Three-dimensional model and molecular dynamics simulation of the active site of the self-splicing intervening sequence of the bacteriophage T4 nrdB messenger RNA.

The secondary and 3D structure of the active site of the self-splicing T4 nrdB RNA has been modeled on a graphics workstation by use of the suggested 3D arrangement of the active site of the Tetrahymena IVS [Kim, S.H., & Cech, T.R. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8788-8792] as a guideline. The initially obtained crude structure was then subjected to molecular mechanics energy minimization and molecular dynamics simulation to relax tensions. In this process the energy decreased considerably and gave a final structure that deviated by 3 A [root mean square (rms)] from the initial structure. The cofactor guanosine (and the competitive inhibitor arginine) was docked to a proposed [Michel, F., Hanna, M., Green, R., Bartel, D.P., & Szostak, J.W. (1989) Nature 342, 391-395] binding site, where it was found to fit rather well. A minor modification of the binding mode easily brought the O3' end of the guanosine within 2 A of the phosphodiester bond where the primary cleavage occurs.