Proteins and Nucleic Acids

Volkov, S.N. Conformational transitions and the mechanism of transmission of long-range effects in DNA. Preprint ITP-88-12E, Kiev (1988) 22 Krumhansl, J.A., Alexander, D.M. Nonlinear dynamics and conformational exitations in biomolecular materials. In Structure and dynamics nucleic acids and proteins. (Clementi, E., Sarma, R.H., eds) Adenine Press, New York (1983) 61-80... 

The Pullman method is a combination of the Del Re method for computing the a component of the charge and a semiempirical Hrickel calculation for the 7t portion. It has been fairly successful in describing dipole moments and atomic charges for nucleic acids and proteins. 

Weiner, S.J. Kollman, P.A. Case, D.A. Singh, U.C., Ohio, C. Alagona, G. Profeta Jr., S. Weiner, P. Anew force field for molecular mechanical simulation of nucleic acids and proteins 7 Am. Chem. Soc. 106 765-784, 1984. 

A. Ducruix and R. Giege (Eds), Crystallisation of Nucleic Acids and Proteins, IRL Press, Oxford, 1992. ISBN 0199632456. 2nd Edn, Oxford University Press, Oxford, 1999. ISBN 0199636788. 

Crystallisation. The ultimate in purification of proteins or nucleic acids is crystallisation. This involves very specialised procedures and techniques and is best left to the experts in the field of X-ray crystallography who provide a complete picture of the structure of these large molecules. [A. Ducruix and R. Gieg6 eds. Crystallisation of Nucleic Acids and Proteins A Practical Approach, 2nd Edition, 2000,... 

To date, a number of simulation studies have been performed on nucleic acids and proteins using both AMBER and CHARMM. A direct comparison of crystal simulations of bovine pancreatic trypsin inliibitor show that the two force fields behave similarly, although differences in solvent-protein interactions are evident [24]. Side-by-side tests have also been performed on a DNA duplex, showing both force fields to be in reasonable agreement with experiment although significant, and different, problems were evident in both cases [25]. It should be noted that as of the writing of this chapter revised versions of both the AMBER and CHARMM nucleic acid force fields had become available. Several simulations of membranes have been performed with the CHARMM force field for both saturated [26] and unsaturated [27] lipids. The availability of both protein and nucleic acid parameters in AMBER and CHARMM allows for protein-nucleic acid complexes to be studied with both force fields (see Chapter 20), whereas protein-lipid (see Chapter 21) and DNA-lipid simulations can also be performed with CHARMM. 

FIGURE 1.10 The sequence of monomeric units in a biological polymer has the potential to contain information if the diversity and order of the units are not overly simple or repetitive. Nucleic acids and proteins are information-rich molecules polysaccharides are not. 

FIGURE 1.25 The virus life cycle. Viruses are mobile bits of genetic iuformatiou encapsulated in a protein coat. The genetic material can be either DNA or RNA. Once this genetic material gains entry to its host cell, it takes over the host machinery for macromolecular synthesis and subverts it to the synthesis of viral-specific nucleic acids and proteins. These virus components are then assembled into mature virus particles that are released from the cell. Often, this parasitic cycle of virus infection leads to cell death and disease. 

A New Force Field for Molecular Mechanics Simulation of Nucleic Acids and Proteins... 

Dacarbazine is activated by photodecomposition (chemical breakdown caused by radiant energy) and by enzymatic N-demethylation. Formation of a methyl carbonium ion results in methylation of DNA and RNA and inhibition of nucleic acid and protein synthesis. Cells in all phases of the cell cycle are susceptible to dacarbazine. The drug is not appreciably protein bound, and it does not enter the central nervous system. 

However both classes, nucleic acids and proteins, are linear polymers in which the linear (nucleobase or amino acid) sequence encodes the three-dimensional structure and function of the polymer. 

Potentiometric and H-NMR methods were combined in the studies of the interaction of [Pd(en)(H20)2]2+ and [Pd(pic)(H20)2]2+ (pic = 2-picolylamine) with monodentate ligands containing nitrogen or sulfur donor atoms. The ligands represent the side chain residues of nucleic acids and proteins.178... 

Clementi, E. Structure of water and counterions for nucleic acids in solution , in Structure and Dynamics Nucleic Acids and Proteins, Clementi, E., Sarma, R. H. (eds.), New York, Adeline Press 1983... 

Hall IH, Liou YF, Lee KH. Antitumor agents LII The effects of molephantinin on nucleic acid and protein synthesis of Ehrlich ascites cells. J Pharm Sci 1982 71 687-690. 

The complete complex of nucleic acid and protein, packaged in the virus particle, is called the virus nucleocapsid. Although the virus structure just described is frequently the total structure of a virus particle, a number of animal viruses (and a few bacterial viruses) have more complex structures. These viruses are enveloped viruses, in which the nucleocapsid is enclosed in a membrane. Virus membranes are generally lipid bilayer membranes, but associated with these membranes are often virus-specific proteins. Inside the virion are often one or more virus-specific enzymes. Such enzymes usually play roles during the infection and replication process. 

Assembly of nucleic acid and protein subunits (and membrane components in enveloped viruses) into new virus particles ... 

Virus infection obviously upsets the regulatory mechanisms of the host, since there is a marked overproduction of nucleic acid and protein in the infected cell. In some cases, virus infection causes a complete shutdown of host macromolecular synthesis while in other cases host synthesis proceeds concurrently with virus synthesis. In either case, the regulation of virus synthesis is under the control of the virus rather than the host. There are several elements of this control which are similar to the host regulatory mechanisms, but there are also some uniquely viral regulatory mechanisms. We discuss various regulatory mechanisms when we consider the individual viruses later in this chapter. 

It should already be clear from what has been stated that a great diversity of viruses exist. It should therefore not be surprising that there is also a great diversity in the manner by which virus multiplication occurs. Interestingly, many viruses have special features of their nucleic acid and protein synthesis processes that are not found in cells. In the present chapter, we are only able to present some of the major types of virus replication patterns, and must skip some of the interesting exceptional cases. 

The analysis of extraterrestrial matter is concentrated on the detection of nucleic acid and protein building blocks, i.e., N-heterocycles and amino acids. The search for such compounds began immediately after the fall of the Murchison meteorite. Twenty-two amino acids were detected in it as early as 1974 eight of them pro-teinogenic, ten which hardly ever occurred in biological material, and four which were unknown in the biosphere. Up to now, about 70 amino acids have been identified (Cronin, 1998), the most common being glycine and a-aminoisobutyric acid. The latter is a branched-chain amino acid with the smallest possible number of carbon atoms. The most frequently found amino acids occur in concentrations of... 

In today s discussion of the origin of life, the RNA World (Chapter 6) is seen as much more important, and is much better publicized, than the protein world . However, nucleic acids and proteins are of equal importance for the vital metabolic functions in today s life forms. Peptides and proteins are constructed from the same building blocks (monomers), the aminocarboxylic acids (generally known simply as amino acids). The way in which the monomers are linked, the peptide bond, is the same in peptides and proteins. While peptides consist of only a few amino acids (or to be more exact, amino acid residues), proteins can contain many hundreds. The term protein (after the Greek proteuein, to be the first) was coined by Berzelius in 1838. 

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