Conformational states governing the rates of spontaneous transition mutations

We report the results of a theoretical study, combining the results of sequence analysis and integral equation structural methods for nucleic acids in aqueous solutions, on the effects of nearest neighbors on the (T.G) mispair in solution, for 12 nearest neighbor contexts. Attempts have been made to classify the structural and energetic effects of the 5′ and 3′ neighbors with respect to the observed spontaneous mutation rates in vertebrates. It is found that 5′ nearest neighbor is probably the most critical structural factor in facilitating or discouraging mutations. Local conformational states correlate with discrimination of bases to be excised in mispairs. Our study confirms the role of the flexibility of the DNA molecule in governing the rates of spontaneous mutations. © 1995 John Wiley & Sons, Inc.