Proteins crystals, functional properties

The molecular dynamics unit provides a good example with which to outline the basic approach. One of the most powerful applications of modem computational methods arises from their usefulness in visualizing dynamic molecular processes. Small molecules, solutions, and, more importantly, macromolecules are not static entities. A protein crystal structure or a model of a DNA helix actually provides relatively little information and insight into function as function is an intrinsically dynamic property. In this unit students are led through the basics of a molecular dynamics calculation, the implementation of methods integrating Newton s equations, the visualization of atomic motion controlled by potential energy functions or molecular force fields and onto the modeling and visualization of more complex systems. 

A powerful aspect of protein crystallography is that once the native structure is known, various cofactors or enzyme substrate analogs can be bound to the molecule in the crystal. By simply measuring the diffraction intensities, we can compute a new map that allows direct and explicit examination of the structural interactions between the native protein and its substrate or cofactor molecules. Detailed analysis of these interactions has provided much of the foundation for our current understanding of many protein catalytic and functional properties. 

A number of functional studies have shown that the partially ligated species and valency hybrid Hbs exhibit slowly interconverting conformation states. Some of them have properties that are intermediate between those associated with the T- and R-quaternary conformations (Cassoly and Gibson, 1972 Samaja et al., 1987 Sharma, 1989 Berjis et al., 1990). Thus, one needs to be careful in making correlations between a given crystal structure of a specific Hb species and its functional properties. It should be kept in mind that crystallization is a selective procedure, i.e., it selects those proteins with specific structures that are crystallizable under a given set of crystallization conditions. The structures of these crystallized proteins may not be the dominant ones when function is measured under solution conditions different from those used in crystallizing the proteins. 

As with pH, proteins may vary in solubility as a function of temperature, and some are quite sensitive. One can take advantage of this property with both bulk and microtechniques (Jacoby, 1968 McPherson, 1999). Many of the earliest examples of protein crystallization were based on the formation of concentrated solutions at elevated temperatures followed by slow cooling. Osborne in 1892 successfully crystallized over 20 plant seed globulins by cooling relatively crude extracts from 60°C to room temperature in the presence of varying concentrations of sodium chloride. 

Self-assembly of matter (or the formation of superstructures by means of non-covalent bonds) is a fascinating field of research. The formation of crystals and liquid crystals by atoms or molecules is just one example. Also within a larger molecule with a lot of conformational freedom, such as a polyamide chain or a protein, certain conformations are stabilized by secondary interactions, such as hydrogen bonds, which is essential for their properties (eg, mechanical properties of polyamides and functional properties of proteins). Secondary interactions in supramolecular structures play an important role for many processes in living cells (1). Various aspects of self-assembly have been presented in books (2-4) and in a recent review (5). This article deals with the self-assembly (or self-organization) of synthetic macromolecules, namely block copolymers, principally teming triblocks (see Block Copolymers). 

One particular asset of structured self-assemblies is their ability to create nano- to microsized domains, snch as cavities, that could be exploited for chemical synthesis and catalysis. Many kinds of organized self-assemblies have been proved to act as efficient nanoreactors, and several chapters of this book discnss some of them such as small discrete supramolecular vessels (Chapter Reactivity In Nanoscale Vessels, Supramolecular Reactivity), dendrimers (Chapter Supramolecular Dendrlmer Chemistry, Soft Matter), or protein cages and virus capsids (Chapter Viruses as Self-Assembled Templates, Self-Processes). In this chapter, we focus on larger and softer self-assembled structures such as micelles, vesicles, liquid crystals (LCs), or gels, which are made of surfactants, block copolymers, or amphiphilic peptides. In addition, only the systems that present a high kinetic lability (i.e., dynamic) of their aggregated building blocks are considered more static objects such as most of polymersomes and molecularly imprinted polymers are discussed elsewhere (Chapters Assembly of Block Copolymers and Molecularly Imprinted Polymers, Soft Matter, respectively). Finally, for each of these dynamic systems, we describe their functional properties with respect to their potential for the promotion and catalysis of molecular and biomolecu-lar transformations, polymerization, self-replication, metal colloid formation, and mineralization processes. 

Testicular hyaluronidase hydrolyses the biopolymer to 4,6, 8,10,12,14,16, 18, 20 and other disaccharide fragments [139]. Disaccharides are able to crystallize and other oligosaccharides can form liquid-crystalline structures. Thus, low molecular weight liagments of all biopolymers (hyaluronan, nncleic acid, proteins polyphosphate and other polycation and polyanion biopolymers) can form Uquid-crystalline biological structures with intermediate states, acquiring new functional properties [140-143]. 

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