MODELING PROTEIN-INDUCED CONFIGURATIONAL CHANGES IN DNA MINICIRCLES

A method is offered for obtaining minimum energy configurations of DNA minicircles constrained by one or more DNA-binding proteins. The mini circles are modeled as elastic rods, while the presence of bound prote in is implied by rigidly fixing portions of these chains. The configur ations of the geometrically constrained circular rods are sampled stoc hastically and optimized according to a simple elastic energy model of nicked DNA. The shapes of the minimum energy structures identified af ter a simulated annealing process are analyzed in terms of relative pr otein orientation and writhing number. The procedure is applied to min icircles 500 base pairs in length, bound to two evenly spaced DNA-wrap ping proteins. The presence of histone octamers is suggested by rigidl y fixing the two protein-bound portions of each minicircle as small su perhelices similar in dimension to nucleosomal DNA. The folded minimum energy forms of sample chains with different degrees of protein wrapp ing are noteworthy in themselves in that they offer a new resolution t o the well-known minichromosome linking number paradox and point to fu ture minicircle simulations of possible import. (C) 1997 John Wiley & Sons, Inc.