The goal of this research is the development of computer-based models for investigating the influence of DNA sequence on the structure and dynamics of the molecule. Methods to be used include conformational energy calculations, molecular dynamics, normal mode analysis, and computer graphics, including real-time movies. The motions to be studied range from the rapid fluctuations of local structure, such as backbone torsional angles and sugar pucker, to the slower variations of large scale structure, such as bending, twisting, stretching, and breathing of the helix. Correlations between these motions will be investigated, as will their variation as a function of conformation (A-DNA, B-DNA, and Z-DNA). Transitions between the various conformations will also be examined. In all of the foregoing studies, investigations are to be made into the effects of sequence and chemical modification of the bases. This research will lead to an understanding of how sequence determines structure, laying some of the groundwork for research into the problem of how proteins recognize specific DNA sequences, a fundamental problem in understanding the regulation of gene replication and expression.
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