RNA LOOP STRUCTURE PREDICTION VIA BOND SCALING AND RELAXATION

We have developed a method for predicting the structure of small RNA l oops that can be used to augment already existing RNA modeling techniq ues. The method requires no input constraints on loop configuration ot her than end-to-end distance. Initial loop structure are generated by randomizing the torsion angles, beginning at one end of the polynucleo tide chain and correlating each successive angle with the previous. Th e bond lengths of these structures are then scaled to fit within the k nown end constraints and the equilibrium bond lengths of the potential energy function are scaled accordingly. Through a series of rescaling and minimization steps the structures are allowed to relax to lower e nergy configurations with standard bond lengths and reduced van der Wa als clashes. This algorithm has been tested on the variable loops of y east tRNA-Asp and yeast tRHA-Phe, as well as the sarcin-ricin tetraloo p and the anticodon loop of yeast tRNA-Phe. The results indicate good correlation between potential energy and the loop structure prediction s that are closest to the variable loop crystal structures, but poorer correlation for the more isolated stem loops. The number of stacking interactions has proven to be a good objective measure of the best loo p predictions. Selecting on the basis of energy and stacking, we obtai n two structures with 0.65 and 0.75 Angstrom all-atom rms deviations ( RMSD) from the crystal structure for the tRNA-Asp variable loop. The b est structure prediction for the tRNA-Phe variable loop has an all-ato m RMSD of 2.2 Angstrom and a backbone RMSD of 1.6 Angstrom, with a sin gle base responsible for most of the deviation. For the sarcin-ricin l oop from 28S ribosomal RNA, the predicted structure's all-atom RMSD fr om the nmr structure is 1.0 Angstrom. We obtain a 1.8 Angstrom RMSD st ructure for the tRNA-Phe anticodon loop. (C) 1996 John Wiley & Sons, I nc.