COMPUTER-SIMULATION OF PROTEIN-INDUCED STRUCTURAL-CHANGES IN CLOSED CIRCULAR DNA

The effect of protein-induced wrapping on overall DNA folding is studi ed using Monte Carlo computer simulation techniques. A new modeling sc heme is devised to represent configurations of closed circular DNA con taining fragments of the double helix partially wrapped around a core of proteins. The DNA consists of two regions, a fragment wrapped in a left-handed superhelical path around a 'phantom' protein core and a fr ee connecting loop. The loop has at least one single-stranded scission so that it can assume a torsionally relaxed state. The configuration of the loop is varied during the course of the computer simulations an d the three-dimensional spatial arrangements of lowest total energy ar e identified. The axis of the DNA loop is represented by a finite thre e-dimensional Fourier series perturbation of an initial Bezier curve, making it possible to fix the position and orientation of the chain en ds as well as the contour length of the free loop. The energy is appro ximated by elastic terms for the bending and twisting of the DNA and a n excluded volume contribution that prevents the self-intersection of sequentially distant chain segments. The proportions of the protein-DN A complex, the number of superhelical turns, the chain length and the imposed linking: number difference of the closed DNA are varied in the calculations. The resulting minimum energy structures are consistent with physical models and suggest new ways to think about how proteins add and remove supercoils from DNA. Of special note in this regard is the sudden collapse of three-dimensional structure that accompanies sm all incremental wrapping of the DNA around the idealized protein core. These observations offer new structural insight into the mechanisms o f action of proteins which add or remove supercoils from DNA and provi de a fir st step in thinking about the activity of such systems at the chemical level whereby small fluctuations in local molecular structur e are translated into large-scale macromolecular changes. The configur ations identified in the simulations can also be examined in the conte xt of the well known ''linking number paradox'' associated with nucleo some formation on closed circular plasmids. The findings bear relevanc e to DNA with natural curvature as well as to protein-induced bending and deformations of the double helix.