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We present a computational method to analyze the propensity of superhelically stressed DNA to undergo strand separation events, as is required for the initiation of both transcription and replication. We build in silico models to analyze the statistical mechanical equilibrium distribution of a population of identical, stressed DNA molecules among its states of strand separation. In this phenomenon, which we call stress induced duplex destabilization (SIDD), a state energy is determined by the energy cost of opening the specific separated base pairs in that state, and the energy relief from the relaxation of stress this affords. We use experimentally measured values of all energy parameters, including the nearest neighbor energetics known to govern DNA base pair stability. We perform a statistical mechanical analysis in which the approximate equilibrium distribution is calculated from all states whose free energies do not exceed a user-defined threshold. This provides the most general and efficient computational approach to the analysis of this phenomenon. The algorithm is implemented in C++.
Date of Conference: 11-14 Aug. 2003