A useful role for ''static'' models in elucidating the behaviour of DNA in solution

Double-helical DNA is a long and flexible molecule that is in constant motion under thermal perturbations, more so in solution than in the crystal. Some workers, for example Olsen et al., have argued that the behaviour of this molecule in assays such as circularization or gel electrophoresis can only be understood properly by means of theories that take full account of its dynamical nature due to thermal motions. Other workers, per contra, have claimed success at explaining aspects of the behaviour of DNA in solution by means of ''static'' models that focus on ''time-averaged'' conformations. In these static models, the intrinsic curvature of DNA and its flexibility are both related to sequence-dependent base-stacking effects, that are susceptible to study by the inherently static tools of X-ray crystallography and electron microscopy. Here we examine the question of whether such static models can, in practice, provide a clear understanding of what are generally acknowledged to be dynamic phenomena. Our investigation discusses some general principles of scientific method, and how suitable conceptual models 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 not 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 investigation dearly favours the use of static models to explain many important 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-energy thermal vibration away from the most-stable structure. (C) 1996 Academic Press Limited