Nucleic quantum-mechanical calculations

This paper presents quantum mechanical studies of the, 5N and, 3C chemical shifts in both the N7-H and N9-H tautomeric forms of purine. Quantum mechanical calculations of the chemical shifts were used to assign the NMR resonances and the spatial orientation of the principal axes of the chemical shift tensors. Calculations in purine and in a pyridine-methanol complex model provide insights on the importance of the intermolecular interactions on the chemical shifts of the nucleic acid bases. 

The polysaccharides are, after the proteins and the nucleic acids, the third important group of biological polymers. From the point of view of the quantum-mechanical calculations of their conformational problems, mention may be made in the first place of the work of Neely 13> who has studied by the Extended Hiickel Theory the relative conformational stabilities of a few of the different possible chair and boat conformations of D-glucose, II. Within the conformations studied, the chair one, known under the designation Cl, appears so far the most stable. Experimentally, it is apparently the most stable of all. Moreover, the (3-anomer comes out as 9 kcal/mole more stable than the a-one. Although this difference is far too large with respect to experiment, it is in the proper direction. 

It is essential to stress that our present theoretical knowledge about the electronic properties of the nucleic acids and their constituents arises from many calculations carried out by different techniques, and that although the exact values of the calculated electronic indices depend, of course, on the particular method utilized, the comparison of the different results clearly shows that they all lead to substantially the same conelusions in so far as the general aspects of the electronic structure are concerned. In particular, the calculations make possible, naturally, the determination of the sites at which the different indices have their most significant values. This is, frequently, one of the most important aspects of the results, because this determination enables one to locate the essential sites associated with the eorresponding physico-chemical properties of the nucleic acids. Now, all the methods so far utilized for quantum-mechanical calculations on the nucleic bases or base pairs definitely lead to practically the same conclusions in this respect. These... 

At this point (early 1980s) it became clear that we really needed to divide the treatment of aromatic heterocycles into two different, general cases. The first case is ordinary heterocyclic molecules. For those, the calculations are carried out as previously described. The second case would be when we wished to carry out a calculation on a macromolecule such as DNA, which has a great many molecules of nucleic acid bases present, and we do not want to do a quantum mechanical calculation on each of them one by one. We wished to carry out the quantum mechanical calculation for a given base once, and then develop a force field that will reproduce the structure of each of these bases adequately. These molecular force fields are then stored in a library. For future calculations involving those molecules then, one obtains from the library the appropriate force field for each of those molecules as needed, and they are then used in the ordinary molecular mechanical manner. 

When we became seriously concerned about this problem (about 1985 ), it could not be convincingly decided which of these basic alternatives was correct (Hartree-Fock or X-ray), and it was not possible to proceed further. Subseqently, however, computers developed to the point where it became possible to carry out what are now considered modest quantum mechanical calculations directly on the nucleic acid base molecules. When this was done, it was found that the main problem did not lie in the molecular mechanics approximations themselves, nor did it lie in the experimental comparison of a crystal stracture with a gas-phase structure. Rather, the major problem... 

The parameters have been determined to reproduce energetic, structural and dynamic properties found from ab initio quantum mechanical calculations, spectroscopic measurements, and crystallographic data. Partial charges have been derived once for each atom type and they are independent of the actual chemical environment of atoms. Such an approach produces a transferable set of charges for standard components of the proteins and nucleic acids. Derivation of a charge model for a new system is based on quantum mechanical calculations. 

Significant progress in the optimization of VDW parameters was associated with the development of the OPLS force field [53]. In those efforts the approach of using Monte Carlo calculations on pure solvents to compute heats of vaporization and molecular volumes and then using that information to refine the VDW parameters was first developed and applied. Subsequently, developers of other force fields have used this same approach for optimization of biomolecular force fields [20,21]. Van der Waals parameters may also be optimized based on calculated heats of sublimation of crystals [68], as has been done for the optimization of some of the VDW parameters in the nucleic acid bases [18]. Alternative approaches to optimizing VDW parameters have been based primarily on the use of QM data. Quantum mechanical data contains detailed information on the electron distribution around a molecule, which, in principle, should be useful for the optimization of VDW... 

A number of tautomeric forms of some fundamental purines have been studied quantum mechanically with the help of the standard, semiempirical Hiickel approximation of the molecular orbital method.57 58 Limited to ti electrons, these studies nevertheless enabled the determination of a number of electronic differences among the tautomers. Using some simplifying ideas, typical in 77-electron calculations, information has also been obtained, within the limits of this approximation, concerning the relative tendencies of the bases to undergo a given type of tautomerization, and this information has been used successfully for the prediction of the preferential mutagenic sites in the nucleic acids.50... 

Similar interactions have been observed in small-molecule nucleic acid crystal structures (see Fig. 7), and enthalpies of between -1.1 and -2.3 kcal/mol have been calculated for these cases by ab initio quantum mechanical methods (Amidon et al., 1975). 

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