WHAT BASE PAIRINGS CAN OCCUR IN DNA - A DISTRIBUTED MULTIPOLE STUDY OF THE ELECTROSTATIC INTERACTIONS BETWEEN NORMAL AND ALKYLATED NUCLEIC-ACID BASES

Ab initio distributed multipole electrostatic calculations are used to predict likely nucleic acid base pair structures for both the gas pha se and within a double helical backbone, as represented by simple cons traints. The resulting structures are interpreted by comparison with a n analysis of the experimental variation of base pair geometries found in oligonucleotide crystals. Our calculations on all pairs of the nor mal bases (G, A, T, C) correctly predict all the multiply hydrogen-bon ded structures, in agreement with supermolecule SCF calculations, and also predict some new low-energy structures. Consideration of the heli cal constraints confirms that the Watson-Crick G . C and A . T pairing s are most favourable for inclusion in DNA, but certain mismatch base pairs, G . T and G . A, are also energetically favourable and their ge ometries correspond to the experimentally observed wobble conformation s. This approach is also used to study the effect of the O6 methylatio n of guanine which can form a doubly hydrogen-bonded Watson-Crick-like structure with thymine. However, there are also a range of O6-methylg uanine . cytosine structures which fit into the helical backbone and a re energetically competitive. Thus the mutation-inducing effects of th is base modification are likely to be very sensitive to the exact sequ ence and local conformation of the DNA.