DNA STRUCTURE AND PROTEIN-DNA INTERACTIONS. C.R. Calladine, Department of Engineering, University of Cambridge, Cambridge CB2 1PZ, UK

When protein binds to DNA, the DNA is sometimes distorted and sometimes not: evidently the deformability of DNA is a feature of the recognition process. What is the general nature of distortion of and within DNA? And how does the presence of a protein impose such distortion? Now, the various components of DNA are connected together in a well-known way : the base-pairs stack onto each other, and they are connected to the double-helical backbones. The local and global conformation of the molecule may be described by means of a large number of geometric parameters; and in general the values of these must change when the conformation alters. But what are the physically important features of these geometric changes?

In this talk I shall examine the stacking preferences of the 10 different dinucleotide steps by sequence (mainly by a detailed inspection of the variety of step conformations found in a crystallographic database) and show how these relate to larger-scale geometric features of the DNA such as curvature, twist and the widths of the major and minor grooves. I shall also examine the systems of constraint that are necessary in order to "dock" a protein onto a piece of DNA so that the protein side-chains may "probe" the details of the bases concerned. This will include a discussion of the role of "flexible" protein moieties in the business of recognition.

References

1. C.R. Calladine & H.R. Drew. Understanding DNA. Academic Press 1992.

2. M.A. El Hassan & C.R. Calladine. J. Mol. Biol. (1995) 251, 648-664; and in press.