CONSTRUCTING OPTIMAL BACKBONE SEGMENTS FOR JOINING FIXED DNA-BASE PAIRS

A method is presented to link a sequence of space-fixed base pairs by the sugar-phosphate segments of single nucleotides and to evaluate the effects in the backbone caused by this positioning of the bases, The entire computational unit comprises several nucleotides that are energ y-minimized, subject to constraints imposed by the sugar-phosphate bac kbone segments being anchored to space-fixed base pairs, The minimizat ion schemes are based on two stages, a conjugate gradient method follo wed by a Newton-Raphson algorithm. Because our purpose is to examine t he response, or relaxation, of an artificially stressed backbone, it i s essential to be able to obtain, as closely as possible, a lowest min imum energy conformation of the backbone segment in conformational spa ce, For this purpose, an algorithm is developed that leads to the gene ration of an assembly of many local energy minima. From these sets of local minima, one conformation corresponding to the one with the lowes t minimum is then selected and designated to represent the backbone se gment at its minimum. The effective electrostatic potential of mean fo rce is expressed in terms of adjustable parameters that incorporate so lvent screening action in the Coulombic interactions between charged b ackbone atoms; these parameters are adjusted to obtain the best fit of the nearest-neighbor phosphorous atoms in an x-ray structure.