No abstract

We have developed a computer modeling protocol that can be used to predict the three-dimensional folding of a ribonucleic acid on the basis of limited amounts of secondary and tertiary data. This protocol extends the use of distance geometry beyond the domain of NMR data in which it is usually applied. The use of this algorithm to fold the molecule eliminates operator subjectivity and reproducibly predicts the overall dimensions and shape of the transfer RNA molecule. By use of a replacement pseudoatom set based on helical substructures, a series of transfer RNA foldings have been completed that utilize only the primary structure, the phylogenetically deduced secondary structure, and five long-range interactions that were determined without reference to the crystal structure. In a control set of foldings, all the interactions suspected to exist in 1969 have been included. In all cases, the modeling process consistently predicts the global arrangement of the helical domains and to a lesser extent the general path of the backbone of transfer RNA.

The rapid advances in computer graphics and in the power and affordability of computers provide us with an opportunity to develop an objective, reproducible, and flexible modeling procedure which is superior to the physical modeling techniques now in use. It was the goal of this research to develop and implement a rational modeling protocol which could be applied to the folding of 16S ribosomal RNA.Modeling of a DNA dodecamer and comparison with the structures of the molecule obtained by NMR and X-ray crystallography reaffirm that the results obtained by modeling are dependent on the input data set. Energy minimization produces a final structure which 14