Double helix molecular modeling

Primary and Secondary Structure. The DNA double helix was first identified by Watson and Crick in 1953 (4). Not only was the Watson-Crick model consistent with the known physical and chemical properties of DNA, but it also suggested how genetic information could be organized and rephcated, thus providing a foundation for modem molecular biology. 

Extrapolation of the molecular structure of an a-maltohexaose duplex com-plexed with triiodide in single crystals leads to a left-handed, 8-fold, antiparallel double-helix for amylose.90 The pitch of this idealized helix is 18.6 A, so h is only 2.33 A. Although this model is no contender to the fiber data, in terms of biosynthesis, it is doubtful that the native amylose helix favors antiparallel chains. 

The fourth is a cube synthesized by Chen and Seeman, the components of which are based upon DNA (Fig. 9.12c). [35] The directionality and ability of the double helix to form branched junctions are exploited for the edges and vertices, respectively. Interestingly, each face of this molecule forms a cyclic strand which is catenated with strands of adjacent faces. Molecular modeling experiments indicate the length of each edge to be approximately 6.8 nm. 

Using the pitch, symmetry, monomer geometries and other stereochemical constraints, a number of types of molecular model can be constructed. Typical dilemmas are whether the molecular helix is left- or right-handed, whether the molecule is a single helix or coaxial double-helix (and in the later case whether the two chains in the duplex are parallel or antiparallel), or whether, if there are two or more molecules in the unit cell, the molecules are parallel or antiparallel. Solution of a structure therefore involves refinement and adjudication All candidate models are refined until the fit with the measured x-ray amplitudes or steric factors allows one model to be declared significantly superior to the others by some standard statistical test. 

For quantitative structure-activity relationship (QSAR) studies a three-dimensional model of a DNA-quinoIone complex was built using molecular modeling techniques. It was based on the intercalation of quinolone into the double helix of DNA. It was concluded that the intercalation model is consistent with most available data on the structure of the quinolone complex. This predicted... 

Front cover illustration A DNA double helix chemically modified at the N2 of a guanine residue to possess a y-aminobutyric acid (GABA) group. The molecular model was kindly provided by Dr. George Pack of the University of Illinois College of Medicine at Rockford. 

In the case of 10-fold helices, the two chains in a double helix would be related by 2-fold symmetry coincident with the helix axis. Starting from several grid points, the intra-and inter-molecular short contacts within a double helix were minimized. Only the double helix model with 10 chains could be constructed without any fatal contacts. However, we could not pack this model successfully in the unit cell because of the large helical radii for several atoms. The results of these calculations are summarized in Table II. 

In 1953, Watson and Crick proposed a three-dimensional structure of DNA which is a cornerstone in the history of biochemistry and molecular biology. The double helix they proposed for the secondary structure of DNA gained immediate acceptance, partly because it explained all known facts about DNA, and partly because it provided a beautiful model for DNA replication. 

From a chemical perspective, the double-helix produced by two intertwining strands of oligomeric DNA is a fascinating and unique molecular structure. (See Fig. 1 for a structural model of a 12-base pair duplex of B-form DNA.) In it nucleic acid bases are stacked in pairs one on top of the other with a slight twist reminiscent of a spiral staircase [16]. The unique stacking and overlapping of the n- and Tr-electrons of DNA bases may provide a preferred path for electron transfer. Similarly, the exceptional closeness of the stacked bases may have important consequences for charge motion in DNA duplexes. Additionally, the... 

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