Prediction of DNA structure from sequence: A build-up technique

A build‐up technique has been devised that permits prediction of DNA structure form sequence. No experimental information is employed other than the force field parameters. This strategy for dealing with the multiple minimum problem requires a supercomputer to make the necessary global searches. The number of energy minimization trials that were made for each of the 16 deoxydinucleoside monophosphate conformational building blocks of DNA was 1944. As a test case, the minimum energy conformations of d(GpC) and d(CpG) to 5.5 kcal/mole were then combined to generate energy‐minimized structures for d(CpGpC). The number of trials that were made for d(CpGpC) was 3752. Minima for this single‐stranded trimer to 15 kcal/mole were then employed to search for minimum energy conformations of the duplex d(CpGpC) · d(GpCpG). The number of starting conformations that were utilized at this stage was 1514. The lowest energy duplex had a Z‐II‐DNA conformation, followed by a B‐DNA form at 1.2 kcal/mole. The A‐ and Z‐I‐forms as well as many novel Watson–Crick base‐paired structures were found at higher energy. Finally, energy‐minimized structures of d(CG)6 in Z‐II and B‐DNA conformations were computed using torsion angles from the analogous duplex trimer minima.