A USEFUL ROLE FOR STATIC MODELS IN ELUCIDATING THE BEHAVIOR OF DNA INSOLUTION

Double-helical DNA is a long and flexible molecule that is in constant motion under thermal perturbations, more so in solution than in the c rystal. Some workers, for example Olsen et al., have argued that the b ehaviour of this molecule in assays such as circularization or gel ele ctrophoresis can only be understood properly by means of theories that take full account of its dynamical nature due to thermal motions. Oth er workers, per contra, have claimed success at explaining aspects of the behaviour of DNA in solution by means of ''static'' models that fo cus on ''time-averaged'' conformations. In these static models, the in trinsic curvature of DNA and its flexibility are both related to seque nce-dependent base-stacking effects, that are susceptible to study by the inherently static tools of X-ray crystallography and electron micr oscopy. Here we examine the question of whether such static models can , in practice, provide a clear understanding of what are generally ack nowledged to be dynamic phenomena. Our investigation discusses some ge neral principles of scientific method, and how suitable conceptual mod els are chosen; it describes the basic concept of ''persistence length '', and argues that long, superhelical DNA may be regarded at once as locally stiff yet globally flexible; it cites experimental evidence on gel-running which suggests that the flexibility of the molecule is no t a crucial factor in relation to its mobility in electrophoretic gels ; and it summarizes many data from gel-running, X-ray crystallography and electron microscopy, all of which provide a similar picture of DNA in solution as a stable, sequence-dependent polymer. Therefore, our i nvestigation dearly favours the use of static models to explain many i mportant aspects of the behaviour of DNA in solution; while it accepts the use of ''dynamic'' models in certain specific cases, such as the kinetics of circularization, where the rate-limiting step is a high-en ergy thermal vibration away from the most-stable structure. (C) 1996 A cademic Press Limited