) are surrounded by a single-line border, and clusters (level 2) are surrounded by a double-line border.

MD simulations are valuable tools if one wants to gain detailed insight into fast dynamical processes of proteins and other biological macromolecules at atomic resolution. But since conventional MD simulations are confined to the study of very fast processes, conformational flooding represents a complementary and powerful tool to predict and understand also slow conformational motions. Another obvious application is an enhanced refinement of Xray- or NMR-structures. 

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]. 

Much work remains to be done in the development of this approach to explore the advantages and limitations of the method. The method will be extended to force fields that include torsional terms large systems such as biological macromolecules will also be treated. 

Besides the MDL Molfile formal, other file formats are often used in chemistry SMILES has already been mentioned in Section 2.3.3. Another one, the PDB file format, is primarily used for storing 3D structure information on biological macromolecules such as proteins and polynucleotides (Tutorial, Section 2.9.7) [52, 53). GIF (Crystallographic Information File) [54, 55] is also a 3D structure information file format with more than three incompatible file versions and is used in crystallography. GIF should not be confused with the Chiron Interchange Formal, which is also extended with. cif. In spectroscopy, JCAMP is apphed as a spectroscopic exchange file format [56]. Here, two modifications can be... 

PDB files were designed for storage of crystal structures and related experimental information on biological macromolecules, primarily proteins, nucleic acids, and their complexes. Over the years the PDB file format was extended to handle results from other experimental (NM.R, cryoelectron microscopy) and theoretical methods... 

The visuahzation of hundreds or thousands of connected atoms, which are found in biological macromolecules, is no longer reasonable with the molecular models described above because too much detail would be shown. First of aU the models become vague if there are more than a few himdied atoms. This problem can be solved with some simplified models, which serve primarily to represent the secondary structure of the protein or nucleic acid backbone [201]. (Compare the balls and sticks model (Figure 2-124a) and the backbone representation (Figure 2-124b) of lysozyme.)... 

Another way of calculating the electrostatic component of solvation uses the Poisson-Boltzmann equations [22, 23]. This formalism, which is also frequently applied to biological macromolecules, treats the solvent as a high-dielectric continuum, whereas the solute is considered as an array of point charges in a constant, low-dielectric medium. Changes of the potential within a medium with the dielectric constant e can be related to the charge density p according to the Poisson equation (Eq. (41)). 

Ligand A ligand is a molecule binding to a biological macromolecule. 

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