Nucleic models

Mathematical Model of the Nucleic Acids Conformational Transitions with Hysteresis over Hydration-Dehydration Cycle... 

Abstract. A model of the conformational transitions of the nucleic acid molecule during the water adsorption-desorption cycle is proposed. The nucleic acid-water system is considered as an open system. The model describes the transitions between three main conformations of wet nucleic acid samples A-, B- and unordered forms. The analysis of kinetic equations shows the non-trivial bifurcation behaviour of the system which leads to the multistability. This fact allows one to explain the hysteresis phenomena observed experimentally in the nucleic acid-water system. The problem of self-organization in the nucleic acid-water system is of great importance for revealing physical mechanisms of the functioning of nucleic acids and for many specific practical fields. 

Taking into account the hydration shell of the NA and the possibility of the water content changing we are forced to consider the water -I- nucleic acid as an open system. In the present study a phenomenological model taking into account the interdependence of hydration and the NA conformation transition processes is offered. In accordance with the algorithm described above we consider two types of the basic processes in the system and thus two time intervals the water adsorption and the conformational transitions of the NA, times of the conformational transitions being much more greater... 

The NAs such as DNA usually used in the experiments consist of 10" -1 o nucleotides. Thus, they should be considered as macrosystems. Moreover, in experiments with wet NA samples macroscopic quantities are measured, so averaging should also be performed over all nucleic acid molecules in the sample. These facts justify the usage of the macroscopic equations like (3) in our case and require the probabilities of finding macromolecular units in the certain conformational state as variables of the model. 

Some aspects, such as the computer representation and manipulation of proteins and nucleic acids, could not be covered. Even the modeling of the interactions of small molecules with proteins, as dealt with in docking software or software for de novo design could not be included in the Textbook, although chapters in the Handbook do treat these subjects. 

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.)... 

The AMBER (Assisted Model Building and Energy Refin emeni) is based on a force field developed for protein and nucleic acid computations by members of the Peter Kollman research group at the... 

Darden T A, L Perera, L Li and L Pedersen 1999. New Tricks for Modelers from the Crystallography Toolkit The Particle Mesh Ewald Algorithm and Its Use in Nucleic Acid Simulations. Structure with Folding and Design 7 R55-R60. 

Assisted model building with energy refinement (AMBER) is the name of both a force field and a molecular mechanics program. It was parameterized specifically for proteins and nucleic acids. AMBER uses only five bonding and nonbonding terms along with a sophisticated electrostatic treatment. No cross terms are included. Results are very good for proteins and nucleic acids, but can be somewhat erratic for other systems. 

In computational chemistry it can be very useful to have a generic model that you can apply to any situation. Even if less accurate, such a computational tool is very useful for comparing results between molecules and certainly lowers the level of pain in using a model from one that almost always fails. The MM+ force field is meant to apply to general organic chemistry more than the other force fields of HyperChem, which really focus on proteins and nucleic acids. HyperChem includes a default scheme such that when MM+ fails to find a force constant (more generally, force field parameter), HyperChem substitutes a default value. This occurs universally with the periodic table so all conceivable molecules will allow computations. Whether or not the results of such a calculation are realistic can only be determined by close examination of the default parameters and the particular molecular situation. ... 

One important class of integral equation theories is based on the reference interaction site model (RISM) proposed by Chandler [77]. These RISM theories have been used to smdy the confonnation of small peptides in liquid water [78-80]. However, the approach is not appropriate for large molecular solutes such as proteins and nucleic acids. Because RISM is based on a reduction to site-site, solute-solvent radially symmetrical distribution functions, there is a loss of infonnation about the tliree-dimensional spatial organization of the solvent density around a macromolecular solute of irregular shape. To circumvent this limitation, extensions of RISM-like theories for tliree-dimensional space (3d-RISM) have been proposed [81,82],... 

Central to the quality of any computational smdy is the mathematical model used to relate the structure of a system to its energy. General details of the empirical force fields used in the study of biologically relevant molecules are covered in Chapter 2, and only particular information relevant to nucleic acids is discussed in this chapter. 

The second generation force fields for nucleic acids were designed to be used with an explicit solvent representation along with inclusion of the appropriate ions [28,29]. In addition, efforts were made to improve the representation of the conformational energetics of selected model compounds. Eor example, the availability of high level ab initio calculations on the conformational energetics of the model compound dimethylphosphate yielded... 

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