Base-pair specificity of protein-DNA recognition: a statistical-mechanical model.

The statistics of base-pair choice in individual recognition sites on DNA is shown to be determined by the functional binding requirements for recognition and a selection parameter. This selection parameter can be identified as a generalized external force required to deform a random-choice base-pair distribution into the observed specific-choice distribution. This external force is balanced by the randomization pressure which--driven by mutations--always tends to increase randomness in the base-pair choices. The model makes it possible to predict relative binding constants of particular recognition sequences based primarily on the statistics of base-pair usage. A further consequence of this formulation is that the randomization pressure appears explicitly as an important force shaping the evolutionary selection not only of DNA sites, but also of other properties involving macromolecular design.